Katherine E. Rebello, PharmD Clinical Project Manager
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 2027. 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 2023, the FDA has approved 43 novel drugs, compared to only 28 about the same time last year. For the remainder of the year, 24 notable drugs filed with the agency are profiled, each with an anticipated FDA decision in 2023.
While numbers do not tell the entire story, they do represent significant innovation in patient care and advance public health for the American public.
ON THE HORIZON
As we look ahead, there is a continued trend towards the approval of specialty medications and drugs for rare conditions, with 69% and 34% of approvals expected, respectively, for agents with applications submitted to the FDA. There are 2 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. A new dual-acting option for obesity, the first ever treatment for NASH, new oral options for DMD and schizophrenia, a topical formulation for molluscum contagiousum, and a once-weekly insulin are expected. Approval of 2 new gene therapies for hemophilia A and B and a self-administered intranasal flu vaccine are on the horizon. Moreover, sprouting products for cardiology and Alzheimer's disease are being actively monitored through MRx Pipeline. Other noteworthy pipeline trends to watch include the development of complex therapies, cell and gene therapies “CGT,” oncology, immunology, and therapeutic options for ultra-rare hereditary diseases.
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.
Objective evidence-based methodology was used to identify the Deep Dive drugs 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.
Specialty drug names appear in magenta throughout the publication.
Idorsia
PROPOSED INDICATIONS
Resistant hypertension
CLINICAL OVERVIEW
Aprocitentan is a dual endothelin receptor antagonist.
The 3-part, phase 3 PRECISION trial (NCT03541174) evaluated aprocitentan in 730 adults with a sitting SBP ≥ 140 mm Hg despite standard background therapy (3 antihypertensive agents, including a diuretic). Many patients enrolled had comorbidities including diabetes, CKD, obesity, and congestive HF. In part 1 (double-blind), patients were randomized 1:1:1 to once daily aprocitentan 12.5 mg, aprocitentan 25 mg, or placebo for 4 weeks. A significant reduction in the primary endpoint of LS mean change in office SBP at week 4 was demonstrated with aprocitentan 12.5 mg and 25 mg compared to placebo (placebo-adjusted change, -3.8 mm Hg and -3.7 mm Hg, respectively; p<0.005 for both). A reduction in office DBP was also seen with each dose compared to placebo (placebo-adjusted change, -3.9 mm Hg and -4.5 mm Hg, respectively). In part 2 (patient-blinded), all patients received aprocitentan 25 mg (n=704) and the SBP and DBP reductions seen with aprocitentan were maintained for 32 weeks. In part 3 (double-blind), patients were re-randomized 1:1 to continue aprocitentan 25 mg or switch to placebo (withdrawal) for 12 weeks. Among patients who were switched to placebo, the office SBP and DBP increased significantly (5.8 mm Hg and 5.2 mm Hg, respectively; p<0.001 for both) after 4 weeks compared to those who continued aprocitentan. Dose-dependent mild to moderate fluid retention was reported with aprocitentan.
PLACE IN THERAPY
According to a 2018 AHA Scientific Statement, an estimated 10.3 million (19.7%) adults in the U.S. have apparent resistant hypertension, defined as failure to achieve target BP (130/80 mm Hg) despite treatment with 3 antihypertensive medications with complementary mechanisms of action, with 1 being a diuretic, or when a patient requires ≥ 4 medications to achieve the desired BP. Patients with resistant hypertension are at increased risk of CHD, stroke, PAD, HF, ESRD, and all-cause mortality. Resistant hypertension is more likely to affect Blacks or African Americans and individuals with advanced age, obesity, CKD or diabetes.
Lifestyle intervention (e.g., weight loss, sodium restriction, exercise) and addressing causes of secondary hypertension are important for managing hypertension. Empirical pharmacotherapy combines medications with complementary mechanisms and includes a diuretic, a calcium channel blocker, and a renin-angiotensinaldosterone system blocker (ACEI or ARB). If BP goals are not met with 3 antihypertensive agents, stepwise additions of the following agents are made: mineralocorticoid receptor antagonist, beta-blocker and hydralazine.
The endothelin-1 (ET-1) peptide, produced by endothelial cells, is a potent vasoconstrictor and contributes to the regulation of sodium and water in the kidneys. ET-1 expression is amplified in patients with severe hypertension and is involved in BP elevation and vascular hypertrophy. Aprocitentan inhibits the binding of ET-1 to the ETA and ETB receptors. In clinical trials, significant changes in BP were observed within 14 days of starting aprocitentan. If approved, aprocitentan will be the first dual endothelin receptor antagonist to treat resistant hypertension, a condition that is lacking therapeutic options. Notably, aprocitentan has not been evaluated for its effect on CV outcomes. In addition, aprocitentan is an active metabolite of macitentan (Opsumit®) that is indicated in patients with PAH. Macitentan carries a boxed warning for embryo-fetal toxicity; it remains to be seen if aprocitentan will carry this warning.
FDA APPROVAL TIMELINE
December 19, 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $1 $11 $28 $52 $74
INFECTIOUS DISEASE
Ligand
PROPOSED INDICATIONS
Molluscum contagiosum (MC)
CLINICAL OVERVIEW
Berdazimer is a topical nitric oxide-releasing antiviral.
