MRx Pipeline October

Table of CONTENTS

EDITORIAL STAFF

Maryam Tabatabai, PharmD Editor-in-Chief Vice President, Clinical Information Carole Kerzic, RPh Executive Editor Drug Information Pharmacist

Consultant Panel

Daphne Atria, PharmD, BCPS, CPE Strategic Clinical Pharmacist Consultant Michelle Booth, PharmD Director, Specialty Clinical Solutions Chelsea Fischer, PharmD Specialty Drug Information Pharmacist Robert Greer, RPh, BCOP Vice President, Clinical Strategy and Programs Katie Lockhart Manager, Forecasting and Pharmacoeconomics Simone Ndujiuba, PharmD, BCOP Director, Clinical Strategy and Innovation, Oncology

Nothing herein is or shall be construed as a promise or representation regarding past or future events and Magellan Rx Management expressly disclaims any and all liability relating to the use of or reliance on the information contained in this presentation. The information contained in this publication is intended for educational purposes only and should not be considered clinical, financial, or legal advice.  By receipt of this publication, each recipient agrees that the information contained herein will be kept confidential and that the information will not be photocopied, reproduced, distributed to, or disclosed to others at any time without the prior written consent of Magellan Rx Management.

Editor-in-Chief's MESSAGE

Welcome to the MRx Pipeline. This quarterly publication offers clinical insights and competitive intelligence on anticipated drugs in development, so you are well-sourced on the drug pipeline.

MRx Pipeline, our universal forecast, addresses trends applicable across market segments. Traditional and specialty drugs as well as agents under the pharmacy and medical benefits are featured. Also profiled in the report are new molecular entities, pertinent new and expanded indications for existing medications, and biosimilars.

Clinical analyses, financial outlook, and pre-regulatory status are considered. The products housed in the MRx Pipeline have been researched in detail. They have been developed in consultation with our internal team of clinical and analytics experts.

METHODOLOGY

Emerging therapeutics continue to grow and influence the clinical and financial landscape. Therefore, Magellan Rx Management has developed a systematic approach to determine the products with significant clinical impact. For the in-depth clinical evaluations, the products’ potential to meet an underserved need in the market by becoming the new standard of care, and the ability to replace existing therapies were investigated. The extent to which the pipeline drugs could shift market share on a formulary and their impact on disease prevalence were also important considerations.

In order to assist payers with assessing the potential impact of these pipeline drugs, where available, a financial forecast has been included for select products. Primarily complemented by data from EvaluateTM, this pipeline report looks ahead at the 5-year projected annual US sales through the year 2026. These figures are not specific to a particular commercial or government line of business; rather, they look at forecasted total US sales. Depending on a variety of factors, including the therapeutic categories, eventual FDA-approved indications, populations within the plan, and other indices, the financial impact could vary by different lines of business.

REFLECTION

Thus far in 2022, the FDA has approved 28 novel drugs. There continues to be a trend for drugs approved with at least 1 of the FDA’s expedited approval methods and drugs designated as Orphan Drugs. For the remainder of the year, 20 notable drugs filed with the agency are profiled, each with an anticipated FDA decision in 2022.

ON THE HORIZON

As we look ahead, there is a continued trend towards the approval of specialty medications and drugs for rare conditions, with 68% and 41% of approvals expected, respectively, for agents with applications submitted to the FDA. There are 7 agents seeking FDA’s Accelerated Approval, which allows for earlier drug approval for serious conditions that fill an unmet need based on a surrogate endpoint reasonably likely to predict a clinical benefit. New treatments for Alzheimer’s disease and women’s health are expected. Other noteworthy pipeline trends to watch include the development of complex therapies, gene therapy, oncology, immunology, immunotherapy, and therapeutic options for ultra-rare hereditary diseases. Moreover, sprouting products for RSV and therapeutic psychedelics are being actively monitored through MRx Pipeline.

The drug pipeline ecosphere will continue to evolve as it faces challenges and successes. Innovative agents that show positive results without compromising patient safety and access offer true therapeutic advances and hold the promise to alter the treatment paradigm.

Maryam Tabatabai, PharmD Editor-in-Chief, MRx Pipeline

Objective evidence-based methodology was used to identify the Deep Dive

in the upcoming quarters. This section features a clinical overview and explores the potential place in therapy for these agents. Moreover, it addresses their FDA approval timeline and 5-year financial forecast.

PROPOSED INDICATIONS

Treatment of non-small cell lung cancer (NSCLC) harboring the Kirsten RAt Sarcoma virus (KRAS) G12C mutation after ≥ 1 prior systemic therapy

CLINICAL OVERVIEW

Adagrasib is a KRAS G12C inhibitor.

The non-randomized, open-label, phase 1/2 KRYSTAL-1 study evaluated the safety and efficacy of adagrasib in 116 patients with NSCLC and KRAS G12C mutations. Most patients (98%) had prior treatment with a PD-1/ PD-L1 inhibitor and chemotherapy. After a median follow-up of 12.9 months, adagrasib led to an ORR of 43%, DCR of 80%, median DOR of 8.5 months, and a median PFS of 6.5 months. At the January 15, 2022 cutoff, the median OS was 12.6 months. The most common TEAEs were GI events and fatigue. Among the patients, 43% experienced a grade 3/4 TEAE and 2 deaths were reported. In addition, 33 patients with previously treated stable CNS metastases were included in an exploratory, retrospective subgroup analysis. In this population, adagrasib demonstrated tumor regression based on an ORR of 33% and DCR of 85%.

Adagrasib was administered as 600 mg orally twice daily.

PLACE IN THERAPY

Lung cancer is the second most common cancer in men and women. Approximately 236,740 new cases of lung cancer are predicted to occur in the US in 2022, with approximately 130,180 deaths due to the disease. The median age at diagnosis is about 70 years. NSCLC represents 84% of all lung cancer diagnoses annually. KRAS G12C mutation is the most frequent variant in NSCLC, and it occurs in approximately 13% of lung adenocarcinomas. The KRAS G12C mutation is associated with cigarette smoking. Presence of the mutation is predictive of survival in patients with NSCLC and lack of efficacy to EGFR tyrosine kinase inhibitor (TKI) therapy (e.g., erlotinib, afatinib, gefitinib).

The oral TKI sotorasib (Lumakras®) is approved for metastatic NSLCL with KRAS G12C mutations after chemotherapy ± immunotherapy. In clinical trials, it resulted in an ORR of 37.1%, median OS of 12.5 months, and grade 3/4 TEAE rate of about 20%. The NCCN recommends sotorasib as subsequent therapy for KRAS G12C mutation-positive NSCLC.

Adagrasib also inhibits KRAS G12C mutation. In non-comparison trials, it demonstrated similar response and safety as sotorasib. Adagrasib also resulted in regression of CNS metastases with a intracranial ORR of 33% and DCR of 85%. In patients with CNS metastases, intracranial DCR of 88% (14/16) has been reported with sotorasib. If approved, adagrasib will be the second medication to treat KRAS G12C mutated NSCLC and will most likely compete with sotorasib (Lumakras) as subsequent therapy in this setting.

beremagene geperpavec topical

Krystal Biotech

PROPOSED INDICATIONS

Dystrophic epidermolysis bullosa (DEB)

CLINICAL OVERVIEW

Beremagene geperpavec (B-VEC) is a topical gene therapy. It is comprised of a non-replicating HSV-1 vector that delivers 2 copies of the COL7A1 gene directly to DEB wounds.

The double-blind, placebo-controlled, phase 3 GEM-3 trial evaluated the safety and efficacy of B-VEC in 31 patients ≥ 6 months of age with genetically confirmed DEB. At 6 months, significantly more patients treated with B-VEC achieved the primary endpoint of wound closure than those who received placebo (67.4% versus 21.6%, respectively; p<0.005). Complete healing was seen as early as 3 months (70.6% versus 19.7%, respectively; p<0.05). Treatment was not affected by baseline anti-HSV-1 serostatus or anti-collagen type VII (anti-COV7) seroconversion. B-VEC was generally well-tolerated. The most common TEAEs were pruritus and chills, each reported in 3 patients.

B-VEC was administered topically once weekly until wound closure. The maximum dose was based on the patient’s age and wound size. Treatment was restarted if reopening of wounds occurred.

PLACE IN THERAPY

Epidermolysis bullosa (EB) is a rare, inherited, genetic skin disorder characterized by formation of blisters after minor friction or trauma to the skin or mucosa. EB affects an estimated 1 in every 50,000 live births. Disease severity ranges from mild to severe disabling forms. Patients with severe EB experience lifelong painful blistering that can lead to scarring and infection. These patients are also at increased risk of aggressive squamous cell carcinoma, which typically occurs in the second decade of life and can be fatal. There is no cure for EB. Current management includes reduction of trauma to the skin and support of the patient’s nutritional needs.

DEB is a subtype of EB. It is further categorized as dominantly inherited (mild) and recessively inherited (severe) forms. DEB is caused by a defect in the COL7A1 gene that encodes the collagen type VII (COL7) protein in the fibrils that affix the dermis and epidermis layers of the skin. Notably, bone marrow transplantation and graft placement have been investigated to promote COL7 expression for recessive DEB and were associated with varying responses and mortality risks.

Topical administration of B-VEC supplies functional copies of the COL7A1 gene directly to keratinocytes and fibroblasts of the skin. If approved, it will be the first DMT available for DEB. In the phase 3 clinical trial, B-VEC demonstrated complete healing of wounds as early as 3 months; a phase 1/2 trial revealed a significant reduction in wound area at 2 months. B-VEC could provide an off-the-shelf gene-therapy in an outpatient setting that is administered during scheduled weekly dressing changes.

Two other gene therapies that target the COL7A1 gene are in late-stage development for recessive DEB. Abeona’s EB-101 is being studied as a 1-time surgical application. Phase 3 trial data is expected in 2022. Castle Creek’s dabocemagene autoficel (D-Fi) is administered via injections directly into wounds during ≥ 2 treatment sessions. D-Fi is comprised of the patient’s fibroblasts re-engineered with a full-length COL7A1 gene. Initial data for D-Fi is expected in early 2023. In addition, the FDA issued a CRL in February 2022 for Amryt’s topical 10% birch bark extract oleogel-S10 (Filsuvez) citing the need for additional clinical data.

donanemab IV

Eli Lilly

PROPOSED INDICATIONS

Early Alzheimer’s disease (AD)

CLINICAL OVERVIEW

Donanemab is a humanized immunoglobulin G1 (lgG1) antibody directed at an N-terminal pyroglutamate (N3pG) amyloid-β (Aβ) found in amyloid plaque in the brain.

The safety and efficacy of donanemab were evaluated in the randomized, double-blind, placebo-controlled, phase 2 TRAILBLAZER-ALZ trial in 257 patients ages 60 to 85 years with early symptomatic AD confirmed by the presence of tau and amyloid deposits. The primary endpoint was the change from baseline in the Integrated Alzheimer’s Disease Rating Scale (iADRS), which ranges from 0 to 144, with lower scores indicating greater cognitive and functional impairment. At 76 weeks, donanemab led to a significant 32% slowing of clinical decline compared to placebo (change in iADRS, −6.86 versus −10.06, respectively; p=0.04). Based on a hierarchy assessment, significant improvements were not observed in most secondary measures for cognitive function and ADLs. Notably, donanemab did result in a significant reduction in amyloid plaque by an average of 78% (−84.1 centiloids) at 76 weeks and 67.8% of donanemab-treated patients achieved an amyloid negative status (< 24.1 centiloids) at this time. Significant reductions in amyloid plaque were seen as early as 24 weeks (−67.8 centiloids; 40% negativity); however, no significant decrease in tau level was reported. Amyloid-related imaging abnormalities with edema or effusions (ARIA-E) occurred in 26.7% of patients treated with donanemab and 0.8% of those given placebo. ARIA-E was mostly asymptomatic and usually reported by week 12. Superficial siderosis of the CNS also occurred with donanemab (13.7% versus 3.2% with placebo).

Donanemab was administered IV every 4 weeks at a dose of 700 mg for the first 3 doses and 1,400 mg thereafter for up to 72 weeks. The dosage was adjusted based on amyloid plaque levels and occurrence of ARIA-E. Patients were switched to placebo if they achieved amyloid negativity.

PLACE IN THERAPY

AD is a neurodegenerative disorder characterized by cognitive and memory decline that is associated with impairment of ADLs and behavioral disturbances. It is the most common form of dementia. AD is estimated to affect over 5 million elderly people in the US, and its incidence is expected to nearly triple by 2060.

The presence of amyloid plaque in the brain, as well as abnormalities of cholinergic, glutamate, and serotonin systems, are thought to contribute to the development of AD. Current pharmacotherapy for mild to moderate AD includes transdermal and/or oral acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), oral N-methyl-D-aspartate (NMDA), and receptor antagonists (memantine). All single-agent products are available as generics. A fixed-dose combination of donepezil and memantine is available for moderate to severe disease. In addition, the once-monthly IV amyloid beta-directed antibody aducanumab-avwa (Aduhelm®) was granted an Accelerated Approval for the treatment of early AD in June 2021. Its FDA-approval was met with significant controversy due to uncertainty of benefit. Moreover, CMS limited coverage of aducanumabavwa to patients enrolled in clinical trials, and coverage of future anti-amyloids would also be restricted unless full approval is granted on the basis of confirmatory trials (ENVISION; primary completion, late 2025).

If approved, donanemab could be the third amyloid-targeting DMT indicated for early AD, following aducanumab-avwa and investigational lecanemab that has a FDA approval decision expected by January 6, 2023. Although lecanemab was submitted to the FDA under the Accelerated Approval program, the recently announced confirmatory trial results demonstrate clinical benefit and may support a traditional approval. While donanemab and aducanumab-avwa are administered IV every 4 weeks and require dose titration, lecanemab is dosed IV every 2 weeks at its highest dose from the start. In non-comparative clinical trials, donanemab produced greater plaque removal compared to aducanumab-avwa (−85 centiloids at 76 weeks versus −64.2 centiloids at 78 weeks, respectively). Patients who achieve an amyloid-negative status may stop donanemab therapy in as little as 6 months, a distinguishing factor from the other 2 anti-amyloid agents.

PLACE IN THERAPY cont.

is the major safety concern with anti-amyloid antibodies and may lead to dose interruption or treatment

Non-comparative trials reported ARIA-E occurred less often with donanemab (26.7%) than aducanumab-avwa (35%), but more often compared to lecanemab (9.9%).

