Clinical Alert 2022 September

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As of August 30, 2022, the CDC is tracking 18,417 confirmed monkeypox/orthopoxvirus cases across the US. There are also multiple clusters in more than 60 countries that do not usually report monkeypox. Monkeypox is spread through close skin-to-skin contact (e.g., sexual contact) or through contact with certain contaminated objects (e.g., linens). The CDC instructs HCPs to be on alert for rashes consistent with monkeypox that are firm or rubbery and well-defined with deepseated lesions. The rash may occur on the body, face, or genital area. A febrile prodrome may also occur that involves lymphadenopathy, headache, malaise, or chills. Monkeypox usually does not result in fatalities and resolves without treatment. Hospitalizations have occurred due to complications such as severe pain. Although there are currently no FDA-approved or FDA-authorized medications for treating monkeypox, tecovirimat (Tpoxx®) is an antiviral (orthopoxvirus VP37 envelope wrapping protein inhibitor) that is available through the CDC under the FDA’s Expanded Access Program. Tecovirimat was FDA-approved in 2018 as an oral capsule and IV solution indicated for a 14-day treatment course of smallpox in adults and pediatric patients weighing ≥ 3 kg. Currently, data do not exist demonstrating tecovirimat’s efficacy for monkeypox; therefore, conducting RCTs to determine safety and efficacy is important. The Modified Vaccinia Ankara (MVA) vaccine (Jynneos®) received FDA approval in 2019 for prevention of smallpox and monkeypox disease in those ≥ 18 years old who are at high risk for these infections as a SC injection in two doses (0.5 mL each) 4 weeks apart. Following the declaration of monkeypox as a Public Health Emergency, the FDA issued an EUA allowing intradermal administration of the vaccine for those ≥ 18 years old who are at high risk for monkeypox infection at one-fifth (0.1 mL) of the SC dose; two doses 4 weeks apart are still required. The 0.1 mL dose increases the number of available doses. The EUA also allows for SC use in those < 18 years old who are at high risk for monkeypox infection.

The FDA has also approved a citrate-free, highconcentration formulation of the biosimilar adalimumab-bwwd (Hadlima™) for the reference product adalimumab (Humira®). The high-concentration (100 mg/mL) formulation will be available in prefilled syringes and autoinjectors; the product was previously approved as a 50 mg/mL low-concentration formulation.

The FDA has authorized bivalent boosters for both the Pfizer/Biontech (≥ 12 years old) and Moderna (≥ 18 years old) COVID-19 vaccines. ACIP is meeting September 1st and 2nd to discuss the updated boosters that contain an Omicron BA.4/BA.5 strain. Previously, authorized for use only in adults, the EUA for the Novavax COVID-19 vaccine has been expanded to include individuals 12 to 17 years old, and the CDC has endorsed the vaccine as another primary series option for these individuals. Novavax has submitted for an EUA of its adjuvanted COVID-19 vaccine as a booster dose in adults. Please refer to the COVID-19 disclaimer at the end of the publication.

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The FDA has granted approval to the first interchangeable biosimilar to ranibizumab (Lucentis®): ranibizumab-eqrn (Cimerli™). Ranibizumab-eqrn is a VEGF inhibitor and approved for all five of the indications of the reference product. It is administered by intravitreal injection into the eye and will be supplied in an SDV in the strengths of 10 mg/mL (0.5 mg dose) or 6 mg/mL (0.3 mg dose). Interchangeable biosimilars have met additional requirements allowing for the biosimilar to be substituted at the pharmacy without the intervention of the prescriber, depending on state specific pharmacy substitution laws. Cimerli is expected to be available in early October 2022.



Approval of the new formulation was based on data from healthy subjects comparing the two formulations (100 mg/mL versus 50 mg/mL). Hadlima is expected to be available in July 2023.