The randomized, double-blind, vehicle-controlled, phase 3 B-SIMPLE4 trial (NCT04535531) evaluated berdazimer 10.3% gel in 891 immunocompetent patients ≥ 6 months of age with MC that was not sexually transmitted or in the periocular area. The study revealed significantly more patients treated with berdazimer achieved the primary endpoint of complete clearance of all MC lesions at week 12 compared to patients who received vehicle (43.5% versus 24.6%, respectively; p<0.001). A significant difference between the groups was observed as early as week 4. Notably, in the randomized, double-blind, phase 3 B-SIMPLE1 (NCT03927716; n=352) and B-SIMPLE2 (NCT03927703; n=355) trials in patients ≥ 6 months of age with MC, berdazimer did not demonstrate a statistically significant difference from vehicle in the primary endpoint of complete clearance of treatable MC lesions at week 12 (B-SIMPLE1, 25.8% versus 21.6%, respectively [p=0.375]; B-SIMPLE2, 30% versus 20.3%, respectively [p=0.062]). In all 3 trials, berdazimer was well tolerated. The most common TEAEs were application site pain and erythema. Most were mild in severity.
Berdazimer 10.3% gel was administered topically by the patient or caregiver once daily as a thin layer to the top of all MC lesions identified at baseline and any new lesions that arose, for a maximum of 12 weeks.
PLACE IN THERAPY
MC is a highly contagious viral skin infection caused by molluscipoxvirus that affects an estimated 6 million people in the U.S. annually. Small, raised, pus-filled lesions 2 to 5 mm in size appear throughout the body (except hands and feet) and may itch or be tender. MC is transmitted by direct contact with lesions or contaminated clothing, linen, sports equipment and toys. MC is most commonly seen in children 1 to 14 years of age and in people with weakened immune systems (e.g., HIV-1-positive). MC is particularly reported in crowded, warm, humid conditions.
MC lesions typically resolve within 6 to 12 months, but may take as long as 4 to 5 years to clear if left untreated. Reasons to treat MC include: immunocompromised status, genital MC lesions, underlying atopic condition, transmission or autoinoculation prevention, scarring prevention, and elimination of social stigma. Cryotherapy, curettage and laser therapy have been used by HCPs to remove MC lesions. In July 2023, cantharidin 0.7% topical solution (Ycanth™) became the first FDA-approved medication to treat MC. The topical blistering agent is indicated for use in patients ≥ 2 years of age and is administered by a trained HCP every 3 weeks, as needed, for up to 4 treatments. Other agents that have been used off-label include oral cimetidine and the topical products podophyllotoxin, imiquimod (not recommended in children), retinoids, salicylic acid, iodine and potassium hydroxide. Treatment of MC in immunocompromised patients (e.g., HIV-1-positive) may be a challenge, and immune boosting therapies have been shown to be effective.
If approved, berdazimer will be a first-in-class, nitric oxide-releasing antiviral treatment for MC. It will also be the first FDA-approved agent for topical home-administration and may be a more convenient alternative to HCP-administered cantharidin (Ycanth). In non-comparative trials, the percentage of patients who experienced complete clearance of MC lesions was 43.5% with berdazimer (B-SIMPLE-4) and 46% to 54% with cantharidin. The phase 3 studies for both products did not include immunocompromised patients.
Eplontersen is a ligand-conjugated antisense (LICA) agent that inhibits the production of the transthyretin (TTR) protein. Eplontersen shares the same nucleotide sequence as inotersen that is FDA-approved for ATTRv-PN.
The open-label, phase 3 NEURO-TTRansform study evaluated eplontersen in 144 adults with hATTRv-PN who could ambulate independently or with support. Eplontersen treatment demonstrated significant benefit in 3 co-primary endpoints at 66 weeks compared to data from an external placebo group. This included a reduction from baseline in serum TTR concentration (LS mean reduction, 81.7% versus 11.2%, respectively [p<0.0001]); halting of disease progression based on the modified Neuropathy Impairment Score +7 (mNIS+7) (LS mean increase, 0.3 versus 25.1, respectively [p<0.0001]); and improved QOL based on the Norfolk QOL Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) score (LS mean change, -5.5 versus +14.2, respectively [p<0.0001]). Among patients treated with eplontersen in the overall study population, 47% showed neuropathy improvement and 58% reported QOL improvement compared to 17% and 20%, respectively, in the external placebo group. Benefits from eplontersen were seen as early as 35 weeks and were maintained at 85 weeks. Eplontersen was well tolerated, with TEAEs comparable to the external placebo group. Two deaths occurred in the eplontersen group due to hATTR-PN amyloidosis sequelae.
Eplontersen was administered SC at a dose of 45 mg once every 4 weeks.
PLACE IN THERAPY
ATTRv-PN is a rare, progressive, fatal neurodegenerative condition caused by mutations in the TTR gene. It is characterized by accumulation of abnormal amyloid proteins in organs and tissues that lead to sensory and motor polyneuropathy. In the U.S., an estimated 1 in 100,000 individuals are affected by hATTR amyloidosis. Symptoms usually become evident between 20 and 50 years of age. Peripheral sensorimotor nerves and nerves of the upper and lower limbs may be affected in a symmetric manner. CNS involvement may be observed in advanced stages. If left untreated, death occurs within 7 to 12 years after diagnosis.
The TTR proteins are primarily produced in the liver. Prior to the approval of the TTR-directed antisense agents, which are inotersen (Tegsedi®; 2018), patisiran (Onpattro®; 2018), and vutrisiran (Amvuttra®; 2022), liver transplantation was the only DMT available for hATTRv-PN.
If approved, eplontersen will be the fourth TTR-targeting treatment available in the U.S. for hATTRv-PN. In the clinical trial, it was well tolerated and was shown to halt progression of neuropathy, reduce TTR protein concentrations, and improve QOL. If approved, eplontersen may provide a convenient every-4-week selfadministered option. In comparison, inotersen is self-administered as weekly SC injections, and vutrisiran and patisiran are HCP-administered as an every-3-month SC injection and every-3-week IV infusion, respectively. Moreover, while inotersen carries boxed warnings for thrombocytopenia and glomerulonephritis and is available only through a REMS program, these TEAEs have not been reported with eplontersen.