November 2021, Eli Lilly initiated the 18-month, phase 3, head-to-head TRAILBLAZE-ALZ 4 trial comparing the plaque-clearing ability of donanemab and aducanumab-avwa in patients with early symptomatic AD.

phase 3 study of donanemab in patients with preclinical AD is also ongoing, with results expected in 2027. Other injectable anti-amyloid antibodies in late-stage development for AD include gantenerumab (SC), solanezumab (IV), and remternetug (IV, SC).

HEMATOLOGY

efanesoctocog alfa IV

Sanofi

PROPOSED INDICATIONS

Hemophilia A

CLINICAL OVERVIEW

Efanesoctocog alfa is a recombinant factor VIII (FVIII) therapy replacement product. The 52-week, open-label, phase 3 XTEND-1 study evaluated the safety and efficacy of efanesoctocog alfa in patients ≥ 12 years of age with severe hemophilia A who were previously treated with a FVIII product. The study included 2 treatment arms. In the prophylaxis arm (cohort 1; n=133) patients received efanesoctocog alfa 50 IU/kg IV once weekly for 52 weeks, and in the on-demand arm (cohort 2; n=26) patients received efanesoctocog alfa once weekly IV as needed for 26 weeks, followed by weekly prophylaxis for 26 weeks. The study met the primary efficacy endpoint of annualized bleeding rate (ABR) among patients in cohort 1. Efanesoctocog alfa prophylaxis led to a clinically meaningful reduction in bleeding as reported by a mean ABR of 0.71 (standard deviation, 1.43) and median ABR of 0.0 (interquartile range, 0.0 to 1.04). This study result was considered superior to prior FVIII prophylaxis therapy (p<0.001), a key secondary endpoint. The majority of bleeds (96.7%) that did occur resolved after a single on-demand dose of efanesoctocog alfa. At 52 weeks, statistically significant improvements were also seen in secondary endpoints for physical health, pain, and joint health among 78 patients evaluated in an intra-patient comparison of ABR with efanesoctocog alfa versus pre-study FVIII prophylaxis. The most common TEAEs were headache, arthralgia, fall, and back pain.

PLACE IN THERAPY

Hemophilia A is a congenital X-linked bleeding disorder that affects 1 in 5,000 male births. It is characterized by coagulation FVIII deficiency leading to chronic spontaneous bleeding into muscles and joints that can progress to debilitating arthropathy. The SOC is routine infusion of FVIII replacement products. Extended half-life FVIII products were designed to decrease the frequency of infusions. While longer half-lives have been achieved with crystallizable fragment (Fc) fusion (Eloctate®) and pegylation (Adynovate®, Esperoct®, Jivi®), the actual extent has been modest. Further, while the half-life of a product may be extended in adults, it is less certain in children. Individual patient response and pharmacokinetic characteristics should be considered to determine optimal dosing frequency of any product.

Efanesoctocog alfa employs Fc fusion, but differs from other increased half-life FVIII replacement products in that it is designed to prevent binding to von Willebrand factor (VWF) in circulation, resulting in a longer half-life (range, 37 to 41 hours) compared to available FVIII products. The value of efanesoctocog alfa’s long half-life was evident in the XTEND-1 trial that demonstrated meaningful protection from bleeding with once weekly dosing. In comparison, available FVIII replacement products with relatively long half-lives require twice weekly dosing. Although patient convenience is an important consideration, other product nuances should be considered when prescribing. These considerations include product purity (presence of animal-derived proteins), inhibitor development, patient pharmacokinetics, and cost. Another advancement in the hemophilia space is the SC monoclonal antibody emicizumab-kxwh (Hemlibra®), indicated for prophylaxis in hemophilia A patients with or without inhibitors. It provides dosing regimens of once every 1, 2, or 4 weeks. Gene therapy valoctocogene roxaparvovec (FDA decision expected in 2023), which offers near elimination of bleeds, and RNA interference products are also on the horizon.

If approved, efanesoctocog alfa could compete with the current FVIII replacement therapies on the market. Competition with emicizumab-kxwh (Hemlibra) may be challenging due to the latter’s SC dosing regimen as little as every 4 weeks.

PROPOSED INDICATIONS

Advanced or metastatic, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer

CLINICAL OVERVIEW

Elacestrant is an oral non-steroidal selective estrogen receptor down-regulator/degrader (SERD).

The open-label, active-controlled, phase 3 EMERALD trial evaluated elacestrant monotherapy in 477 patients with advanced or metastatic ER+/HER2− breast cancer who had progression after 1 or 2 lines of endocrine therapy and a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. Almost half of the patients enrolled (47.8%) had estrogen receptor 1 (ESR1) mutation. Patients were randomized to oral elacestrant (n=239) or investigator’s choice SOC hormonal therapy, including the estrogen receptor antagonist fulvestrant (n=165) administered IM every 28 days according to the product labeling or a once-daily oral aromatase inhibitor (AI) (n=73). At a median duration follow-up of 15.1 months, the primary endpoint of median PFS was significantly prolonged by 30% with elacestrant compared to SOC (2.8 versus 1.9 months, respectively; p=0.002) in the overall study population and by 45% (3.8 versus 1.9 months, respectively; p=0.0005) in patients with ESR1 mutation. An interim analysis revealed no significant difference in OS between the elacestrant and SOC groups in the entire study population (29.3% versus 33.2%, respectively; HR=0.75; p=0.08) and in patients with ESR1 mutations (24.3% versus 35.4%, respectively; HR=0.59; p=0.03). Nausea and vomiting were reported about twice as often with elacestrant than with SOC. The most common grade 3/4 TEAEs with elacestrant were nausea (2.5%) and back pain (2.5%). No cardiac or ocular toxicities were detected.

Elacestrant was administered as 400 mg orally once daily. A dose adjustment was permitted to manage toxicity.

PLACE IN THERAPY

Breast cancer is the second leading cancer in women in the US. It is estimated that in the US, in 2022, there will be 290,560 new cases of breast cancer diagnosed and 43,780 deaths associated with the disease.

Preferred 2nd- and later-line regimens for ER+/HER2− breast cancer are fulvestrant (Faslodex®) plus a CDK4/6 inhibitor (e.g., abemaciclib [Verzenio®], palbociclib [Ibrance®], ribociclib Kisqali®]) in patients who were not previously treated with a CDK4/6 inhibitor, and everolimus plus endocrine therapy (exemestane, fulvestrant, or tamoxifen). Other recommended regimens for 1st- and later-lines of therapy include monotherapy with fulvestrant, the selective estrogen receptor modulator (SERM) tamoxifen, or an AI (e.g., anastrozole, letrozole, exemestane).

If approved, elacestrant will be the first oral SERD indicated to treat advanced breast cancer. Elacestrant monotherapy extended the median PFS compared with SOC endocrine monotherapy, including the injectable SERD fulvestrant. Moreover, improved efficacy was seen in patients with ESR1 mutation, which signifies resistance to AIs but not to estrogen receptor (ER) inhibitors, such as SERDs. Oral elacestrant has a manageable safety profile and will most likely compete with injectable fulvestrant (Faslodex) in the 2nd- and 3rd-line settings for advanced/metastatic ER+/HER2− breast cancer.

Other oral SERDs in phase 3 trials for breast cancer include camizestrant, giredestrant, and imlunestrant.

PROPOSED INDICATIONS

Vasomotor symptoms (VMS) associated with menopause

CLINICAL OVERVIEW

Fezolinetant is a selective neurokinin-3 receptor (NK3R) antagonist. It is designed to moderate neuronal activity in the thermoregulatory center in the hypothalamus of the brain to treat menopause-related VMS.

The double-blind, placebo-controlled, phase 3 SKYLIGHT-1 and -2 trials randomized women 40 to 65 years of age with moderate to severe menopause-related VMS (≥ 7 hot flashes per day) to once daily oral fezolinetant 30 mg or 45 mg, or placebo. In SKYLIGHT-1 (n=527), fezolinetant 30 mg and 45 mg led to significant reductions from baseline in the co-primary endpoints of the reduction in the daily mean frequency of VMS at week 4 (difference from placebo, −1.87 and −2.07, respectively; p<0.001 for both) and week 12 (difference from placebo, −2.39 and −2.55, respectively; p<0.001 for both) as well as in the mean reduction in daily VMS severity at week 4 (difference from placebo, −0.15 [p=0.012] and −0.19 [p=0.002], respectively) and week 12 (difference from placebo, −0.24 [p=0.002] and −0.2 [p<0.007], respectively). The most common TEAE reported with fezolinetant 30 mg and 45 mg was headache (5.2% and 6.4%, respectively, versus 7.4% with placebo). SKYLIGHT-2 (n=484) also reported fezolinetant 30 mg and 45 mg led to significant reductions from baseline at week 12 in the primary endpoints of daily VMS frequency (difference from placebo, –6.83 and –7.5, respectively) and daily VMS severity (difference from placebo, –0.64 and –0.77, respectively). Responses were maintained at week 52 with each dose (difference from placebo: VMS frequency, –8.03 and –8.48; VMS severity, –0.83 and –0.95). In SKYLIGHT-2 both doses of fezolinetant also significantly reduced patient-reported sleep disturbance at weeks 12 and 52. In addition, topline results from the phase 3 SKYLIGHT-4 trial (n=1,800) showed that endometrial health was achieved with fezolinetant based on primary endpoint assessments of endometrial hyperplasia and endometrial cancer. Common adverse events were similar with fezolinetant and placebo.

PLACE IN THERAPY

Menopause occurs naturally at an average age of 52 years (range, 40 and 58), but can occur earlier in women who have undergone a hysterectomy or breast cancer treatment. The marked decrease in ovarian estrogen production leads to VMS, such as hot flushes (flashes) in the majority of women, which can persist for about 7 to 14 years. Moderate to severe VMS can have a strong impact on sleep and QOL. It is expected that by 2025 the global presence of postmenopausal women will be 1.1 billion.

Hormone therapy (HT) with estrogen ± progestin (in women with an intact uterus) is primarily used to alleviate hot flushes, and may also improve sleep and mood. HT formulations include commercially available oral, transdermal, topical, and vaginal products, and compounded bio-identicals. Women receiving HT can experience breast soreness, mood changes, and bloating. HT should not be used for > 5 years or in women > 60 years of age. Contraindications to HT include a history of hormone-dependent cancer, thrombosis, or stroke as well as CVD and high-risk for endometrial cancer. Non-hormonal therapies are also available for VMS, such as the SSRI paroxetine mesylate (Brisdelle®). This agent as well as off-label use of an SNRI, gabapentin, pregabalin, or clonidine are recommended in select women with moderate to severe VMS who cannot or chose not to use HT.

Fezolinetant is a first-in-class oral NK3R agonist that could offer another non-hormonal option to treat moderate to severe VMS. In clinical trials, it provided durable relief of VMS starting as early as 4 weeks. The oral dual neurokinin-1 and -3 receptor antagonist elinzanetant is also in phase 3 research for VMS.

PROPOSED INDICATIONS

Relapsed or refractory (R/R) follicular lymphoma (FL) after ≥ 2 prior systemic therapies

CLINICAL OVERVIEW

Mosunetuzumab is a CD20 x CD3 T-cell engaging bispecific antibody that targets CD3 on T cells and CD20 on tumor B cells. By binding to both cells, mosunetuzumab brings them in close proximity, allowing the patient’s existing T cells to release cytotoxic proteins and eliminate the malignant B cells.

An ongoing, open-label, single-arm, phase 2 trial is evaluating the safety and efficacy of mosunetuzumab in adults with R/R FL who had received ≥ 2 prior lines of systemic treatments, including anti-CD20 therapy and an alkylating agent. A total of 90 patients were enrolled at the data cutoff. At a median follow-up of 18.3 months, the ORR was 80%, with a complete response rate (primary endpoint) of 60%. In addition, the median PFS was 17.9 months and the median DOR was 22.8 months. The complete response rate achieved with mosunetuzumab was significantly higher compared to the 14% complete response rate seen in historical data in patients treated with the PI3K inhibitor copanlisib (p<0.0001). Cytokine release syndrome (CRS) occurred in 44% of patients who received mosunetuzumab and was chiefly grade 1/2 in severity. Grade 3/4 TEAEs occurred in 47% of patients and included neutropenia, hypophosphatemia, hyperglycemia, and anemia. No treatment-related deaths occurred.

Mosunetuzumab was administered in 21-day cycles at escalating doses during cycle 1 (1 mg on day 1, 2 mg on day 8, and 60 mg on day 15), and 30 mg for all subsequent doses. Patients who experienced a complete response received 8 cycles, and patients with a partial response or stable disease received up to 17 cycles.

PLACE IN THERAPY

FL is a slow growing (indolent) type of NHL that occurs in B-lymphocytes. FL comprises about 20% of all NHL cases. The estimated incidence of new cases is 2.6 per 100,000 individuals. There is no cure for FL. Most people live many years with chronic R/R FH (5-year OS, 90.2%). However, approximately 20% to 25% of FH cases transform to aggressive disease (e.g., DLBCL) with poor prognosis (5-year OS of 50%).

Recommended targeted options for 3rd-line or later FH therapy include copanlisib (Aliqopa®), tazemetostat (Tazverik®), and the CAR T therapies axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®).

If approved, mosunetuzumab will be the first bispecific antibody targeting CD20 (B cells) and CD3 (T cells). Moreover, this T cell-mediated therapy will be the first off-the-shelf treatment and could provide durable remission rates comparable to CAR T therapies and a lower risk of grade ≥3 CRS toxicity than CAR T products (complete response and grade ≥ 3 CRS rates, respectively: 60% and 0% with mosunetuzumab versus 60% and 8% with axicabtagene ciloleucel and 68% and 0% with tisagenlecleucel). Unlike CAR T therapies, mosunetuzumab requires > 1 dose. It is also distinguished from CAR T as it does not require the collection and genetic modification of patient cells; therefore, it has the potential for outpatient administration without the patient burden of traveling to a major academic center.

Other investigational bispecific antibodies for R/R FL include glofitamab, odronextamab, and epcoritamab. Mosunetuzumab is also in phase 3 trials for use in combination with lenalidomide (Revlimid®) for R/R FL. A SC formulation of mosunetuzumab is also being investigated.

PROPOSED INDICATIONS

Prevention of heterotopic ossification (HO; new bone formation outside of the normal skeletal system) associated with fibrodysplasia ossificans progressiva (FOP)

CLINICAL OVERVIEW

Palovarotene is a selective retinoic-acid receptor gamma (RARγ) agonist.

The ongoing, single-arm, open-label, phase 3 MOVE trial evaluated the safety and efficacy of palovarotene in patients ≥ 4 years of age with FOP. The study revealed that after 18 months of therapy, there was a 62% reduction in the primary endpoint of mean annualized change in new HO volume in patients treated with palovarotene (8,821 mm3) (n=97) compared to untreated individuals in a natural history study (23,318 mm3) (n=98) (p=0.0292). Most patients experienced ≥ 1 TEAE; 32.3% were mild, 45.5% were moderate, and 22.2% were considered severe. Premature physeal closure (PPC) or epiphyseal disorder was reported in 29.3% of patients who were skeletally immature at baseline.

The palovarotene dosage was 5 mg orally once daily administered on a continuous basis for 24 months. During HO flare-ups, the dose was increased to 20 mg once daily for 4 weeks, followed by 10 mg once daily for at least 8 weeks. In skeletal immature patients, the dose was weight-adjusted.

PLACE IN THERAPY

FOP is an ultra-rare progressive genetic disorder of the connective tissues that affects an estimated 4,000 people worldwide. In FOP, abnormal bone forms in connective tissues, such as ligaments, tendons, and skeletal muscle. This is known as heterotopic ossification (HO) and leads to significant joint immobility and disability. Beginning in early childhood, patients experience HO flares that usually occur after soft tissue injury and inflammation or a viral illness but can also occur spontaneously. FOP is caused by activating mutations in the Activin A type 1 receptor (ACVR1). The ACVR1 is involved in the bone morphogenetic protein (BMP) pathway that is essential for prenatal and lifelong skeletal formation. Inheritance of FOP is usually sporadic, but a familial pattern may be present.

There is currently no cure for FOP. Pharmacotherapy includes the use of corticosteroids during acute HO flares and NSAIDs between flares; however, these agents do not mitigate disease progression. Palovarotene stimulates retinoid signaling, a regulator of skeletal formation, and in turn, inhibits chrondrogenesis. If approved, palovarotene will be the first DMT available to treat the underlying cause of FOP. In the pivotal trial, chronic use of palovarotene and episodic dose increases for HO flares led to a significant reduction in new HO formation. However, PPC or epiphyseal disorder was reported in skeletally immature patients treated with palovarotene.

Other oral agents in the pipeline (phase 2 trials) for FOP include IPN60130 (Ipsen) and INCB000928 (Incyte). In addition, Regeneron is expected to submit their injectable garetosmab to the FDA in 2024 or beyond, which demonstrated a reduction in the number of new (90%) and existing (25%) bone lesions in adults. While the phase 2 trial reported an increased mortality in patients treated with garetosmab, no causal link to the drug was found. A phase 3 trial is planned.

PROPOSED INDICATIONS

Candidemia and invasive candidiasis treatment

CLINICAL OVERVIEW

Rezafungin is an echinocandin antifungal.

The double-blind, phase 3 ReSTORE study evaluated the efficacy and safety of rezafungin in patients with candidemia and/or invasive candidiasis. A total of 199 patients were randomized 1:1 to treatment with rezafungin or caspofungin. Non-inferiority was demonstrated with rezafungin compared to caspofungin based on coprimary endpoints of global cure on day 14 (59.1% versus 60.6%, respectively) and all-cause mortality on day 30 (23.7% versus 21.3%, respectively). A negative blood culture was reported at 24 hours in 53.7% and 46.2% of patients in the rezafungin and caspofungin groups, respectively, and at 48 hours in 74.2% and 64.1% of patients, respectively. The median time to a negative blood culture was 23.9 and 27 hours, respectively. Serious TEAEs were reported in 2% of patients in the rezafungin group and 3.1% in the caspofungin group. In total, 13.3% and 11.2% of patients, respectively, discontinued therapy due to an adverse event.

Rezafungin was administered IV as a 400 mg loading dose in week 1, followed by 200 mg once weekly for a total of 2 to 4 doses. Caspofungin was administered IV as a 70 mg loading dose on day 1, followed by 50 mg IV once daily for up to 28 days; after ≥ 3 days of treatment, patients meeting certain study protocol criteria could be switched from caspofungin to oral fluconazole.

PLACE IN THERAPY

Invasive candidiasis is a serious infection. While candidemia is the most common form of invasive candidiasis, it can also affect the heart, brain, eyes, bones, or other organs. An estimated 25,000 cases of candidemia occur nationwide each year. Most invasive candidiasis infections arise from the usual Candida flora in/on the body that spreads after disruption of skin and mucosal barriers. A less common cause is contamination from Candida transmitted in a healthcare setting. Individuals at risk include those who are immunocompromised, organ transplant recipients, recent surgical recipients, in the ICU, on hemodialysis, and injectable drug users, and patients who have a central venous catheter or diabetes.

Once-daily IV echinocandin antifungals (caspofungin, anidulafungin, and micafungin) are the SOC for the initial treatment of candidemia and invasive candidiasis. Rezafungin is an echinocandin antifungal with a prolonged half-life that permits for once-weekly IV dosing. In clinical trials, it proved to be non-inferior based on clinical cure and all-cause mortality and demonstrated a similar safety profile compared to caspofungin (with optional step-down therapy to oral fluconazole). Rezafungin’s once-weekly dosing schedule could allow for outpatient or inpatient administration.

Rezafungin is also in phase 3 evaluation for the prevention of invasive fungal diseases in adults undergoing allogeneic blood and marrow transplantation. Ibrexafungerp (Brexafemme®), a triterpenoid antifungal, is also in phase 3 trials for candidemia and invasive candidiasis.

toripalimab IV

PROPOSED INDICATIONS

Advanced recurrent or metastatic nasopharyngeal cancer (NPC) as 1st-line treatment in combination with chemotherapy (gemcitabine and cisplatin) and as monotherapy for 2nd-line or later treatment in patients with disease progression on or after platinum-containing chemotherapy

CLINICAL OVERVIEW

Toripalimab is an anti-programmed death-1 (PD-1) monoclonal antibody.

A randomized, double-blind, placebo-controlled, phase 3 trial conducted in China, Singapore, and Taiwan evaluated the safety and efficacy of toripalimab 240 mg IV every 3 weeks as add-on therapy to gemcitabine and cisplatin for up to 6 treatment cycles as 1st-line treatment in 289 patients with advanced recurrent or metastatic NPC. The study revealed that the addition of toripalimab to gemcitabine/cisplatin significantly improved the primary endpoint of median PFS compared to chemotherapy alone (11.7 versus 8 months, respectively; p=0.0003). Improvement in secondary endpoints was also seen including ORR (77.4% versus 66.4%, respectively; p=0.0335) and median DOR (10 versus 5.7 months, respectively; p=0.0014). At a cutoff date of February 18, 2021, a 40% reduction in the risk of death was observed (HR, 0.603; p=0.0462) with the addition of toripalimab to chemotherapy compared to chemotherapy alone. Grade ≥ 3 adverse events occurred in 89% and 89.5% of patients in each group, respectively, and 7.5% and 4.9% of patients, respectively, discontinued therapy due to adverse events.

In the open-label, single-arm POLARIS-02 trial conducted in China, toripalimab 3 mg/kg was administered IV every 2 weeks to patients with NPC refractory to prior standard chemotherapy. The majority of patients had a non-keratinizing NPC histology subtype. One year after the first enrollment, a total of 190 patients were assessed. In this group, the primary endpoint of ORR was 20.5%. Secondary endpoint data revealed a DCR of 40%, median time to response of 1.8 months, median DOR of 12.8 months, median PFS of 1.9 months, and median OS of 17.4 months. In addition, toripalimab demonstrated benefit in patients who had received ≥ 2 prior lines of systemic therapy (ORR, 23.9%; DOR, 21.5 months; OS, 15.1 months). Among the 8 patients with keratinizing NPC, ORR was 62.5%.

PLACE IN THERAPY

NPC accounts for approximately 0.7% of all cancers worldwide. It is most prevalent in east and southeast Asia and is more common in men. NPC is associated with a high risk of metastases at distant sites. In low-risk areas, such as the US, new cases peak around the ages of 15 to 24 years and again at 64 to 79 years. The 5-year relative survival rate of NPC is 62% (all stages combined). Epstein-Barr virus (EBV) infection is closely associated with non-keratinizing NPC, which makes up the majority of global cases. Notably, EBV plasma levels have been used to measure residual disease and predict treatment outcomes.

Radiation therapy ± chemotherapy is the SOC for all stages of NPC. Gemcitabine/cisplatin is preferred as 1stline pharmacotherapy for recurrent or metastatic NPC in patients who are ineligible for surgery or radiation therapy. Other combinations recommended in this setting include a platinum agent plus 5-fluorouracil or the EGFR inhibitor cetuximab. To date, no PD-1/PD-L1 inhibitor has been approved to treat NPC, although the NCCN supports off-label use of pembrolizumab (Keytruda®) or nivolumab (Opdivo®) in combination with gemcitabine/cisplatin as 1st-line therapy for recurrent or metastatic disease. In small clinical trials, in PD-L1-positive patients, the ORR with pembrolizumab was 26% (partial responses only) and approximately 20.5% with nivolumab.

If approved, toripalimab will be the first checkpoint inhibitor indicated to treat NPC. Toripalimab combined with chemotherapy has the potential to become the new SOC for advanced recurrent or metastatic NPC. Toripalimab is also in phase 3 trials for esophageal cancer, HCC, NSCLC, and RCC.

Biosimilar Overview

CLINICAL OVERVIEW

Biosimilars are very different from generic drugs in that they are not exact duplicates of their reference biologic product. The FDA approval process for biosimilars is designed to ensure that the biosimilar product is highly similar to the reference product without having any meaningful clinical differences. Moreover, an interchangeable biological product is a biosimilar that is expected to produce the same clinical result as the reference product in any given patient. Switching or alternating between the reference and interchangeable products should have been evaluated and should not negatively impact the safety and efficacy of therapy.

Many controversies have surrounded biosimilars, and regulatory and litigation hurdles remain. The FDA has issued final and draft guidances. Select FDA biosimilar guidances are noted here. In January 2017, the agency issued final guidance on the nonproprietary naming of biologic products, which also applies to biosimilars. The biological products must bear a core name followed by a distinguishing 4-letter, lowercase, hyphenated suffix that is devoid of meaning. The international nonproprietary name (INN) impacts interchangeability as it affects pharmacists’ ability to substitute an interchangeable biosimilar for the reference product.

The FDA withdrew the September 2017 draft industry guidance on determining similarity of a proposed biosimilar product to its reference product to allow for further consideration of the most current and relevant scientific methods in evaluating analytical data. The agency focuses on providing flexibility for the efficient development of biosimilars while maintaining high scientific standards. In July 2018, the FDA finalized its guidance on labeling biosimilars. The guidance pertains to prescribing information (PI) but does not contain specific recommendations on interchangeability in the labeling. The labeling guidance provides recommendations on how to include, identify, and differentiate the biosimilar and the reference product in various sections of the PI. The basic premise remains that the originator product’s safety and effectiveness can be relied upon for HCPs to make prescribing decisions; therefore, a biosimilar should include relevant data from the originator in its PI. In May 2019, the agency released its final guidance on interchangeability. Most states have enacted biosimilar substitution laws. An interchangeable product may be substituted for the originator at the pharmacy without the involvement of the prescriber. The Purple Book is an FDA database of licensed biological products that lists biosimilar and interchangeable products. The FDA has approved 3 biosimilars for interchangeability to their reference product: insulin glargine-yfgn (Semglee®), adalimumabadbm (Cyltezo®), and ranibizumab-eqrn (Cimerli™).

Biosimilars can receive extrapolation to gain an indication without direct trials of the biosimilar for the eligible indication(s) of the reference products without requiring additional trials. Nevertheless, as each biosimilar comes to market, it will need to be considered individually. The FDA historically regulated insulins as small molecules. However, effective March 23, 2020, drugs such as insulin and growth hormone were deemed biologics and transitioned from the drug pathway to the biologic pathway. Their licensure as biologics allows these agents to be considered in the biosimilar space and promotes competition and access.

PLACE IN THERAPY

The patents of several biologic drugs are set to expire in the next few years, opening the US market for biosimilar entry; however, patent litigation has resulted in significant launch delays of FDA-approved biosimilars. In June 2017, the US Supreme Court issued 2 landmark rulings: (1) allowing a biosimilar manufacturer to provide launch notice of commercial marketing to the originator manufacturer before or after FDA approval of the biosimilar product and (2) eliminating any federal requirement for disclosure, also known as the “patent dance.” Some states, however, mandate disclosure. These decisions may bring biosimilars to the market sooner and potentially create price competition in the marketplace.

In July 2018, the FDA unveiled its Biosimilar Action Plan (BAP), a series of 11 steps to encourage biosimilar market competition, some of which were previously announced or underway. The BAP contains 4 key strategies: (1) improve the biosimilar development and approval process; (2) maximize scientific and regulatory clarity for sponsors; (3) provide effective communications for patients, clinicians, and payers; and (4) reduce unfair tactics that may delay market approval and entry. The BAP strives to promote access to biosimilar products and reduce healthcare costs.