FDA APPROVAL TIMELINE
December 22, 2023
Orphan Drug
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $1 $39 $85 $189 $261
Merck
PROPOSED INDICATIONS
Chronic cough
CLINICAL OVERVIEW
Gefapixant is an oral selective antagonist of the P2X3 receptor that is found on sensory nerve fibers in the lining of the airway.
The randomized, double-blind, placebo-controlled phase 3 COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) trials evaluated gefapixant in a total of 2,044 adults with refractory chronic cough or unexplained chronic cough for a mean duration of 11 years. Gefapixant 45 mg demonstrated a statistically significant reduction in 24-hour cough frequency (primary endpoint) compared to placebo at week 12 in COUGH-1 (reduction relative to placebo, 18.45%; p=0.041), and at week 24 in COUGH-2 (reduction relative to placebo, 14.64%; p=0.031). A clinically important level of improvement in QOL as related to cough was reported by 77.1% of patients who received gefapixant 45 mg. A gefapixant 15 mg twice daily dose was also evaluated in the studies but did not demonstrate a significant benefit compared to placebo. Gefapixant was associated with taste disturbances. In COUGH-1 and COUGH-2, 15% and 20% of patients treated with gefapixant 45 mg, respectively, discontinued the trial due to TEAEs.
Gefapixant 45 mg was administered orally twice daily.
PLACE IN THERAPY
Chronic cough is defined as cough lasting > 8 weeks. Chronic cough is considered either refractory chronic cough when it does not respond to treatment of underlying conditions (e.g., asthma or GERD), or unexplained chronic cough when there is no identifiable underlying condition. Patients may have a heightened cough reflex that is triggered by low levels of thermal, chemical or mechanical stimuli. Chronic cough of this type is usually dry or minimally productive. Patients often report musculoskeletal chest pains, sleep disturbance and hoarse voice. In addition, blackouts, stress incontinence and vomiting can occur in more serious cases. It is estimated that chronic cough affects 5% to 10% of adults and is more common among females and people in their 50s and 60s.
Chronic cough that is secondary to upper and lower airway conditions (e.g., COPD, asthma, allergies, rhinitis), GERD, obstructive sleep apnea, medications or smoking may resolve when the underlying cause has been identified and treated. In general, adequate fluid intake, air humidification, avoidance of irritants, and OTC antitussive agents may provide cough relief. However, treatments for unexplained or refractory chronic cough are lacking. The American College of Chest Physicians (CHEST) suggests a therapeutic trial of multimodality speech pathology therapy for unexplained chronic cough. Gabapentin may be tried after review of risks and benefits of therapy with the patient.
Extracellular adenosine triphosphate (ATP) plays a key role in airway inflammation and has become a potential target for treating refractory chronic cough. Upon airway inflammation, irritation or mechanical stress/injury, cells lining the airway release ATP. Extracellular ATP then binds to and activates P2X3 receptors on vagal afferent nerves of the airway and induces the cough reflex. Gefapixant is a first-in-class P2X3 receptor antagonist that has demonstrated 15% to 18% reduction in cough frequency (relative to placebo) through reduction of sensory nerve activation in patients with refractory or unexplained chronic cough. In studies, gefapixant has been associated with taste disturbances. If approved, it will be the first medication in the U.S. indicated specifically for refractory or unexplained chronic cough.
FDA APPROVAL TIMELINE
December 27, 2023 (An FDA advisory committee review is planned for November 17, 2023.)
FINANCIAL FORECAST (reported in millions)
The projected total U.S. sales for gefapixant are not available.
PROPOSED INDICATIONS
Duchenne muscular dystrophy (DMD)
CLINICAL OVERVIEW
Givinostat is a histone deacetylases (HDACs) inhibitor.
The multinational, double-blind, placebo-controlled, phase 3 EPIDYS (NCT02851797) trial evaluated givinostat in 179 ambulant boys ≥ 6 years of age with DMD who were on stable corticosteroid therapy for ≥ 6 months. The mean age was 9.8 years. Patients were randomized 2:1 to oral givinostat or placebo for 18 months. The primary endpoint was change from baseline to 18 months in time required to climb 4 standard stairs in the target population (n=120) which included boys with baseline vastus lateralis muscle fat fraction (VL MFF) between >5% and ≤ 30% based on magnetic resonance spectroscopy (MRS) assessment. The study demonstrated a slower decline to climb 4 stairs with givinostat compared to placebo (difference versus placebo, 1.78 seconds; p=0.0345). Significant improvements in the secondary endpoints of North Star Ambulatory Assessment (NSAA) (p=0.02) and the time to rise (TTR) test were also reported with givinostat compared to placebo. In addition, data demonstrated that givinostat led to a significant delay in fat infiltration by approximately 30% (difference versus placebo, -2.9%; nominal p=0.035). The most common adverse events reported with givinostat were GI disturbances, thrombocytopenia, pyrexia and hypertriglyceridemia.
Givinostat oral suspension was administered as a weight-based dose twice daily.
PLACE IN THERAPY
DMD is a rare, X-linked neuromuscular disorder characterized by progressive muscle degeneration and weakness. An estimated 400 to 600 boys are born with DMD each year in the U.S. In DMD, gene mutations lead to a lack of functional dystrophin protein involved in maintaining muscle fiber integrity. Onset of signs and symptoms of DMD occurs between 3 to 5 years of age. Most boys affected lose the ability to walk by age 12. Moreover, death due to respiratory or cardiac failure typically occurs by the early 30s. Select corticosteroids (prednisone) have been used historically to treat DMD, and deflazacort (Emflaza®) is the only steroid FDA-approved for DMD. Corticosteroids may be used in combination with other agents for DMD, including casimersen (Amondys 45), eteplirsen (Exondys 51), golodirsen (Vyondys 53) and viltolarsen (Viltepso®). While corticosteroids have been a SOC in DMD to delay progression of muscle weakness and improve respiratory function, their use is associated with side effects such as weight gain, slowed growth trajectories, bone fractures and cataracts. Recently, Sarepta’s delandistrogene moxeparvovec-rokl (Elevydis) became the first gene therapy approved, via Accelerated Approval, to treat DMD. In addition, Santhera’s oral steroid vamorolone was submitted to the FDA for DMD, with an anticipated FDA decision by October 26, 2023.
HDAC enzymes alter the 3-dimensional folding of DNA and thereby prevent gene translation. In DMD, higher than normal HDAC activity may prevent muscle regeneration and elicit inflammation. In clinical trials, HDAC inhibition by givinostat slowed disease progression, significantly increased muscle mass, and significantly reduced fibrotic tissue, muscle tissue necrosis and fatty replacement. If approved, givinostat will be an additional option in the growing armamentarium for DMD.
FDA APPROVAL TIMELINE
December 21, 2023
Fast Track
Orphan Drug
Priority Review
RPD
FORECAST (reported in millions) Year 2023 2024 2025 2026 2027
PROPOSED INDICATIONS
Non-alcoholic steatohepatitis (NASH) with liver fibrosis
CLINICAL OVERVIEW
Resmetirom is a thyroid hormone receptor (THR)-β selective agonist. It works by treating the underlying disease in patients with NASH by decreasing liver fat, thereby reducing lipotoxicity to induce NASH resolution.
The double-blind, phase 3 MAESTRO-NASH trial (NCT03900429) evaluated resmetirom in adults with biopsyconfirmed NASH with fibrosis. Patients were randomized 1:1:1 to receive resmetirom 80 mg, resmetirom 100 mg or placebo. After 52 weeks, significantly more patients treated with resmetirom experienced improvement in the co-primary endpoints compared to placebo:
NASH resolution (ballooning 0, inflammation 0,1) with ≥2-point reduction in NAS and no worsening of fibrosis
Improvements in fibrosis and NASH were seen regardless of gender, age, T2DM status, baseline fibrosis stage or NAS (< 6, ≥ 6). Atherogenic lipids and lipoproteins (e.g., LDL-C and triglycerides) also decreased with resmetirom treatment. Resmetirom was generally well tolerated. The most common TEAEs were mild, transient diarrhea and nausea reported at therapy initiation. No cases of drug-induced liver injury were reported. The MAESTRO-NASH-OUTCOMES study is underway to evaluate resmetirom 80 mg on liver-related outcomes in adults with well-compensated (Child-Pugh A) NASH cirrhosis plus all-cause mortality and may serve as the confirmatory data for potential full approval. Study completion is expected in 2025.
Resmetirom was administered orally once daily.
PLACE IN THERAPY
NASH is an advanced form of NAFLD. According to the NIH, an estimated 24% of adults in the U.S. have NAFLD, and approximately 1.5% to 6.5% have NASH. NASH is characterized by accumulation of fat in the liver (steatosis), liver inflammation, hepatocyte injury (ballooning), with or without fibrosis, and ultimately cirrhosis. NASH is a leading cause of liver cancer and the second most common indication for liver transplantation. The condition is closely associated with metabolic disorders, such as obesity, metabolic syndrome and diabetes. CVD is also associated with NASH and is a leading cause of death among patients with NASH, particularly in those with fibrosis stage ≥ 2. NASH can occur at any age, but is typically diagnosed between the ages of 40 and 60 years, when irreversible liver damage becomes evident. Moreover, incidence of NASH is rising in pediatrics, due in part to an increase in childhood obesity.
There are no FDA-approved drugs to treat NASH. There have been setbacks in the development of medications to treat NASH, including the failure of Intercept’s obeticholic acid (Ocaliva®) to receive FDA approval for the condition, and the sponsor’s subsequent suspension of NASH activity. Current treatment consists of lifestyle management (weight loss, exercise, alcohol avoidance) as well as management of diabetes, hyperlipidemia and hypertension. If approved, resmetirom will be the first medication available in the U.S. to treat NASH. In the phase 3 trial, its use led to resolution of NASH and reduction of liver fibrosis, both surrogate endpoints that the FDA proposed as being reasonably likely to predict clinical benefit and which would support Accelerated Approval. Resmetirom is also in phase 3 trials for NAFLD.
resmetirom
FDA APPROVAL TIMELINE
March 14, 2024 (No FDA advisory committee review of resmetirom is currently planned.)
TAK-755 is a recombinant disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) protein.
An open-label, phase 3 trial (NCT03393975) evaluated TAK-755 in 38 patients 0 to 70 years of age with cTTP. Patients were randomized 1:1 to TAK-755 or SOC (e.g., plasma-based therapies) during months 1 through 6 (period 1), after which both groups were switched to the alternate treatment during months 7 through 12 (period 2). Following that, all patients received TAK-755 during months 13 through 18 (period 3). An interim analysis included data from 38 patients who were 12 to 58 years of age and had a mean TAK-755 exposure of 13.2 months. Data revealed that zero acute thrombotic thrombocytopenic purpura (TTP) episodes occurred during TAK-755 treatment and 1 event occurred during SOC treatment. TEAEs were reported in 10.3% of patients during TAK-755 treatment and 50% during SOC treatment. No drug neutralizing antibodies toward TAK-755 were detected. Pharmacokinetic characteristics were also assessed after a single infusion of TAK-755 in 36 patients ≥ 12 years of age and revealed an ADAMTS13 activity level 5 times higher in patients treated with TAK-755 compared to those given plasma-based therapy (maximum serum concentration, 100% versus 19%, respectively). Comparable results were reported in an open-label, phase 3b continuation study (NCT04683003).