To date, a

Zaxio® (filgrastim-sndz)

Inflectra® (infliximab-dyyb)

Erelzi® (etanercept-szzs)

Amjevita™* (adalimumab-atto)

Renflexis® (infliximab-abda)

Cyltezo* (adalimumab-adbm)

Mvasi® (bevacizumab-awwb)

Ixifi™ (infliximab-qbtx)†

Ogivri® (trastuzumab-dkst)

Novartis/Sandoz March 2015

Pfizer/Celltrion April 2016

Neupogen® (Amgen)

Remicade® (Janssen)

Novartis/Sandoz August 2016 Enbrel® (Amgen)

Amgen September 2016 Humira® (Abbvie)

Samsung Bioepis/ Merck May 2017

Boehringer Ingelheim August 2017

Amgen September 2017

Remicade (Janssen)

Humira (Abbvie)

Avastin® (Genentech)

Pfizer December 2017 Remicade (Janssen)

Viatris December 2017

Herceptin® (Genentech)

Retacrit® (epoetin alfa-epbx)

Nivestym® (filgrastim-aafi)

Hyrimoz™* (adalimumab-adaz)

Udenyca® (pegfilgrastim-cbqv)

Truxima® (rituximab-abbs)

Herzuma® (trastuzumab-pkrb)

Ontruzant® (trastuzumab-dttb)

Trazimera™ (trastuzumab-qyyp)

Eticovo™ (etanercept-ykro)

Kanjinti™ (trastuzumab-anns)

Zirabev® (bevacizumab-bvzr)

Hadlima™* (adalimumab-bwwd)

Ruxience® (rituximab-pvvr)

Abrilada™* (adalimumab-afzb)

Ziextenzo® (pegfilgrastim-bmez)

Pfizer/Hospira May 2018

Viatris June 2018

Epogen® (Amgen) Procrit® (Janssen) Fulphila® (pegfilgrastim-jmdb)

Neulasta® (Amgen)

Pfizer July 2018  Neupogen (Amgen)

Novartis/Sandoz October 2018 Humira (Abbvie)

Coherus November 2018

Celltrion/Teva November 2018

Celltrion/Teva December 2018

Samsung Bioepis/ Merck January 2019

Pfizer March 2019

Neulasta (Amgen)

Rituxan® (Genentech)

Herceptin (Genentech)

Herceptin (Genentech)

Herceptin (Genentech)

Samsung Bioepis/ Merck April 2019 Enbrel (Amgen)

Amgen June 2019

Pfizer June 2019

Samsung Bioepis/ Merck July 2019

Pfizer July 2019

Herceptin (Genentech)

Avastin (Genentech)

Humira (Abbvie)

Rituxan (Genentech)

Pfizer November 2019 Humira (Abbvie)

Novartis/Sandoz November 2019

Neulasta (Amgen)

BIOSIMILARS

Brand Name (Nonproprietary name) Manufacturer Approval Date Interchangeable Commercially Available Originator (Manufacturer)

APPROVED BIOSIMILARS

Avsola® (infliximab-axxq)

Nyvepria™ (pegfiltrastim-apgf)

Semglee (insulin glargine-yfgn)

Hulio®* (adalimumab-fkjp)

Riabni™ (rituximab-arrx)

Byooviz™ (ranibizumab-nuna)

Rezvoglar™ (insulin glargine-aglr)

Yusimry™* (adalimumab-aqvh)

Releuko® (filgrastim-ayow)

Alymsys® (bevacizumab-maly)

Fylnetra® (pegfilgrastim-pbbk)

Cimerli (ranibizumab-eqrn)

Stimufend® (pegfilgrastim-fpgk)

Vegzelma® (bevacizumab-adcd)

Amgen December 2019

Pfizer June 2020

Viatris July 2021

Remicade (Janssen)

Neulasta (Amgen)

Lantus® (Sanofi-Aventis)

Viatris July 2020 Humira (Abbvie)

Amgen December 2020

Biogen/Samsung Bioepis September 2021

Rituxan (Genentech)

Lucentis® (Genentech)

Eli Lilly December 2021 Lantus (Sanofi)

Coherus December 2021 Humira (Abbvie)

Amneal March 2022

Amneal April 2022

Amneal May 2022

Neupogen (Amgen)

Avastin (Genentech)

Neulasta (Amgen)

Coherus August 2022   Lucentis (Genentech)

Fresenius Kabi September 2022 Neulasta (Amgen)

Celltrion September 2022 Avastin (Genentech)

* Abbvie’s adalimumab (Humira) is available in 50 mg/mL (with citric acid/citrate) and 100 mg/mL (citrate-free) concentrations. All biosimilars for the product are approved as 50 mg/mL concentrations. Adalimumab-bwwd (Hadlima) by Samsung Bioepis/Merck is also approved as a 100 mg/mL high concentration citrate-free formulation (approved in August 2022).

† Pfizer already has Inflectra on the market and has not announced plans to launch Ixifi. Also available are Eli Lilly’s Basaglar® insulin glargine, a follow-on to Sanofi’s Lantus, and Sanofi’s Admelog® insulin lispro approved as a follow-on to Eli Lilly’s Humalog®

Specialty medications, which include biologics, continue to grow and constitute a large part of drug spend. In the US, it is estimated that biosimilars will cost approximately 15% to 35% less than the originator product, although price dynamics vary. Further, the potential cost savings can vary based on the market segment where brand contracts can play a role. A host of factors will contribute to market acceptability and the potential success of biosimilars. Payers, pharmacies, prescribers, and patients each play an important role in market adoption of biosimilars.

Brand Name (Nonproprietary name)

Approval Date Interchangeable Commercially Available Originator (Manufacturer)

BIOSIMILAR OVERVIEW continued IMMUNOLOGY adalimumab SC

Fresenius is seeking approval for its investigational biosimilar to Abbvie’s Humira 50 mg/mL; Celltrion and Sandoz are seeking approval for their investigational biosimilars to Abbvie’s citrate-free, high-concentration (100 mg/mL) Humira. Abbvie’s Humira is a tumor necrosis factor alpha (TNF-α) blocker indicated for the treatment of autoimmune disorders, including rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), plaque psoriasis (PSO), psoriatic arthritis (PsA), Crohn’s disease (CD) in adults and children, ulcerative colitis (UC), hidradenitis suppurativa (HS), and non-infectious uveitis.

Pfizer is seeking interchangeability of FDA-approved adalimumab-afzb (Abrilada) 50 mg/mL.

FDA APPROVAL TIMELINE

50 mg/mL

• Fresenius (MSB11022) – October to December 2022

• Pfizer (Abrilada) – October to December 2022 for interchangeability

100 mg/mL

• Celltrion (Yuflyma) – Pending

• Sandoz (Hyrimoz) – March to April 2023

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $18,552 $10,899 $7,231 $5,527 $4,423

The forecast is a projection of total US sales per year for the branded originator product

OPHTHALMOLOGY

aflibercept intravitreal

Viatris/Janssen

Viatris/Janssen is seeking approval of their investigational biosimilar (M710) to Regeneron’s Eylea ®, a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), and diabetic retinopathy (DR).

FDA APPROVAL TIMELINE

October 2022

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $6,221 $6,303 $6,009 $5,338 $4,618

The forecast is a projection of total US sales per year for the branded originator product

BIOSIMILAR OVERVIEW continued ONCOLOGY bevacizumab IV

Bio-Thera Solutions/Novartis, Centus, Samsung Bioepis/Organon, and Viatris/Biocon are seeking approval for their investigational biosimilars to Genentech’s Avastin, a vascular endothelial growth factor (VEGF)-specific angiogenesis inhibitor indicated for the treatment of metastatic colorectal cancer, nonsquamous non-small cell lung cancer, glioblastoma, metastatic renal cell carcinoma (RCC), and recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

FDA APPROVAL TIMELINE

• Bio-Thera Solutions/Novartis (BAT1706) – Pending

• Centus (FKB238) – Pending

• Samsung Bioepis/Organon (Aybintio) – Pending

• Viatris/Biocon (Bmab-100) – Pending

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $623 $487 $424 $381 $343

The forecast is a projection of total US sales per year for the branded originator product

BLOOD MODIFIER filgrastim IV, SC

Apotex and Tanvex are seeking approval of their investigational biosimilars to Amgen’s Neupogen, a leukocyte growth factor indicated for use in patients with nonmyeloid malignancies who are receiving myelosuppressive anti-cancer drugs; following induction or consolidation chemotherapy for acute myeloid leukemia (AML); with nonmyeloid malignancies in patients who are undergoing myeloablative chemotherapy followed by bone marrow transplantation; to mobilize autologous hematopoietic progenitor cells for collection by leukapheresis; with symptomatic congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia; and in patients who are acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome [HSARS]).

FDA APPROVAL TIMELINE

• Apotex – Pending

• Tanvex – February 2023

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $78 $66 $59 $52 $47

The forecast is a projection of total US sales per year for the branded originator product

BIOSIMILAR OVERVIEW continued

NEUROLOGY natalizumab IV

Polypharma Biologics/Novartis

Polypharma Biologics/Novartis is seeking approval for their investigational biosimilar to Biogen’s Tysabri®, an integrin receptor antagonist indicated for treatment of multiple sclerosis (MS) and Crohn's disease (CD).

FDA APPROVAL TIMELINE

May to June 2023

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $1,143 $1,108 $1,100 $1,108 $1,121

The forecast is a projection of total US sales per year for the branded originator product

BLOOD MODIFIER pegfilgrastim SC

Apotex and Lupin are seeking approval for their investigational biosimilars to Amgen’s Neulasta, a leukocyte growth factor indicated for use in patients with nonmyeloid malignancies who are receiving myelosuppressive anti-cancer drugs and in patients acutely exposed to myelosuppressive doses of radiation (HSARS).

FDA APPROVAL TIMELINE

• Apotex (Lapelga) – Pending

• Lupin (Lupifil-P) – Pending

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $957 $708 $620 $563 $528

The forecast is a projection of total US sales per year for the branded originator product

BIOSIMILAR OVERVIEW

IMMUNOLOGY

tocilizumab IV, SC

Fresenius/Merck

Fresenius/Merck is seeking approval for their investigational biosimilar to Genentech’s Actemra®, an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of rheumatoid arthritis (RA), giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular and systemic juvenile idiopathic arthritis (JIA), and cytokine release syndrome.

FDA APPROVAL TIMELINE

April to June 2023

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $1,763 $1,497 $1,194 $1,092 $884

The forecast is a projection of total US sales per year for the branded originator product.

ONCOLOGY trastuzumab IV

Novartis

Novartis is seeking approval for their investigational biosimilars to Genentech’s Herceptin, a HER2/neu receptor antagonist indicated for the treatment of HER2-overexpressing breast cancer and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma.

FDA APPROVAL TIMELINE

December 20, 2022

FINANCIAL FORECAST (reported in millions)

Year 2022 2023 2024 2025 2026

Projected Total US Sales $463 $386 $336 $298 $267

The forecast is a projection of total US sales per year for the branded originator product

Keep on Your RADAR

Notable

identified in this

significant clinical and financial

the MRx Pipeline radar. These

proposed indication, as well as an

are displayed. The financials are

zuranolone

datopotamab deruxtecan

moxeparvovec Musculoskeletal/

therapy

etrasimod

exagamglogene

gantenerumab

with

Pipeline DRUG

(CRL).

PIPELINE DRUG LIST

 Specialty drug names appear in magenta throughout the publication.

Submitted (New Drugs)

aflibercept (biosimilar to Regeneron’s Eylea)

Viatris/Janssen DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD

bulevirtide Gilead Hepatitis D infection treatment (in patients with compensated liver disease)

Intravitreal

Submitted − BLA October 2022

SC

Submitted − BLA; Breakthrough Therapy; Orphan Drug

Oct−Nov 2022

microbiota suspension Ferring

Clostridioides difficile infection (recurrent)

Rectal

Fresenius RA; AS; PSO; PsA; JIA; CD; UC SC

Submitted − BLA; Breakthrough Therapy; Fast Track; Orphan Drug

Submitted − BLA Oct−Dec 2022

Oct−Nov 2022 adalimumab 50 mg/mL (biosimilar to Abbvie’s Humira)

infliximab SC Celltrion IBS SC

cipaglucosidase alfa Amicus Pompe disease (in combination with oral miglustat)

Submitted − BLA; Orphan Drug; Priority Review Oct−Dec 2022

Submitted − BLA Oct−Dec 2022 tremelimumab AstraZeneca HCC (as single priming dose for durvalumab) IV

IV

teplizumab Provention Bio T1DM (delay/prevention) IV

etranacogene dezaparvovec

CSL Behring

Hemophilia B IV

Submitted − BLA; Breakthrough Therapy; Orphan Drug

Submitted − BLA; Breakthrough Therapy; Orphan Drug

Submitted − BLA; Breakthrough Therapy; Orphan Drug; Priority Review

poziotinib Spectrum NSCLC (HER2 exon 20 insertion mutations, locally advanced or metastatic, previously treated)

mirvetuximab soravtansine Immunogen

Ovarian cancer (folate receptor alpha (FRα)high platinum-resistant, 1−3 prior systemic treatments)

omburtamab Y-mAbs

Brain cancer (CNS/ leptomeningeal metastasis from neuroblastoma)

10/29/2022

11/17/2022

11/24/2022

Oral Submitted − NDA; Fast Track 11/24/2022

IV Submitted − BLA; seeking Accelerated Approval; Fast Track; Orphan Drug; Priority Review

Intracerebroventricular

Submitted − BLA; Breakthrough Therapy; Orphan Drug; Priority Review

11/28/2022

11/30/2022

terlipressin Mallinckrodt Hepatorenal syndrome

IV

Oral

Submitted − NDA; Fast Track; Orphan Drug December 2022 adagrasib Mirati NSCLC (KRAS G12C mutation, ≥ 1 prior systemic therapy)

Submitted − NDA; seeking Accelerated Approval; Breakthrough Therapy; RTOR

trastuzumab (biosimilar to Genentech’s Herceptin)

Novartis

Breast cancer; Gastric/ gastroesophageal cancer

IV

12/14/2022

Submitted − BLA 12/20/2022

NAME

toripalimab Coherus

Nasopharyngeal cancer (recurrent or metastatic, 1st-line in combination with chemotherapy, subsequent monotherapy)

IV

FORM

Submitted − BLA; Breakthrough Therapy; Orphan Drug

12/23/2022

lenacapavir Gilead HIV-1 infection (heavily treatment-experienced) Oral, SC Submitted − NDA; Breakthrough Therapy 12/27/2022 ublituximab TG MS (relapsing)

IV

IV

palovarotene Ipsen Fibrodysplasia ossificans progressiva (prevention of heteropopic ossification)

Oral

Submitted − BLA; Breakthrough Therapy; Orphan Drug; Priority Review

Submitted − NDA; Breakthrough Therapy; Fast Track; Orphan Drug; Priority Review; Rare Pediatric Disease

12/29/2022

Submitted − BLA 12/28/2022 mosunetuzumab Genentech Follicular lymphoma (R/R, ≥ 2 prior systemic therapies)

12/29/2022

treosulfan Medac Allogenic-HSCT conditioning IV Submitted − NDA; Orphan Drug January 2023

budesonide/albuterol AstraZeneca Asthma Inhaled Submitted − NDA Jan−Feb 2023 donanemab Eli Lilly Alzheimer’s disease (early) IV Submitted − BLA; seeking Accelerated Approval; Breakthrough Therapy; Priority Review

Jan−Feb 2023

pirtobrutinib Eli Lilly Mantle cell lymphoma Oral Submitted − NDA; Priority Review Jan−Feb 2023

zavegepant Biohaven/BristolMyers Squibb Migraine treatment Intranasal Submitted − NDA Jan−Mar 2023 dasatinib Xspray CML Oral

Submitted − 505(b)(2) NDA; Orphan Drug Jan−Jun 2023 velmanase alfa Chiesi Alpha-mannosidosis IV Submitted − NDA; Orphan Drug Jan−Jun 2023 pineapple proteolytic enzymes extract Vericel Burn injury Topical Submitted − BLA; Orphan Drug 01/01/2023 lecanemab Eisai/Biogen Alzheimer’s disease (early) IV Submitted − BLA; seeking Accelerated Approval; Breakthrough Therapy; Fast Track; Priority Review