In the phase 3 trials, TAK-755 was administered as 40 IU/kg IV every week or every other week, based on the patient’s regimen at enrollment.
PLACE IN THERAPY
cTTP is an ultra-rare inherited condition affecting approximately 1 in 1,000,000 individuals. It is characterized by chronic microvascular thrombosis. cTTP has been associated with several ADAMTS13 gene mutations that lead to a deficiency of the ADAMTS13 enzyme, a von Willebrand factor (VWF)-cleaving protein. Signs and symptoms of cTTP typically present during childhood but can start at any age, most notably during pregnancy. Disease complications include ischemic injury of the brain, heart and kidneys, with a mortality rate of > 90% if left untreated.
Treatment for cTTP focuses on replacement of the ADAMTS13 enzyme, usually by way of IV infusion of fresh-frozen plasma (FFP). Prophylactic plasma transfusion is recommended during pregnancy; however, a watch-and-wait approach may be taken outside of pregnancy. If approved, TAK-755 will be the first and only pharmacological treatment that replenishes ADAMTS13, thereby addressing the underlying cause of cTTP. In clinical trials, this enzyme replacement therapy demonstrated a tolerable safety profile and efficacy in preventing acute TTP events. TAK-755 is also being evaluated for immune-mediated TTP (phase 2b), acquired TTP (phase 2), and SCD (phase 2.
FDA APPROVAL TIMELINE
November 16, 2023 Fast Track Orphan Drug
Priority Review
FINANCIAL FORECAST (reported in millions)
RPD
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $5 $32 $76 $148 $213
Astellas
PROPOSED INDICATIONS
Gastric or gastroesophageal junction (G/GEJ) adenocarcinoma that is locally advanced unresectable or metastatic, HER2-negative, and is CLDN18.2-positive as 1st-line treatment
CLINICAL OVERVIEW
Zolbetuximab is a chimeric IgG1 monoclonal antibody. It binds to the transmembrane protein Claudin-18 isoform 2 (CLDN18.2) on the tumor surface and activates antibody- and complement-dependent cytotoxicity.
Zolbetuximab has been evaluated in 2 double-blind, phase 3, clinical trials, SPOTLIGHT (NCT03504397) and GLOW (NCT03653507), in adults with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic G/GEJ adenocarcinoma. In SPOTLIGHT, 565 patients were randomized 1:1 to zolbetuximab or placebo; each was added to mFOLFOX6 (folinic acid + 5-FU + oxaliplatin) chemotherapy. At a median follow-up of approximately 12 months, the median PFS (primary endpoint) was 10.61 months with zolbetuximab and 8.67 months with placebo (HR, 0.751; p=0.0066). The OS was 18.23 months with zolbetuximab and 15.54 months with placebo (HR, 0.75; p=0.0053), and ORR was 48% in each group. In GLOW, 507 patients were randomized to zolbetuximab or placebo; each was added to CAPOX (oral capecitabine + oxaliplatin) chemotherapy. The study demonstrated a significantly longer median PFS (primary endpoint) with zolbetuximab compared to placebo (8.21 versus 6.8 months, respectively; HR, 0.687; p=0.0007). OS was also significantly longer with zolbetuximab (14.39 versus 12.16 months, respectively; HR, 0.771; p=0.0118). Further, among patients with measurable disease, the ORR was 53.8% and 48.8% with zolbetuximab and placebo, respectively. In both trials, the most common TEAEs were nausea, vomiting and decreased appetite. Grade ≥ 3 TEAEs were reported with zolbetuximab and placebo (SPOTLIGHT, 87% versus 78%, respectively; GLOW, 72.8% versus 69.9%, respectively) and included nausea, vomiting and decreased appetite. Treatment-related death occurred in 2% and 1% of patients in the SPOTLIGHT zolbetuximab and placebo groups, respectively, and in 2.4% and 2.8% of the GLOW zolbetuximab and placebo groups, respectively.
Zolbetuximab was infused IV as an 800 mg/m2 loading dose, followed by 600 mg/m2 every 3 weeks.
PLACE IN THERAPY
Gastric cancer (GC) risks include Helicobacter pylori infection, tobacco smoking, high salt intake, and high alcohol consumption. In the U.S., the incidence of GC is declining, due in part to a decrease in H. pylori infection and improved food preservation; however, data suggest that the incidence of early-onset GC is rising. It is estimated that 26,500 new cases of GC will be diagnosed, and 11,130 deaths will occur due to the condition in the U.S. in 2023. Advanced GC has a high frequency of recurrence and metastasis and a poor prognosis. The preferred 1st-line chemotherapy for unresectable locally advanced or metastatic GC is the combination of a fluoropyrimidine (5-FU or capecitabine) and oxaliplatin. Depending on tumor characteristics, targeted agents such as trastuzumab (HER2-positive) and checkpoint inhibitors (PD-L1 combined positive score [CPS] ≥ 5; MSI-H/dMMR) may be added. However, an unmet need still remains in the GC space.
CLDN18.2 is a tight junction protein expressed exclusively in healthy gastric mucosa cells and is retained in gastric tumor cells making it a potential target for GC treatment. Zolbetuximab is a first-in-class CLDN18.2directed antibody. In clinical trials, when added to SOC chemotherapy regimens, it significantly prolonged PFS and OS compared to chemotherapy alone. If approved, zolbetuximab may help fulfill this unmet need in 1stline GC treatment. The agent is also being evaluated for pancreatic cancer as a CLDN18.2-targeting therapy.
FDA APPROVAL TIMELINE
January 12, 2024 Orphan Drug Priority Review RTOR
FINANCIAL FORECAST (reported in millions) Year 2023 2024 2025
Biosimilars
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 by the sponsor 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 biologic 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. In December 2022, the FDA announced a pilot regulatory science program that focuses on advancing the development of interchangeable products and improving the efficiency of biosimilar product development. The Purple Book is an FDA database of licensed biological products that lists biosimilar and interchangeable products. The FDA has approved 6 biosimilars for interchangeability to their reference product: adalimumab-adbm (Cyltezo®), adalimumab-afzb (Abrilada™), insulin glargine-yfgn (Semglee®), insulin glargineaglr (Rezvoglar™), ranibizumab-eqrn (Cimerli™) and ranibizumab-nuna (Byooviz™).
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. Historically, the FDA 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 U.S. market for biosimilar entry; however, patent litigation has resulted in significant launch delays of FDA-approved biosimilars. In June 2017, the U.S. 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 health care costs.
To date, a total of 43 biosimilars have received FDA approval. Of these, 37 have entered the market.
APPROVED BIOSIMILARS
Brand Name (Nonproprietary name)
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)
Retacrit® (epoetin alfa-epbx)
Fulphila® (pegfilgrastim-jmdb)
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)
Sandoz March 2015
Pfizer April 2016
Sandoz August 2016
Amgen September 2016
Merck/Organon May 2017
Boehringer Ingelheim August 2017
Amgen September 2017
Pfizer December 2017
Mylan/Biocon December 2017
Pfizer/Vifor/ Hospira May 2018
Mylan/Biocon June 2018
Pfizer July 2018
Sandoz October 2018
Coherus November 2018
Cephalon/Teva November 2018
Teva December 2018
Merck January 2019
Pfizer March 2019
Samsung Bioepis April 2019
Amgen June 2019
Pfizer June 2019
Organon July 2019
Pfizer July 2019
Pfizer November 2019
(Manufacturer)
Neupogen® (Amgen)
Remicade® (Janssen)
Enbrel® (Amgen)
Humira® (Abbvie)
Remicade (Janssen)
Humira (Abbvie)
Avastin® (Genentech)
Remicade (Janssen)
Herceptin® (Genentech)
Epogen® (Amgen) Procrit® (Janssen)
Neulasta® (Amgen)
Neupogen (Amgen)
(only HCF) Humira (Abbvie)
Neulasta (Amgen)
Rituxan® (Genentech)
Herceptin (Genentech)
Herceptin (Genentech)
Herceptin (Genentech)
Enbrel (Amgen)
Herceptin (Genentech)
Avastin (Genentech)
Humira (Abbvie)
Rituxan (Genentech)
Humira (Abbvie)
Brand Name (Nonproprietary name)
Ziextenzo® (pegfilgrastim-bmez)
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)
Idacio® (adalimumab-aacf)
Yuflyma®* (adalimumab-aaty)
Tyruko-sztn® (natalizumab-sztn)
Tofidence™ (tocilizumab-bavi)
APPROVED BIOSIMILARS continued
APPROVED BIOSIMILARS
Sandoz November 2019
Amgen December 2019
Pfizer June 2020
Mylan/Biocon June 2020
Mylan/Biocon July 2020
Amgen December 2020
Biogen September 2021
Eli Lilly December 2021
Coherus December 2021
Amneal March 2022
Amneal April 2022
Amneal May 2022
Coherus August 2022
Fresenius Kabi September 2022
Celltrion September 2022
Fresenius Kabi December 2022
Celltrion May 2023
Sandoz August 2023
Biogen/Bio-Thera Solutions September 2023
Originator (Manufacturer)
Neulasta (Amgen)
Remicade (Janssen)
Neulasta (Amgen)
Lantus® (Sanofi-Aventis)
Humira (Abbvie)
Rituxan (Genentech)
Lucentis® (Genentech)
Lantus (Sanofi)
Humira (Abbvie)
Neupogen (Amgen)
Avastin (Genentech)
Neulasta (Amgen)
Lucentis (Genentech)
Neulasta (Amgen)
Avastin (Genentech)
Humira (Abbvie)
Humira (Abbvie)
Tysabri® (Biogen)
Actemra® (Genentech)
* Abbvie’s adalimumab (Humira), adalimumab-adaz (Hyrimoz), and adalimumab-bwwd (Hadlima) are approved in 50 mg/mL (with citric acid/ citrate) and 100 mg/mL (citrate-free) concentrations. Adalimumab-aaty (Yuflyma) is only approved as a 100 mg/mL high concentration citrate-free formulation. All other biosimilars for Humira are approved as 50 mg/mL concentrations only.
† Pfizer’s Inflectra is marketed in the U.S.; Pfizer 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 U.S., 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.
BIOSIMILARS continued
The first biosimilar version of Abbvie’s adalimumab (Humira), adalimumab-atto (Amjevita) became available in the U.S. in January 2023. Several Humira biosimilars, including citrate-free and high-concentration formulations as well as an interchangeable product, launched in July 2023.