01/06/2023

sodium phenylbutyrate oral suspension

Acer Urea cycle disorders Oral Submitted − 505(b)(2) NDA 01/15/2023 filgrastim (biosimilar to Amgen’s Neupogen) Tanvex Neutropenia/leukopenia IV, SC Submitted − BLA February 2023 daprodustat GlaxoSmithKline Anemia due to CKD (dialysis-dependent, dialysis-independent)

Topical

Submitted − BLA; Fast Track; Orphan Drug; Priority Review; Rare Pediatric Disease; RMAT

02/17/2023

Oral Submitted − NDA 02/01/2023 olutasidenib Forma AML Oral Submitted − NDA; Orphan Drug 02/15/2023 beremagene geperpavec Krystal Biotech Epidermolysis bullosa (dystrophic)

PIPELINE DRUG

NAME

elacestrant Menarini

Breast cancer (ER+/HER2-, advanced or metastatic)

sparsentan Travere/BristolMyers Squibb Immunoglobulin A nephropathy (Berger’s disease)

fezolinetant Astellas Menopause-associated vasomotor symptoms (VMS)

Oral

Oral

Submitted − NDA; Fast Track; Priority Review 02/17/2023

Submitted − NDA; seeking Accelerated Approval; Orphan Drug; Priority Review

02/17/2023

Oral

efanesoctocog alfa Sanofi Hemophilia A IV

Submitted − NDA; Priority Review 02/22/2023

Submitted − BLA; Breakthrough Therapy; Fast Track; Orphan Drug; Priority Review

02/28/2023

omaveloxolone Reata/Abbvie Friedreich’s ataxia Oral

Submitted − NDA; Fast Track; Orphan Drug; Priority Review; Rare Pediatric Disease

02/28/2023

omecamtiv mecarbil Cytokinetics Chronic heart failure (with reduced ejection fraction) Oral

Submitted − NDA; Fast Track 02/28/2023

naloxone Amphastar Opioid overdose Intranasal Submitted − 505(b)(2) NDA March 2023

remestemcel-L Mesoblast Limited GVHD (acute, steroidrefractory, in children) IV

trofinetide Acadia Rett syndrome (ages ≥ 2 years) Oral

Submitted − BLA; Fast Track; Orphan Drug; Priority Review

Submitted − NDA; Fast Track; Orphan Drug; Priority Review

Mar−May 2023

03/12/2023

rezafungin Cidara/Melinta Candidemia/invasive candidiasis IV

Submitted − NDA; Fast Track; Orphan Drug; Priority Review; QIDP

03/22/2023 leniolisib Pharming/Novartis Activated PI3K-delta syndrome Oral

Biomarin Hemophilia A IV

Submitted − NDA; Orphan Drug; Priority Review

Submitted − BLA; Breakthrough Therapy; Orphan Drug; RMAT

03/31/2023

03/29/2023 valoctocogene roxaparvovec

anthrax vaccine, adsorbed Emergent Anthrax infection (postexposure prophylaxis) IM

Fresenius/Merck RA; Polyarticular JIA; Systemic JIA IV, SC Submitted − BLA Apr−Jun 2023

Submitted − BLA; Fast Track April 2023 ritlecitinib Pfizer Alopecia areata (ages ≥ 12 years) Oral Submitted − NDA; Breakthrough Therapy Apr−Jun 2023 tocilizumab (biosimilar to Genentech’s Actemra)

tofersen Biogen ALS (superoxide dismutase 1) Intrathecal

Submitted − NDA; Orphan Drug; Priority Review

04/25/2023

mirikizumab Eli Lilly UC IV, SC Submitted − BLA 04/28/2023 sotagliflozin Lexicon Heart failure (with or without diabetes) Oral Submitted − NDA May 2023 natalizumab (biosimilar to Biogen’s Tysabri)

Polypharma Biologics/Novartis

CD; MS IV Submitted − BLA May−Jun 2023

NAME

(vic-)trastuzumab duocarmazine

Byondis

Breast cancer (HER2+, unresectable locally advanced or metastatic)

IV

Submitted − BLA; Fast Track 05/12/2023

foscarbidopa/foslevodopa Abbvie

Parkinson’s disease motor fluctuations SC

Submitted − NDA 05/20/2023 nogapendekin alfa inbakicept

Immunitybio Bladder cancer (BCG-unresponsive, non-muscle invasive carcinoma in situ, in combination with BCG)

Intravesical

Submitted − BLA; Breakthrough Therapy; Fast Track

05/23/2023 sotagliflozin Lexicon Heart failure in patients with T2DM Oral Submitted − NDA 05/31/2023

carbidopa/levodopa IR/ER Amneal

Parkinson’s disease Oral Submitted − 505(b)(2) NDA June 2023 aripiprazole 2-month H. Lundbeck Bipolar disorder; Schizophrenia IM Submitted − 505(b)(2) NDA Jun−Jul 2023

landiolol Eagle Supraventricular tachycardia (short-term reduction of ventricular rate)

IV

Submitted − NDA 06/01/2023

momelotinib Sierra Oncology/ Gilead

Ophthalmic Submitted − NDA 06/28/2023

Myelofibrosis Oral Submitted − NDA; Fast Track; Orphan Drug 06/16/2023 perfluorohexyloctane Bausch + Lomb DED associated with Meibomian gland dysfunction

nirmatrelvir/ritonavir (Paxlovid™)

Pfizer COVID-19 treatment (high-risk patients) Oral

Submitted − NDA 06/30/2023 delandistrogene moxeparvovec

Sarepta/Genentech DMD IV

Submitted − BLA; seeking Accelerated Approval; Fast Track; Orphan Drug; Rare Pediatric Disease

Jul−Sep 2023 epinephrine ARS

Intranasal Submitted − 505(b)(2) NDA; Fast Track Jul−Sep 2023 firmacute eubacterial spores Seres

difficile-associated diarrhea prevention Oral Submitted − BLA; Breakthrough Therapy; Orphan Drug

SC Submitted − NDA; Orphan Drug Jul−Sep 2023

Jul−Sep 2023 motixafortide Biolinerx Stem cell mobilization for autologous BMT for muliple myeloma

Novaliq

Submitted − NDA Jul−Sep 2023

Submitted − 505(b)(2) NDA 08/09/2023

Intravitreal Submitted − BLA 08/30/2023 palopegteriparatide

Submitted − NDA; Orphan Drug 08/31/2023 efgartigimod/ hyaluronidase

Submitted − BLA; Orphan Drug September 2023 lotilaner Tarsus

Argenx

Submitted − NDA 09/07/2023 brimonidine tartrate 0.35%

blepharitis

Research

Celltrion RA; AS; PSO; PsA; JIA; CD;

Submitted − BLA Pending

Submitted − 505(b)(2) NDA 10/06/2023 adalimumab 100 mg/mL (biosimilar to Abbvie’s Humira)

bevacizumab (biosimilar to Genentech’s Avastin)

bevacizumab (biosimilar to Genentech’s Avastin)

Bio-Thera Solutions/ Novartis

Centus

Brain cancer; Cervical cancer; CRC; NSCLC; Ovarian cancer; RCC

Brain cancer; Cervical cancer; CRC; NSCLC; Ovarian cancer; RCC

IV

IV

Submitted − BLA Pending

Submitted − BLA Pending

bevacizumab (biosimilar to Genentech’s Avastin)

Samsung Bioepis/ Organon

Brain cancer; Cervical cancer; CRC; NSCLC; Ovarian cancer; RCC

Viatris/Biocon Brain cancer; Cervical cancer; CRC; NSCLC; Ovarian cancer; RCC

IV

IV Submitted − BLA Pending

Submitted − BLA Pending bevacizumab (biosimilar to Genentech’s Avastin)

casirivimab/imdevimab Regeneron COVID-19 treatment (outpatient setting) IM, IV, SC Submitted − BLA; Priority Review Pending filgrastim (biosimilar to Amgen’s Neupogen)

Apotex

Neutropenia/leukopenia SC

Submitted − BLA Pending

Neutropenia/leukopenia IV, SC Submitted − BLA Pending pegfilgrastim (biosimilar to Amgen’s Neulasta) Apotex Neutropenia/leukopenia SC Submitted − BLA Pending pegfilgrastim (biosimilar to Amgen’s Neulasta) Lupin

sabizabulin Veru COVID-19 treatment Oral Submitted − EUA; Fast Track Pending tislelizumab Beigene/Novartis Esophageal squamous cell carcinoma (unresectable or metastatic, 2nd-line)

tixagevimab/cilgavimab (Evusheld™)

IV Submitted − BLA; Orphan Drug Pending

AstraZeneca COVID-19 treatment IM, IV Submitted − BLA Pending

Submitted (Supplementals)

adalimumab-afzb 50 mg/mL (Abrilada) (biosimilar to Abbvie’s Humira)

Pfizer RA, PsA, JIA, AS, CD, UC, PSO, SC

COVID-19 treatment (hospitalized adults on systemic corticosteroids and require assisted ventilation)

IV

Submitted − PAS BLA for biosimilar interchangability

Oct−Dec 2022 tocilizumab (Actemra) Genentech

Submitted − sBLA; Priority Review Oct−Dec 2022

upadacitinib (Rinvoq™) Abbvie

Axial spondyloarthritis (non-radiographic)

Oral

Submitted − sNDA 11/07/2022

pegcetacoplan (Empaveli®) Apellis

Geographic atrophy (secondary to AMD)

Intravitreal

Submitted − sNDA; Fast Track; Priority Review 11/26/2022 ibrexafungerp (Brexafemme)

Scynexis

Recurrent vulvovaginal candidiasis prevention

Oral Submitted − sNDA; Fast Track; Orphan Drug; Priority Review; QIDP

11/30/2022 asparaginase erwina chysanthemi (recombinant)-rywn (Rylaze™ IM)

Jazz AML and Lymphblastic lymphoma (3 times a week IM dosing, with chemotherapy, ages ≥ 1 month, E. coli derived asparaginase hypersensitivity)

MDD (adjunct) Oral Submitted − sNDA 12/22/2022

IM Submitted − sBLA; Fast Track; Orphan Drug; RTOR 12/02/2022 cariprazine (Vraylar®) Abbvie

NAME MANUFACTURER CLINICAL USE

FORM DEVELOPMENT STATUS FDA DECISION

PIPELINE

abaloparatide (Tymlos®) Radius

Osteoporosis (men, highrisk for fracture)

SC Submitted − sNDA 12/23/2022

ibrutinib (Imbruvica®) Abbvie/Janssen GVHD treatment (ages ≥ 1 years, ≥ 2nd-line)

Oral

Submitted − sNDA; Breakthrough Therapy; Orphan Drug

12/28/2022 lanadelumab-flyo (Takhzyro®)

Takeda

HAE (prophylaxis of attacks) SC

Submitted − sBLA; Breakthrough Therapy; Fast Track; Orphan Drug

Jan−Jun 2023 daxibotulinumtoxin A (Daxxify™)

Submitted − sBLA; Orphan Drug Jan−Dec 2023 vonoprazan fumarate (Takecab®)

Revance Cervical dystonia IM

Phathom Erosive esophagitis; Heartburn relief Oral

Colorectal cancer (unresectable or metastatic, HER2+, prior chemotherapy, in combination with trastuzumab)

zanubrutinib (Brukinsa®) BeiGene CLL/SLL

pembrolizumab (Keytruda) Merck NSCLC (post surgical resection; stage 1B, II, or IIIA)

relugolix/estradiol/ norethindrone (Myfembree®)

asparaginase erwina chysanthemi (recombinant)-rywn (Rylaze IV)

sacituzumab govitecanhziy (Trodelvy®)

Myovant Uterine fibroids (premenopausal women)

Oral Submitted − sNDA; seeking Accelerated Approval; Breakthrough Therapy; Orphan Drug; Priority Review

01/19/2023

Submitted − sNDA 01/11/2023 tucatinib (Tukysa®) Seagen/Merck

Oral Submitted − sNDA; Orphan Drug 01/20/2023

IV

Oral

Jazz ALL IV

Submitted − sBLA 01/29/2023

Submitted − sNDA 01/29/2023

Submitted − sBLA; Fast Track; Orphan Drug; RTOR February 2023

Gilead Breast cancer (unresectable, locally advenced or metastatic, HR+/HER2-, post endocrine therapy and ≥ 2 additional lines of systemic metastic therapy)

aflibercept (Eylea) Regeneron Retinopathy of prematurity in preterm infants

aflibercept (Eylea) Regeneron Diabetic retinopathy (16-week maintenance regimen)

amifampridine phosphate (Firdapse®) Catalyst Lambert-Eaton myasthenic syndrome (pediatric)

adalimumab-adaz 100 mg/mL (Hyrimoz) (biosimilar to Abbvie’s Humira)

IV

Submitted − sBLA; Breakthrough Therapy; Fast Track; Orphan Drug

February 2023

Intravitreal

Intravitreal

Oral

Sandoz RA; AS; PSO; PsA; JIA; CD; UC SC

Submitted − sBLA; Orphan Drug; Priority Review

02/11/2023

Submitted − sBLA 02/28/2023

Submitted − sNDA; Breakthrough Therapy; Orphan Drug

March 2023

Submitted − sBLA Mar–Apr 2023

atogepant (Qulipta™) Abbvie Migraine prevention

Submitted − sNDA 05/26/2023

Submitted − sNDA 04/21/2023 durvalumab (Imfinzi®) AstraZeneca HCC (unresectable) IV Submitted − sBLA; Orphan Drug 04/30/2023 upadacitinib (Rinvoq) Abbvie CD (moderate to severe)

rucaparib (Rubraca®) Clovis

Ovarian cancer (1st-line, post 1st-line platinum chemotherapy)

Oral Submitted − sNDA; Breakthrough Therapy; Orphan Drug

07/12/2023

baricitinib (Olumiant®) Eli Lilly

Atopic dermatitis (moderate-severe)

Oral Submitted − sNDA Pending norgestrel (Opill®) Perrigo Contraception

AAV8-ranibizumab Regenxbio

Oral Submitted – Rx-to-OTC Pending Phase 3 (New Drugs)

AMD

Subretinal Phase 3 – BLA; Orphan Drug TBD

IV, SC Phase 3 – BLA; Fast Track TBD abiraterone acetate Tavanta Prostate cancer

abelacimab Anthos VTE

Oral Phase 3 – NDA TBD acoramidis Bridgebio/ AstraZeneca Transthyretin amyloid cardiomyopathy (ATTRCM)