IMMUNOLOGY
adalimumab SC
Alvotech is seeking approval of their investigational biosimilar to Abbvie’s citrate-free, high-concentration (100 mg/ mL) Humira. Celltrion is seeking interchangeability for their FDA-approved adalimumab-aaty (Yuflyma) 100 mg/mL, a biosimilar to 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.
FDA APPROVAL TIMELINE
• Alvotech (AVT-02) – February 24, 2024
• Celltrion (Yuflyma) – October to December 2024 for interchangeability
FINANCIAL FORECAST (reported in millions) Year 2023 2024 2025 2026 2027
The forecast is a projection of total U.S. sales per year for the branded originator product
OPHTHALMOLOGY
intravitreal
Biocon/Janssen, Celltrion and Coherus are seeking approval of their investigational biosimilars 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
• Biocon/Janssen (MYL-1701) – Pending
• Celltrion (CT-P42) – June 28, 2024
• Coherus (FYB-203) – June 28, 2024
FINANCIAL FORECAST (reported in millions) Year 2023 2024 2025 2026 2027 Projected Total U.S.
The forecast is a projection of total U.S. sales per year for the branded originator product
BIOSIMILARS continued
ONCOLOGY bevacizumab IV
Bio-Thera Solutions/Sandoz and Centus 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/Sandoz (BAT1706) – Pending
• Centus (FKB238) – Pending
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $507 $432 $387 $348 $315
The forecast is a projection of total U.S. sales per year for the branded originator product
ENDOCRINE denosumab SC
Sandoz
Sandoz is seeking approval for their investigational biosimilar (GP2411) to Amgen’s receptor activator of nuclear factorkappa-B ligand (RANKL) inhibitor denosumab (Prolia®, Xgeva®). Prolia is indicated for the treatment of osteoporosis in men and postmenopausal women, treatment of glucocorticoid-induced osteoporosis in men and women, and to increase bone mass in women receiving adjuvant aromatase inhibitor therapy or men receiving androgen deprivation therapy; all indicated populations are high risk for fracture. Xgeva is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, treatment of select patients with giant cell tumor of bone, and treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
FDA APPROVAL TIMELINE
December 6, 2023
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $4,245 $4,441 $4,551 $3,895 $3,116
The forecast is a projection of total U.S. sales per year for the branded originator product
BIOSIMILARS continued
IMMUNOLOGY
eculizumab IV
Amgen
Amgen is seeking approval for their investigational biosimilar (Bekemv) to Alexion’s complement inhibitor eculizumab (Soliris®) that is indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).
FDA APPROVAL TIMELINE
February 2024
FINANCIAL FORECAST (reported in millions)
Projected Total U.S. Sales $1,708 $1,284 $968 $654 $483
The forecast is a projection of total U.S. sales per year for the branded originator product
BLOOD MODIFIER
filgrastim IV, SC
Apotex
Apotex is seeking approval of their investigational biosimilar (Grastofil) 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 who are acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome [HSARS]).
FDA APPROVAL TIMELINE
Pending
FINANCIAL FORECAST (reported in millions)
Projected Total U.S. Sales $45 $32 $25 $19 $15
The forecast is a projection of total U.S. sales per year for the branded originator product
BIOSIMILARS continued
ENDOCRINOLOGY
insulin aspart SC
Gan & Lee/Sandoz
Gan & Lee/Sandoz are seeking approval for their investigational biosimilar (GL-ASP) to Novo Nordisk’s rapid-acting human insulin analog insulin aspart (Novolog®) that is indicated to improve glycemic control in patients with diabetes mellitus.
FDA APPROVAL TIMELINE
April 14, 2023
FINANCIAL FORECAST (reported in millions)
The forecast is a projection of total U.S. sales per year for the branded originator product
ENDOCRINOLOGY
insulin glargine SC
Gan & Lee/Sandoz
Gan & Lee/Sandoz are seeking approval for their investigational biosimilar (Basalin) to Sanofi-Aventis’ long-acting human insulin analog insulin glargine (Lantus) that is indicated to improve glycemic control in patients with diabetes mellitus.
FDA APPROVAL TIMELINE
December 23, 2023
FINANCIAL FORECAST (reported in millions)
The forecast is a projection of total U.S. sales per year for the branded originator product.
BIOSIMILARS continued
ENDOCRINOLOGY
insulin lispro SC
Gan & Lee/Sandoz
Gan & Lee/Sandoz are seeking approval for their investigational biosimilar (Prandilin) to Eli Lilly’s rapid-acting human insulin analog insulin lispro (Humalog) that is indicated to improve glycemic control in patients with diabetes mellitus.
FDA APPROVAL TIMELINE
April 1, 2024
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales
The forecast is a projection of total U.S. 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, and Coherus is seeking approval for their investigational biosimilar to Amgen’s Neulasta Onpro®. Neulasta and Neulasta Onpro contain pegfilgrastim, 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
• Coherus (Udenyca OBI®) – October to December 2023
• Lupin (Lupifil-P) – Pending
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales Neulasta $622 $420 $347 $283 $234
Projected Total U.S. Sales Neulasta Onpro $2,972 $2,576 $2,390 $2,084 $1,833
The forecast is a projection of total U.S. sales per year for the branded originator product (Neulasta and Neulasta Onpro).
BIOSIMILARS continued
OPHTHALMOLOGY
ranibizumab intravitreal
Stada Arzneimittel/Xbrane
Stada Arzneimittel/Xbrane are seeking approval for their investigational biosimilar (Ximluci) to Genentech’s Lucentis, a vascular endothelial growth factor (VEGF) inhibitor indicated to treat wet age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME), diabetic retinopathy, and myopic choroidal neovascularization (mCNV).
FDA APPROVAL TIMELINE
April 21, 2024
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $665 $514 $408 $346 $321
The forecast is a projection of total U.S. sales per year for the branded originator product
IMMUNOLOGY/ONCOLOGY rituximab IV
Dr. Reddy’s
Dr. Reddy’s is seeking approval for their investigational biosimilar to Genentech’s Rituxan, a CD20-directed cytolytic antibody indicated for the treatment of select patients with non-Hodgkin’s lymphoma (NHL), mature B-cell NHL/mature B-cell acute leukemia, chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA), and pemphigus vulgaris.
FDA APPROVAL TIMELINE
May 10, 2024
FINANCIAL FORECAST (reported in millions)
Year 2023 2024 2025 2026 2027
Projected Total U.S. Sales $1,122 $914 $761 $679 $606
The forecast is a projection of total U.S. sales per year for the branded originator product.
BIOSIMILARS continued
IMMUNOLOGY
tocilizumab IV, SC
Fresenius Kabi
Fresenius Kabi is seeking approval for their investigational biosimilars to Genentech’s Actemra, an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of rheumatoid arthritis (RA), giant cell arteritis, systemic sclerosisassociated interstitial lung disease, polyarticular and systemic juvenile idiopathic arthritis (JIA), and cytokine release syndrome.
FDA APPROVAL TIMELINE
Pending
FINANCIAL FORECAST (reported in millions) Year 2023 2024 2025
Projected Total U.S. Sales $1,141 $895 $719 $604 $528
The forecast is a projection of total U.S. sales per year for the branded originator product
ONCOLOGY
trastuzumab IV
Henlius/Accord
Henlius/Accord are seeking approval of their investigational biosimilar (HLX02) 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 15, 2023
FINANCIAL FORECAST (reported in millions)
Projected Total U.S. Sales $360 $299 $261 $229 $197
The forecast is a projection of total U.S. sales per year for the branded originator product
Keep on Your RADAR
Notable agents that are further from approval have been identified in this unique watch list. These are products with the potential for significant clinical and financial impact. Their development status is being tracked on the MRx Pipeline radar. These pipeline products, their respective class or proposed indication, as well as an estimated financial forecast for the year 2027, are displayed. The financials are projected total annual US sales, reported in millions.
xanomeline-trospium
Behavioral health
$1,810
tovorafenib
Oncology
$374
tirzepatide
Weight management
$4,969
tabelecleucel
Oncology
$401
sotatercept
Cardiology
$1,453
reproxalap
Ophthalmology
$285
prademagene zamikeracel (EB-101)
Dermatology/Gene therapy
$129
insulin icodec
Endocrine
$318
aficamten
Cardiovascular $872 atidarsagene
autotemcel
Metabolic $89
blarcamesine
Neurology
$1,049
datopotamab deruxtecan
Oncology
$891
donanemab Neurology $1,261
fidanacogene elaparvovec
Hematology/Gene therapy
$193
giroctocogene fitelparvovec
Hematology/Gene therapy
influenza vaccine (FluMist® Quadrivalent)
(self-/caregiver-administered)
Infectious disease
$31
$106
Specialty drug names appear in magenta throughout the publication.
Pipeline DRUG LIST
The pipeline drug list is an aerial outline of drugs with anticipated FDA approval through 2024. It is not intended to be a comprehensive inventory of all drugs in the pipeline; emphasis is placed on drugs in high-impact categories. Investigational drugs with a Complete Response Letter (CRL).
3
APPLICATION SUBMITTED TO THE FDA IN PHASE 3 TRIALS
Specialty drug names appear in magenta throughout the publication.
PIPELINE DRUG LIST
Specialty drug names appear in magenta throughout the publication.
Submitted (New Drugs)
clobetasol propionate Salvat
capivasertib
AstraZeneca
donanemab
tirzepatide Eli Lilly
tislelizumab
Beigene/Novartis
chikungunya vaccine monovalent, live attenuated
taurolidine/heparin Cormedix
ocular pain and inflammation
Breast cancer (R/R, HR+/HER2-, locally advanced or metastatic, in combination with fulvestrant, prior endocrine-based therapy)
disease (early)
(plus weight-related comorbidities)
Esophageal squamous cell carcinoma (unresectable or metastatic, 2nd-line)
infection prevention
Reduction of catheterrelated bloodstream infections (CRBSIs) related to chronic hemodialysis
NSCLC (ROS1-positive, metastatic, previously treated with one ROS1 tyrosine kinase inhibitor and who have not received prior platinumbased chemotherapy)
(refractory, metastatic, ≥ 2nd-line)
trastuzumab (biosimilar to Genentech’s Herceptin) Henlius/Accord Breast cancer; Gastric or gastroesophageal junction adenocarcinoma
roflumilast foam
lovotibeglogene autotemcel
travoprost implant
insulin glargine (biosimilar to Sanofi-Aventis' Lantus)
von Willebrand factor/ coagulation factor VIII complex (lyophilized powder) (Wilate®) Octapharma
sotorasib (Lumakras®) Amgen
influenza vaccine, live (FluMist Quadrivalent)
Multiple myeloma (R/R, prior immunomodulatory, proteasome inhibitor, and anti-CD38 therapy)
Gastric and gastroesophageal junction adenocarcinoma (locally advanced unresectable or metastatic, 1st-line, in combination with fluoropyrimidine & platinum chemotherapy)
Immunoglobulin A (IgA) nephropathy (Berger’s disease)
(routine prophylaxis)
NSCLC (locally advanced or metastatic, KRAS G12Cmutated; ≥ 2-line)