Oral Phase 3 – NDA TBD

adintrevimab Adagio COVID-19

Alvotech DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD

aflibercept (biosimilar to Regeneron’s Eylea) Amgen DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD

aflibercept (biosimilar to Regeneron’s Eylea)

aflibercept (biosimilar to Regeneron’s Eylea)

Sam Chun Dang DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD

Samsung Bioepis/ Biogen DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD

aflibercept (biosimilar to Regeneron’s Eylea)

Santo/Formycon DME; Diabetic retinopathy; Macular edema following RVO; Wet AMD

Intravitreal Phase 3 – BLA TBD

IM Phase 3 – BLA TBD aflibercept (biosimilar to Regeneron’s Eylea)

Intravitreal Phase 3 – BLA TBD

Intravitreal Phase 3 – BLA TBD

Intravitreal Phase 3 – BLA TBD

Intravitreal Phase 3 – BLA TBD

aloradine Vistagen

anti-betv1 monoclonal

(REGN-57135714-5715)

Regeneron

asundexian

ataluren PTC

Phase 3 – BLA TBD

Intranasal Phase 3 – NDA; Fast Track TBD amubarvimab + romlusevimab Brii COVID-19

Phase 3 – BLA TBD

Phase 3 – BLA TBD

Phase 3 – NDA TBD

Phase 3 – NDA; Breakthrough Therapy; Fast Track; Orphan Drug; Rare Pediatric Disease

Phase 3 – NDA TBD

Phase 3 – NDA; Fast Track; Orphan Drug TBD

PIPELINE

autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells

autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors

Brainstorm ALS

Phase 3 – BLA; Fast Track; Orphan Drug; RMAT TBD

Intrathecal Phase 3 – BLA; Fast Track; Orphan Drug TBD

avacincaptad pegol Iveric Bio Dry AMD Intravitreal Phase 3 – NDA; Fast Track TBD avasopasem manganese Galera Mucositis IV Phase 3 – NDA; Breakthrough Therapy; Fast Track

TBD bamlanivimab Eli Lilly COVID-19 IV Phase 3 – BLA TBD batiraxcept Aravive Ovarian cancer IV Phase 3 – BLA; Fast Track TBD bentracimab Phasebio/ AstraZeneca Ticagrelor (Brilinta®) reversal IV Phase 3 – BLA; Breakthrough Therapy TBD beroctocog alfa Green Cross Hemophilia A IV Phase 3 – BLA TBD bimekizumab UCB Axial spondyloarthritis; Hidradenitis suppurativa; PsA

SC Phase 3 – BLA TBD

bis-choline tetrathiomolybdate

Janssen Retinitis pigmentosa Subretinal Phase 3 – BLA; Fast Track; Orphan Drug TBD

AstraZeneca Wilson’s disease Oral Phase 3 – NDA; Fast Track; Orphan Drug TBD botaretigene sparoparvovec

BPR277 Lifemax/Novartis Congenital ichthyosis Topical Phase 3 – NDA; Fast Track; Orphan Drug TBD brensocatib Insmed/AstraZeneca Bronchiectasis Oral Phase 3 – NDA; Breakthrough Therapy TBD buntanetap Annovis Parkinson’s disease Oral Phase 3 – NDA TBD cannabidiol gel Zynerba Fragile X syndrome Topical Phase 3 – NDA; Fast Track; Orphan Drug TBD capsaicin Centrexion Osteoarthritis pain (knee) Intraarticular Phase 3 – NDA; Fast Track TBD ceftobiprole medocaril Basilea

ABSSSI; Bacteremia; CAP; HAP IV Phase 3 – NDA; Fast Track; QIDP TBD ceftriaxone wearable micropump scPharmaceuticals Gram+/Gram- infection SC Phase 3 – NDA TBD clobetasol propionate Formosa Ocular pain and/or inflammation Ophthalmic Phase 3 – 505(b)(2) NDA TBD

CM-AT (pancreatic enzyme) Curemark Autism spectrum disorders Oral Phase 3 – BLA; Fast Track TBD cobitolimod Index/Merck UC Rectal Phase 3 – NDA; Orphan Drug TBD

concizumab Novo Nordisk Hemophilia A and B SC

Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

TBD copper histidine Zydus Cadila Menkes disease SC Phase 3 – NDA; Breakthrough Therapy; Fast Track; Orphan Drug

TBD cosibelimab Fortress Cutaneous squamous cell carcinoma (metastatic) IV Phase 3 – BLA TBD

CRISPR Therapeutics SCD; Thalassemia IV

PIPELINE

COVID-19 vaccine (C19VAZ; formerly AZD1222; ChAdOx1)

COVID-19 vaccine (JNJ78436735; formerly Ad26. COV2-S)

AstraZeneca COVID-19

Janssen

COVID-19

IM Phase 3 – BLA TBD

IM Phase 3 – BLA TBD

COVID-19 vaccine (MT2766) Medicago COVID-19 IM, SC Phase 3 – BLA; Fast Track TBD

COVID-19 vaccine (SCB2019) Clover COVID-19 SC Phase 3 – BLA TBD

COVID-19 vaccine (SP0253) Sanofi/ GlaxoSmithKline

COVID-19 IM Phase 3 – BLA TBD

COVID-19 vaccine, adjuvanted (Nuvaxovid™) Novavax COVID-19 IM Phase 3 – BLA TBD crovalimab Genentech Hemolytic uremic syndrome; PNH IV, SC Phase 3 – BLA; Orphan Drug TBD

cyclobenzaprine Tonix Fibromyalgia SL Phase 3 – 505(b)(2) NDA TBD dabocemagene autoficel Castle Creek Epidermolysis bullosa Intradermal Phase 3 – BLA; Fast Track; Orphan Drug; RMAT TBD danicopan AstraZeneca PNH Oral Phase 3 – NDA; Breakthrough Therapy; Orphan Drug

TBD darvadstrocel Takeda CD IV Phase 3 – BLA; Orphan Drug TBD

delgocitinib Leo Atopic dermatitis Topical Phase 3 – NDA; Fast Track TBD dengue tetravalent vaccine Takeda Dengue fever SC Phase 3 – BLA; Fast Track TBD denosumab (Biosimilar to Amgen’s Prolia®) Biocon Osteoporosis/osteopenia SC Phase 3 – BLA TBD denosumab (Biosimilar to Amgen’s Prolia) Celltrion

Osteoporosis/osteopenia SC Phase 3 – BLA TBD denosumab (Biosimilar to Amgen’s Prolia)

Fresenius

Osteoporosis/osteopenia SC Phase 3 – BLA TBD denosumab (Biosimilar to Amgen’s Prolia)

Gedeon Richter

Osteoporosis/osteopenia SC Phase 3 – BLA TBD denosumab (Biosimilar to Amgen’s Prolia)

Novartis

Osteoporosis/osteopenia SC Phase 3 – BLA TBD

Osteoporosis/osteopenia SC Phase 3 – BLA TBD denosumab (Biosimilar to Amgen’s Prolia) Teva

difluprednate XR Sun Ocular pain/inflammation Ophthalmic Phase 3 – NDA TBD donaperminogene seltoplasmid

Helixmith Diabetic foot ulcers (chronic non-healing) IM Phase 3 – BLA TBD doravirine/islatravir Merck HIV-1 infection treatment Oral Phase 3 – NDA TBD dovitinib lactate Allarity Breast cancer Oral Phase 3 – NDA TBD durlobactam/sulbactam Entasis Acinetobacter baumannii infection IV Phase 3 – NDA; Fast Track; QIDP TBD dust mite immunotherapy Stallergenes Greer Allergic rhinitis SL Phase 3 – BLA TBD EB-101 (gene therapy) Abeona Epidermolysis bullosa Surgical application Phase 3 – BLA; Breakthrough Therapy; Orphan Drug; RMAT

TBD ebselen Sound Meniere’s disease Oral Phase 3 – NDA; Fast Track TBD eculizumab (biosimilar to Alexion’s Soliris®)

Amgen PNH IV Phase 3 – BLA; Orphan Drug TBD

PIPELINE

efgartigimod/ hyaluronidase

Argenx

Bullous pemphigoid; ITP; Pemphigus vulgaris SC Phase 3 – sBLA; Orphan Drug TBD

elamipretide Stealth Barth syndrome SC Phase 3 – NDA; Fast Track; Orphan Drug TBD enmetazobactam Allecra UTI (complicated) IV Phase 3 – NDA; Fast Track; QIDP TBD

ensifentrine Verona COPD

SC Phase 3 – NDA; Orphan Drug TBD

Inhaled Phase 3 – NDA TBD ensovibep Novartis COVID-19 IV Phase 3 – BLA; Fast Track TBD epcoritamab Genmab DLBCL SC Phase 3 – BLA TBD epinephrine Bryn Anaphylaxis Intranasal Phase 3 – NDA; Fast Track TBD eplontersen Ionis/AstraZeneca Transthyretin amyloid cardiomyopathy; Transthyretin amyloid polyneuropathy

esreboxetine Axsome/Pfizer Fibromyalgia Oral Phase 3 – NDA TBD etanercept (biosimilar to Amgen’s Enbrel)

Coherus RA; Polyarticular JIA; AS; PSO; PsA SC Phase 3 – BLA TBD etavopivat Forma SCD Oral Phase 3 – NDA; Fast Track; Orphan Drug TBD

etesevimab Lonza/Eli Lilly COVID-19 IV Phase 3 – BLA TBD etrasimod Arena UC Oral Phase 3 – NDA; Orphan Drug TBD

evobrutinib Merck MS Oral Phase 3 – NDA TBD exagamglogene autotemcel Vertex SCD; Thalassemia IV Phase 3 – BLA; Fast Track; Orphan Drug; RMAT TBD fasinumab Regeneron Osteoarthritis pain (knee) SC Phase 3 – BLA TBD fexapotide triflutate Nymox BPH Intraprostatic Phase 3 – NDA TBD fidanacogene elaparvovec Pfizer/Genentech Hemophilia B IV Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

TBD filgotinib Gilead CD; UC Oral Phase 3 – NDA TBD firibastat Quantum Genomics Hypertension (systemic) Oral Phase 3 – NDA TBD fitusiran Sanofi Hemophilia A and B SC Phase 3 – NDA; Fast Track; Orphan Drug TBD follitropin alfa (biosimilar to EMD Serono’s Gonal-F®)

Allergan Female reproductive disorder SC Phase 3 – BLA TBD follitropin alfa (biosimilar to EMD Serono’s Gonal-F)

Finox Female reproductive disorder SC Phase 3 – BLA TBD FVIII mimetic bi-specific antibody Novo Nordisk Hemophilia A

Phase 3 – BLA; Orphan Drug TBD gantenerumab Genentech Alzheimer’s disease (early)

Phase 3 – BLA; Breakthrough Therapy TBD garadacimab CSL HAE

Phase 3 – BLA; Orphan Drug TBD gavorestat Applied Therapeutics Galactosemia

TBD GBT601 Global Blood Therapeutics SCD

Phase 3 – NDA; Fast Track; Orphan Drug; Rare Pediatric Disease

Phase 3 – NDA TBD gepotidacin GlaxoSmithKline UTI (uncomplicated)

Phase 3 – NDA; QIDP TBD giredestrant Genentech Breast cancer

Phase 3 – NDA; Fast Track TBD

giroctocogene fitelparvovec

Pfizer Hemophilia A

IV Phase 3 – BLA; Fast Track; Orphan Drug; RMAT TBD glatiramer acetate depot Viatris MS

IM Phase 3 – 505(b)(2) NDA TBD glofitamab Genentech DLBCL

IV Phase 3 – BLA TBD gold nanocrystal Clene ALS Oral Phase 3 – NDA; Orphan Drug TBD

human pentraxin-2 protein Genentech Idiopathic pulmonary fibrosis

hypericin Soligenix Cutaneous T-cell lymphoma (CTCL)

IV Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

TBD

Topical Phase 3 – NDA; Fast Track; Orphan Drug TBD

inavolisib Genentech Breast cancer

insulin aspart (biosimilar to Novo Nordisk’s Novolog®)

insulin glargine (biosimilar to Sanofi’s Lantus)

insulin icodec (once weekly)

IV Phase 3 – BLA; Orphan Drug TBD

Oral Phase 3 – NDA TBD inclacumab Global Blood Therapeutics SCD

Sanofi T1DM; T2DM SC Phase 3 – BLA TBD

Gan & Lee T1DM; T2DM SC Phase 3 – BLA TBD

Novo Nordisk T2DM SC Phase 3 – BLA TBD

Oral Phase 3 – NDA; Breakthrough Therapy; Orphan Drug; Rare Pediatric Disease

TBD

ipatasertib Genentech Prostate cancer Oral Phase 3 – NDA TBD iptacopan Novartis Complement 3 (C3) glomerulopathy; Hemolytic uremic syndrome; Immunoglobulin A nephropathy (Berger’s disease); PNH

itepekimab Regeneron/Sanofi COPD SC Phase 3 – BLA TBD Lactobacillus reuteri Infant Bacterial Therapeutics Necrotizing enterocolitis Oral Phase 3 – BLA; Orphan Drug TBD lanifibranor Inventiva NASH Oral Phase 3 – NDA; Breakthrough Therapy; Fast Track

TBD

lazertinib Genosco NSCLC Oral Phase 3 – NDA TBD lebrikizumab Eli Lilly Atopic dermatitis (moderate-severe) SC Phase 3 – BLA; Fast Track TBD

lenadogene nolparvovec Gensight Leber’s hereditary optic neuropathy Intravitreal Phase 3 – BLA; Orphan Drug TBD lenzilumab Humanigen COVID-19 IV Phase 3 – BLA TBD leriglitazone Minoryx Adrenoleukodystrophy Oral Phase 3 – NDA; Fast Track; Orphan Drug; Rare Pediatric Disease

TBD

leukocyte interleukin CEL-SCI SCCHN SC Phase 3 – BLA; Orphan Drug TBD levodopa/carbidopa patch pump Mitsubishi Tanabe Parkinson’s disease SC Phase 3 – 505(b)(2) NDA TBD

ligelizumab Novartis Urticaria SC Phase 3 – BLA; Breakthrough Therapy TBD linrodostat Bristol-Myers Squibb Bladder cancer Oral Phase 3 – NDA TBD litifilimab Biogen SLE SC Phase 3 – BLA TBD

PIPELINE

magrolimab Gilead

Myelodysplastic syndrome

IV Phase 3 – BLA; Breakthrough Therapy; Fast Track; Orphan Drug

TBD

Hemophilia A and B IV, SC Phase 3 – BLA; Fast Track; Orphan Drug TBD masitinib AB Science

marstacimab Pfizer

ALS; Alzheimer’s disease; Asthma (eosinophilic); Mastocytosis; MS

mavorixafor X4 Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome

melphalan Delcath Uveal melanoma (hepatic-dominant)

Oral Phase 3 – NDA; Orphan Drug TBD

Oral Phase 3 – NDA; Breakthrough Therapy; Fast Track; Orphan Drug; Rare Pediatric Disease

Percutaneous hepatic perfusion

TBD

Phase 3 – NDA TBD

meningococcal vaccine GlaxoSmithKline Meningococcal immunization

metachromatic leukodystrophy gene therapy

Orchard Metachromatic leukodystrophy

IM Phase 3 – BLA TBD

IM Phase 3 – BLA TBD meningococcal vaccine Pfizer Meningococcal immunization

IV Phase 3 – BLA; Orphan Drug; RMAT TBD

midomafetamine Multidisciplinary Association for Psychedelic Studies

PTSD

Oral Phase 3 – NDA; Breakthrough Therapy TBD minocycline Journey Rosacea

IV Phase 3 – NDA; Fast Track; QIDP TBD

Oral Phase 3 – 505(b)(2) NDA TBD minocycline/edetate/ethyl alcohol Citius Catheter-related bloodstream infection (CRBSI)

mirikizumab Eli Lilly CD

IV, SC Phase 3 – BLA TBD mitapivat Agios SCD; Thalassemia Oral Phase 3 – NDA; Orphan Drug TBD molnupiravir Merck COVID-19 Oral Phase 3 – NDA TBD nabiximols Jazz MS-related spasticity Oral transmucosal Phase 3 – NDA TBD nalbuphine ER Trevi Pruritus Oral Phase 3 – NDA; Fast Track TBD naloxone Orexo Opioid overdose Intranasal Phase 3 – 505(b)(2) NDA TBD naloxone hydrochloride dihydrate lotion Elorac Pruritus

Topical Phase 3 – NDA; Fast Track; Orphan Drug TBD narsoplimab Omeros Hemolytic uremic syndrome IV, SC Phase 3 – BLA; Fast Track TBD navitoclax Abbvie/Genentech Myelofibrosis Oral Phase 3 – NDA; Orphan Drug TBD

nedosiran Novo Nordisk Hyperoxaluria

SC Phase 3 – NDA; Breakthrough Therapy; Orphan Drug; Rare Pediatric Disease

TBD

nemolizumab Galderma Atopic dermatitis (moderate-severe); Pruritus

IV Phase 3 – BLA; Fast Track; Orphan Drug TBD

SC Phase 3 – BLA; Breakthrough Therapy TBD nipocalimab Janssen Autoimmune hemolytic anemia

PIPELINE

nirmatrelvir/ritonavir (Paxlovid)

Pfizer

COVID-19 post-exposure prophylaxis

Oral Phase 3 – sNDA TBD

nirogacestat Springworks Progressing desmoid tumors/aggressive fibromatosis

Oral Phase 3 – NDA; Breakthrough Therapy; Fast Track; Orphan Drug

TBD

TBD nirsevimab AstraZeneca RSV prevention IM Phase 3 – BLA; Breakthrough Therapy; Fast Track

nomacopan Akari

Bullous pemphigoid; Hemolytic uremic syndrome; HSCTassociated thrombotic microangiopathy; PNH

SC Phase 3 – BLA; Fast Track; Orphan Drug TBD

obefazimod Abivax UC

Oral Phase 3 – NDA TBD olezarsen Akcea Familial chylomicronemia syndrome SC Phase 3 – NDA TBD

OPT-302 Opthea Wet AMD Intravitreal Phase 3 – BLA; Fast Track TBD OTL-103 Orchar Wiskott-Aldrich syndrome IV Phase 3 – BLA; Orphan Drug; RMAT TBD

Oxalobacter formigenes Oxthera Hyperoxaluria Oral Phase 3 – BLA; Orphan Drug; Rare Pediatric Disease

TBD

padeliporfin Steba Bladder cancer IV Phase 3 – NDA; Fast Track; Orphan Drug TBD pamrevlumab Fibrogen COVID-19; DMD; Idiopathic pulmonary fibrosis; Pancreatic cancer

IV Phase 3 – BLA; Fast Track; Orphan Drug; Rare Pediatric Disease

TBD pegadricase Swedish Orphan Biovitrum Gout IV Phase 3 – BLA TBD pegzilarginase Aeglea Arginase 1 deficiency IV Phase 3 – BLA; Breakthrough Therapy; Fast Track; Orphan Drug; Rare Pediatric Disease

TBD phentolamine mesylate Ocuphire Dim light vision disturbances; Reverse pharmacologicallyinduced mydriasis

Ophthalmic Phase 3 – NDA TBD PL-9643 Palatin DED

IV Phase 3 – NDA; Breakthrough Therapy TBD

Ophthalmic Phase 3 – NDA TBD plinabulin Beyondspring Chemotherapy-induced neutropenia prevention; NSCLC

plonmarlimab I-Mab COVID-19 IV Phase 3 – BLA TBD pollinex quattro grass Allergy Therapeutics Allergic rhinitis SC Phase 3 – BLA TBD pollinex quattro ragweed Allergy Therapeutics Allergic rhinitis SC Phase 3 – BLA TBD potassium citrate/ potassium bicarbonate Advicenne Renal tubular acidosis Oral Phase 3 – 505(b)(2) NDA TBD pozelimab Regeneron Chaple disease; PHN IV, SC Phase 3 – BLA; Orphan Drug TBD

pritelivir Aicuris Anti-infective Cures Herpes simplex virus treatment Oral Phase 3 – NDA; Breakthrough Therapy; Fast Track

TBD prothrombin complex Octapharma Hemostasis

IV Phase 3 – BLA TBD proxalutamide Kintor COVID-19 Oral Phase 3 – NDA TBD

PIPELINE

ralinepag United Therapeutics PAH

ranibizumab (biosimilar to Genentech’s Lucentis)

Stada Arzneimittel/ Bausch

Wet AMD; Macular edema following RVO; Myopic choroidal neovascularization (mCNV)

Oral Phase 3 – NDA; Orphan Drug TBD

Intravitreal Phase 3 – BLA TBD

rapamycin Timber Tuberous sclerosis complex-associated facial angiofibromas

Topical Phase 3 – NDA TBD rapamycin (high-strength) Palvella Pachyonychia congenita Topical Phase 3 – NDA; Fast Track; Orphan Drug TBD

REGN1908-1909 Regeneron Allergic rhinitis SC Phase 3 – BLA TBD relacorilant Corcept Cushing’s syndrome Oral Phase 3 – NDA; Orphan Drug TBD

remibrutinib Novartis Urticaria Oral Phase 3 – NDA TBD reproxalap Aldeyra Allergic conjunctivitis; DED Ophthalmic Phase 3 – NDA TBD

resmetirom Madrigal/Roche NASH

Oral Phase 3 – NDA; Fast Track TBD RGX-121 Regenxbio Mucopolysaccharidosis II (MPS II; Hunter syndrome) Intracisternal Phase 3 – BLA; Fast Track; Orphan Drug TBD ridinilazole Summit C. difficile-associated diarrhea Oral Phase 3 – NDA; Fast Track; QIDP TBD roluperidone Minerva Schizophrenia Oral Phase 3 − NDA 08/22/2023 ropeginterferon alfa-2b Pharmaessentia Essential thrombocythemia SC Phase 3 – BLA; Orphan Drug TBD roxadustat AstraZeneca Anemia due to cytotoxic chemotherapy Oral Phase 3 – NDA TBD rozanolixizumab UCB Myasthenia gravis SC Phase 3 – BLA; Orphan Drug TBD

RSV vaccine (GSK3844766A)

RSV vaccine (JNJ-64400141)

GlaxoSmithKline RSV prevention (older adults) IM Phase 3 – BLA; Fast Track TBD

Janssen RSV prevention (older adults) IM Phase 3 – BLA; Breakthrough Therapy TBD

RSV vaccine (PF-06928316)

Pfizer RSV prevention (older adults, maternal immunization)

IM Phase 3 – BLA; Breakthrough Therapy; Fast Track

TBD ruxolitinib (deuterated) Concert Alopecia areata Oral Phase 3 – NDA; Breakthrough Therapy; Fast Track

TBD sabatolimab Novartis Myelodysplastic syndrome IV Phase 3 – BLA; Fast Track TBD saroglitazar magnesium Zydus Cadila Primary biliary cholangitis Oral Phase 3 – NDA; Fast Track; Orphan Drug TBD

seasonal influenza nanoparticle vaccine

Novavax Seasonal influenza prevention IM Phase 3 – BLA; Fast Track TBD sebetralstat Kalvista HAE

Oral Phase 3 – NDA; Fast Track TBD seladelpar Cymabay Primary biliary cholangitis Oral Phase 3 – NDA; Breakthrough Therapy; Orphan Drug

TBD seltorexant Janssen MDD Oral Phase 3 – NDA TBD sepofarsen Proqr Leber’s congenital amaurosis Intravitreal Phase 3 – NDA; Fast Track; Orphan Drug TBD

sotatercept Merck/Bristol-Myers Squibb

PAH

SC Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

TBD

sotrovimab Vir COVID-19

Oral Phase 3 – NDA; Orphan Drug TBD

IV Phase 3 – BLA TBD sparsentan Travere/BristolMyers Squibb Focal segmental glomerulosclerosis

SPK-8011 Genentech Hemophilia A

IV Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

IV Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

TBD

TBD tabelecleucel Atara Epstein-Barr virus-associated post-transplant lymphoproliferative disease

TAK-755 Takeda Thrombotic thrombocytopenic purpura (TTP)

tamibarotene Syros Myelodysplastic syndrome

IV Phase 3 – BLA; Fast Track; Orphan Drug TBD

Oral Phase 3 – NDA; Orphan Drug TBD

tanfanercept Hanall DED

Intravitreal Phase 3 – BLA TBD

Ophthalmic Phase 3 – BLA TBD tarcocimab tedromer Kodiak DME; Retinal vein occlusion-associated macular edema; Wet AMD

tebipenem pivoxil Spero UTI (complicated)

IV Phase 3 – BLA; Breakthrough Therapy; Orphan Drug

TBD

Oral Phase 3 – NDA; Fast Track; QIDP TBD tecarfarin Espero Anticoagulation Oral Phase 3 – NDA TBD tiragolumab Genentech Esophageal cancer; NSCLC

tiratricol Rare Thyroid Therapeutics Resistance to thyroid hormone type beta (RTH-b)

Oral Phase 3 – NDA; Fast Track; Orphan Drug; Rare Pediatric Disease

TBD tislelizumab Beigene Gastric cancer; HCC; NSCLC IV Phase 3 – BLA; Orphan Drug TBD tocilizumab (biosimilar to Genentech’s Actemra)

Bio-Thera Solutions/ Biogen RA; Polyarticular JIA; Systemic JIA IV Phase 3 – BLA TBD tominersen Genentech Huntington’s disease Intrathecal Phase 3 – NDA; Orphan Drug TBD

tovorafenib Day One Brain cancer

Oral Phase 3 – NDA; Breakthrough Therapy; Orphan Drug; Rare Pediatric Disease

Oral Phase 3 – NDA TBD

TBD tradipitant Vanda/Eli Lilly Atopic dermatitis; COVID-19; Emesis; Gastroparesis; Pruritus

travoprost implant Glaukos Glaucoma/ocular hypertension

Intraocular Phase 3 – NDA TBD tusamitamab ravtansine Sanofi NSCLC IV Phase 3 – BLA TBD udenafil Dong-A Socio Single ventricle heart disease after Fontan palliation

Oral Phase 3 – NDA; Orphan Drug TBD upifitamab rilsodotin Mersana

Ovarian cancer

Amgen PSO; PsA; CD; UC IV, SC Phase 3 – BLA TBD

IV Phase 3 – BLA; Fast Track TBD ustekinumab (biosimilar to Janssen’s Stelara®)

ustekinumab (biosimilar to Janssen’s Stelara)

Formycon

PSO; PsA; CD; UC IV, SC Phase 3 – BLA TBD

ustekinumab (biosimilar to Janssen’s Stelara)

Hikma

Intas PSO; PsA; CD; UC IV, SC Phase 3 – BLA TBD

PSO; PsA; CD; UC IV, SC Phase 3 – BLA TBD ustekinumab (biosimilar to Janssen’s Stelara)

vadadustat Akebia

Anemia due to CKD (dialysis-dependent, dialysis-independent)

Oral Phase 3 – NDA; Orphan Drug TBD

Oral Phase 3 – NDA TBD venglustat Sanofi Gaucher’s disease; GM2 gangliosidoses (TaySachs disease, Sandhoff disease, AB variant)

verbrinacogene setparvovec

Freeline Hemophilia B IV Phase 3 – BLA; Orphan Drug; RMAT TBD VGX-3100 therapeutic vaccine Inovio Cervical dysplasia (human papillovirus-positive) IM Phase 3 – BLA TBD

visomitin Mitotech DED Ophthalmic Phase 3 – NDA TBD wilfactin LFB von Willebrand disease IV Phase 3 – BLA; Orphan Drug TBD

xanomeline tartrate and trospium chloride Karuna Schizophrenia Oral Phase 3 – NDA TBD zanidatamab Zymeworks Gastric cancer IV Phase 3 – BLA; Fast Track; Orphan Drug TBD

zavegepant Biohaven/BristolMyers Squibb

adalimumab (Hulio; biosimilar to Abbvie’s Humira)

TBD

Migraine prevention Intranasal Phase 3 – NDA TBD zilucoplan UCB Myasthenia gravis SC Phase 3 – NDA; Orphan Drug TBD zolbetuximab Astellas Gastric cancer IV Phase 3 – BLA; Orphan Drug TBD zoliflodacin Entasis Gonorrhea Oral Phase 3 – NDA; Fast Track; QIDP TBD zuranolone Sage MDD; Post-partum depression Oral Phase 3 – NDA; Breakthrough Therapy; Fast Track

Phase 3 (Supplementals)

Viatris/Biocon Hidradenitis suppurativa; Uveitis SC Phase 3 – sBLA TBD

atezolizumab (Tecentriq®) Genentech SCCHN IV Phase 3 – sBLA TBD baricitinib (Olumiant) Eli Lilly JIA; Uveitis Oral Phase 3 – sNDA TBD benralizumab (Fasenra®) AstraZeneca ANCA-associated vasculitis; Bronchiectasis; Bullous pemphigoid; Chronic rhinosinusitis with nasal polyps (CRSwNP); Esophagitis

SC Phase 3 – sBLA; Orphan Drug TBD

brexpiprazole (Rexulti®) Otsuka Alzheimer’s disease; PTSD Oral Phase 3 – sNDA; Fast Track TBD

dupilumab (Dupixent®) Sanofi

Allergic fungal rhinosinusitis; Bullous pemphigoid; Chronic rhinosinusitis; COPD; Urticaria

SC Phase 3 – sBLA TBD

efgartigimod (Vyvgart®) Argenx ITP IV Phase 3 – sBLA; Orphan Drug TBD

empagliflozin (Jardiance®) Boehringer Ingelheim

ferric carboxymaltose (Injectafer®)

Diabetic nephropathy Oral Phase 3 – sNDA TBD

Daiichi Sankyo Anemia in heart failure IV Phase 3 – sNDA TBD

ferric derisomaltose (Monoferric®)

Aclaris Warts Topical Phase 3 – sNDA TBD

Pharmacosmos Anemia in heart failure IV Phase 3 – sNDA TBD guselkumab (Tremfya®) Janssen UC SC Phase 3 – sBLA TBD hydrogen peroxide (Eskata®)

immune globulin intravenous (human) 10% (Octagam®)

Octapharma COVID-19 IV Phase 3 – sBLA TBD inebilizumab-cdon (Uplizna®)

Horizon Immunoglobulin G4-related disease; Myasthenia gravis

Evofem Chlamydia trachomatis infection; Neisseria gonorrhoeae infection

Intravaginal Phase 3 – sNDA; Fast Track; QIDP TBD

IV Phase 3 – sBLA TBD L-lactic acid/citric acid/ potassium bitartrate (Phexxi®)

mepolizumab (Nucala®) GlaxoSmithKline COPD IV, SC Phase 3 – sBLA TBD meropenem/vaborbactam (Vabomere®) Melinta Bacteremia; HAP IV Phase 3 – sNDA; QIDP TBD nitazoxanide (Alinia®) Lupin COVID-19; Influenza Oral Phase 3 – sNDA TBD obeticholic acid (Ocaliva®) Intercept NASH Oral Phase 3 – sNDA; Breakthrough Therapy TBD odevixibat (Bylvay™) Albireo Alagille syndrome-related cholestatic pruritus Oral Phase 3 – sNDA; Orphan Drug TBD omalizumab (Xolair®) Genentech Food allergies SC Phase 3 – sBLA; Breakthrough Therapy TBD patisiran (Onpattro®) Alnylam Transthyretin amyloid cardiomyopathy (ATTR-CM, wild type or hereditary)

IV Phase 3 – sNDA; Orphan Drug TBD

Ipsen SCLC IV Phase 3 – sNDA; Fast Track; Orphan Drug TBD ravulizumab-cwvz (Ultomiris®)

pegylated liposomal irinotecan (Onivyde®)

IV, SC Phase 3 – sBLA TBD risankizumab-rzaa (Skyrizi®)

Alexion COVID-19; Dermatomyositis; Thrombotic microangiopathy; Neuromyelitis optica (Devic’s syndrome)

Abbvie UC IV, SC Phase 3 – sBLA TBD rituximab-arrx (biosimilar to Genentech’s Rituxan) (Riabni)

Amgen RA IV Phase 3 – sBLA TBD rivaroxaban (Xarelto®) Janssen COVID-19 Oral Phase 3 – sNDA TBD

NAME MANUFACTURER CLINICAL USE

FORM DEVELOPMENT

Atopic dermatitis Topical Phase 3 – sNDA TBD romiplostim (Nplate®) Amgen Chemotherapy-induced thrombocytopenia SC Phase 3 – sBLA; Orphan Drug TBD secukinumab (Cosentyx®) Novartis

roflumilast (Zoryve™) Arcutis

Hidradenitis suppurativa IV, SC Phase 3 – sBLA TBD tapinarof (Vtama®) Roivant

Atopic dermatitis Topical Phase 3 – sNDA TBD tezepelumab-ekko (Tezspire™)

AstraZeneca Nasal polyposis SC Phase 3 – sBLA TBD ticagrelor (Brilinta) AstraZeneca SCD Oral Phase 3 – sNDA TBD tirzepatide (Mounjaro™) Eli Lilly Obesity SC Phase 3 – sNDA; Fast Track TBD

upadacitinib (Rinvoq) Abbvie

Giant cell arteritis Oral Phase 3 – sNDA TBD

Complete Response Letter (CRL)

NAME MANUFACTURER CLINICAL USE

FORM DEVELOPMENT STATUS

DECISION

apomorphine infusion pump Supernus

Alvotech RA; AS; PSO; PsA; JIA; CD; UC SC CRL TBD

Parkinson’s disease SC CRL TBD adalimumab 100 mg/mL (biosimilar to Abbvie’s Humira)

pimavanserin (Nuplazid®) Acadia

Alzheimer’s diseaserelated hallucinations and delusions

Oral CRL TBD

taurolidine/citrate/heparin Cormedix

Reduction of catheterrelated bloodstream infections (CRBSIs) related to chronic hemodialysis

Breast cancer; Gastric/ gastroesophageal cancer IV CRL TBD

IV CRL TBD trastuzumab (biosimilar to Genentech’s Herceptin) Tanvex

GLOSSARY

6MWT 6 Minute Walking Test

ABSSSI Acute Bacterial Skin and Skin Structure Infection

ACEI Angiotensin-Converting Enzyme Inhibitor

ACR20 American College of Rheumatology 20% Improvement

ACR50 American College of Rheumatology 50% Improvement

ACR70 American College of Rheumatology 70% Improvement

ADC Antibody-Drug Conjugate

ADHD Attention Deficit Hyperactivity Disorder

ADL Activities of Daily Living

AED Anti-Epileptic Drug

ALK Anaplastic Lymphoma Kinase

ALL Acute Lymphoblastic Leukemia

ALS Amyotrophic Lateral Sclerosis

ALT Alanine Transaminase

AMD Age-Related Macular Degeneration

AML Acute Myeloid Leukemia

ANCA Antineutrophil Cytoplasmic Antibodies

ANDA Abbreviated New Drug Application

ARB Angiotensin II Receptor Blocker

ARNI Angiotensin Receptor II Blocker – Neprilysin Inhibitor

ART Antiretroviral Therapy

ARV Antiretroviral

AS Ankylosing Spondylitis

ASCVD Atherosclerotic Cardiovascular Disease

AST Aspartate Aminotransferase

BCG Bacillus Calmette-Guérin

BCVA Best Corrected Visual Acuity

BLA Biologics License Application

BMI Body Mass Index

BMT Bone Marrow Transplant

BPH Benign Prostatic Hyperplasia

BSA Body Surface Area

BsUFA Biosimilar User Fee Act

CABP Community Acquired Bacterial Pneumonia

CAP Community Acquired Pneumonia

CAR T Chimeric Antigen Receptor T Cell

CD Crohn's Disease

CDC Centers for Disease Control and Prevention

CF Cystic Fibrosis

CHF Congestive Heart Failure

CI Confidence Interval

CKD Chronic Kidney Disease

CLL Chronic Lymphocytic Leukemia

CML Chronic Myeloid Leukemia

CMS Centers for Medicare & Medicaid Services

CNS Central Nervous System

COPD Chronic Obstructive Pulmonary Disease

COVID-19 Coronavirus Disease 2019

CRC Colorectal Cancer

CRL Complete Response Letter

CRR Complete Response Rate

CSF Colony Stimulating Factor

CV Cardiovascular

CVD Cardiovascular Disease

DAS28-CRP Disease Activity Score-28 with C Reactive Protein

DCR Disease Control Rate

DEA Drug Enforcement Administration

DED Dry Eye Disease

DLBCL Diffuse Large B Cell Lymphoma

DMARD Disease Modifying Antirheumatic Drug

DMD Duchenne Muscular Dystrophy

DME Diabetic Macular Edema

DMT Disease Modifying Therapy

DNA Deoxyribonucleic Acid

DOR Duration of Response

DPI Dry Powder for Inhalation

DPP-4 Dipeptidyl Peptidase 4

DR Delayed-Release

EASI-75 Eczema Area and Severity Index ≥ 75% Reduction

ECOG Eastern Cooperative Oncology Group

EDSS Expanded Disability Status Scale

eGFR estimated Glomerular Filtration Rate

GLOSSARY continued

EGFR Epidermal Growth Factor Receptor

ER Extended-Release

ESA Erythropoietin Stimulating Agent

ESRD End-Stage Renal Disease

EUA Emergency Use Authorization

FDA Food and Drug Administration

FH Familial Hypercholesterolemia

FLT3 FMS-Like Tyrosine Kinase-3

G-CSF Granulocyte Colony Stimulating Factor

GI Gastrointestinal

GIST Gastrointestinal Stromal Tumor

GLP-1RA Glucagon-Like Peptide-1 Receptor Agonist

GM-CSF Granulocyte-Macrophage Colony Stimulating Factor

GVHD Graft Versus Host Disease

H Half

HAART Highly Active Antiretroviral Therapy

HAE Hereditary Angioedema

HAM-D Hamilton Depression Rating Scale

HAP Healthcare-Associated Pneumonia

Hb Hemoglobin

HbA1c Hemoglobin A1c

HBV Hepatitis B Virus

HCC Hepatocellular Carcinoma

HCP Healthcare Professional

HCV Hepatitis C Virus

HER Human Epidermal Growth Factor Receptor

HER2 Human Epidermal Growth Factor Receptor 2

HF Heart Failure

HFA Hydrofluoroalkane

HFpEF Heart Failure with preserved Ejection Fraction

HIT Heparin Induced Thrombocytopenia

HIV Human Immunodeficiency Virus

HIV-1 Human Immunodeficiency Virus-1

HPV Human Papilloma Virus

HR Hazard Ratio

HSCT Hematopoietic Stem Cell Transplant

HSV Herpes Simplex Virus

HTN Hypertension

IBS Irritable Bowel Syndrome

IBS-C Irritable Bowel Syndrome, Constipation Predominant

ICU Intensive Care Unit

IGA Investigator's Global Assessment

IL-12 Interleukin-12

IL-17 Interleukin-17

IL-23 Interleukin-23

IM Intramuscular

IR Immediate-Release

IRB Internal Review Board

ITP Immune Thrombocytopenic Purpura

ITT Intent-To-Treat

IV Intravenous

JIA Juvenile Idiopathic Arthritis

LDL Low-Density Lipoprotein

LDL-C Low-Density Lipoprotein Cholesterol

LVEF Left Ventricular Ejection Fraction

mAb Monoclonal Antibody

MACE Major Adverse Cardiovascular Events

MADRS Montgomery – Åsberg Depression Rating Scale

MAOI Monoamine Oxidase Inhibitor

MDD Major Depressive Disorder

MDI Metered Dose Inhaler

MDR Multi-Drug Resistant

mITT modified Intent-To-Treat

MRI Magnetic Resonance Imaging

MRSA Methicillin-Resistant Staphylococcus Aureus

MS Multiple Sclerosis

N/A Not Applicable

NASH Non-Alcoholic Steatohepatitis

NCCN National Comprehensive Cancer Network

NCT National Clinical Trials

NDA New Drug Application

NHL Non-Hodgkin Lymphoma

NIAID National Institute of Allergy and Infectious Diseases

NSAID Non-Steroidal Anti-Inflammatory Drug

NSCLC Non-Small Cell Lung Cancer

NYHA New York Heart Association

ODT Orally Disintegrating Tablet

OR Odds Ratio

ORR Overall/Objective Response Rate

GLOSSARY continued

OS Overall Survival

OTC Over-the-Counter

PAH Pulmonary Arterial Hypertension

PARP Poly(ADP-ribose) Polymerase

PAS Prior Approval Supplement

PASI Psoriasis Area and Severity Index

PASI 50 Psoriasis Area and Severity Index 50% Reduction

PASI 75 Psoriasis Area and Severity Index 75% Reduction

PASI 90 Psoriasis Area and Severity Index 90% Reduction

PASI 100 Psoriasis Area and Severity Index 100% Reduction

PCI Percutaneous Coronary Intervention

PCSK9 Proprotein Convertase Subtilisin Kexin 9

PD-1 Programmed Death Protein 1

PD-L1 Programmed Death-Ligand 1

PDUFA Prescription Drug User Fee Application

PFS Progression-Free Survival

PGA Physician Global Assessment

PHI Primary Humoral Immunodeficiency

PI3K Phosphatidylinositol-3-kinase

PNH Paroxysmal Nocturnal Hemoglobinuria

PsA Psoriatic Arthritis

PSO Plaque Psoriasis

PTCA Percutaneous Transluminal Coronary Angioplasty

PTSD Post-Traumatic Stress Disorder

Q Quarter

QIDP Qualified Infectious Diseases Product

QOL Quality of Life

R/R Relapsed or Refractory

R-CHOP Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

RA Rheumatoid Arthritis

RBC Red Blood Cell

RCC Renal Cell Carcinoma

REMS Risk Evaluation and Mitigation Strategy

RMAT Regenerative Medicine Advanced Therapy

RNA Ribonucleic Acid

RRR Relative Risk Reduction

RSV Respiratory Syncytial Virus

RTOR Real-Time Oncology Review

RVO Retinal Vein Occlusion

SARS-CoV-2 Severe Acute Respiratory SyndromeAssociated Coronavirus-2

sBLA supplemental Biologics License Application

SC Subcutaneous

SCCHN Squamous Cell Cancer of the Head and Neck

SCD Sickle Cell Disease

SCLC Small Cell Lung Cancer

SCT Stem Cell Transplant

SGLT2 Sodium-Glucose Co-Transporter 2 SL Sublingual

SLE Systemic Lupus Erythematosus

SLL Small Lymphocytic Lymphoma

sNDA supplemental New Drug Application

SNRI Serotonin and Norepinephrine Reuptake Inhibitor

SOC Standard of Care

sPGA static Physician Global Assessment

SR Sustained-Release

SSRI Selective Serotonin Reuptake Inhibitor

SSSI Skin and Skin Structure Infection

T1DM Type 1 Diabetes Mellitus

T2DM Type 2 Diabetes Mellitus

TBD To Be Determined

TEAE Treatment-Emergent Adverse Event

TNBC Triple Negative Breast Cancer

TNF Tumor Necrosis Factor

TNFα Tumor Necrosis Factor-alpha

UA Unstable Angina

UC Ulcerative Colitis

US United States

UTI Urinary Tract Infection

VAS Visual Analog Scale

VEGF Vascular Endothelial Growth Factor

VTE Venous Thromboembolism

WBC White Blood Cell

WHO World Health Organization

XR Extended-Release

INTO

& TRADITIONAL