• In response to the discovery of a nitrosamine impurity, Nitroso-STG-19 (NTTP), in samples of the T2DM drug sitagliptin (Januvia®), the FDA made an announcement that it will allow the temporary distribution of sitagliptin containing NTTP higher than the acceptable intake limit of 37 ng per day, up to 246.7 ng per day, to prevent a shortage.


• The FDA approved an on-body delivery system for SC administration of ravulizumab-cwvz (Ultomiris®) for paroxysmal nocturnal hemoglobinuria or atypical hemolytic uremic syndrome in adults. Ravulizumabcwvz was previously only approved for IV infusion for patients ≥ 1 month of age for the same indications and for the treatment of certain adults with generalized myasthenia gravis. The SC maintenance dosage is 490 mg once weekly in adults ≥ 40 kg using 2 of the 245 mg/3.5 mL on-body delivery systems (prefilled cartridge + on-body injector) which may be selfadministered.

• The FDA has published a webpage detailing the agency’s response to monkeypox.

• The CDC has issued an MMWR on interim guidance for prevention and treatment of monkeypox in persons with HIV infection.

• As of October 1, 2022, Teva will discontinue the manufacturing of ProAir® HFA (albuterol sulfate); Teva expects that there will be a 90-day supply available after the October 1st discontinuation date. An authorized generic of the ProAir HFA is available.


• The Institute for Clinical and Economic Review (ICER) has released the Final Evidence Report on betibeglogene autotemcel (beti-cel) (Zynteglo®) for the treatment of beta-thalassemia.

• The CDC has released an MMWR with interim recommendations of the ACIP on use of the Novavax COVID-19 vaccine in adults. The adjuvanted Novavax COVID-19 vaccine, given as a primary 2-dose series, is recommended as an additional option for unvaccinated adults.

• Acalabrutinib (Calquence®) tablets have received FDA-approval for the treatment of adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Accelerated Approval was also granted for this medication for the treatment of adults with mantle cell lymphoma (MCL) who have received ≥ 1 prior therapy. The 100 mg tablets are dosed at 100 mg orally every 12 hours. Acalabrutinib is also approved as 100 mg capsules with the same dosing for the same indications. Unlike the capsules, the tablet formulation does not have drug interactions with gastric acid-reducing agents.

• The North American Menopause Society (NAMS) has published the 2022 hormone therapy position statement

• The FDA granted full approval for capmatinib (Tabrecta®) for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) exon 14 skipping tumors. Accelerated Approval of this indication was granted in 2020 based on initial overall response demonstrated in the GEOMETRY mono-1 trial. Regular approval was based on an additional 63 patients and 22 months of follow-up evaluating response durability and clinical benefit. The recommended dose is 400 mg orally twice daily.


4 | SEPTEMBER 2022 PIPELINE NEWS UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES DRUG NAME MANUFACTURER THERAPEUTICFORMULATIONCLASS PROPOSED CLINICAL USE FDAANTICIPATEDAPPROVAL microbiota suspension Ferring • Rectal • Microbiota-based live biotherapeutic Clostridioides difficile infection (recurrent) September to November 2022 deucravacitinib Bristol-Myers Squibb • Oral • Tyrosine kinase 2 (TYK2) inhibitor Plaque (moderatepsoriasistosevere) 09/09/2022 eflapegrastim Spectrum • SC • Colony stimulating factor neutropeniaChemotherapy-induced 09/09/2022 linzagolix Obseva • Oral • hormoneGonadotropin-releasing(GnRH) antagonist Uterine fibroid-related heavy menstrual bleeding 09/13/2022 dasatinib Xspray • Oral • Tyrosine kinase inhibitor Chronic myeloid leukemia 09/16/2022 elivaldogene autotemcel Bluebird Bio • IV • Gene therapy Cerebral dystrophyadrenoleuko-(pediatrics) 09/16/2022 sodium thiosulfate Fennec • IV • Chelating agent ototoxicityChemotherapy-inducedprevention 09/23/2022 sodium tauroursodiolphenylbutyrate/ Amylyx • Oral • Nitrogen-binding agent/bile acid Amyotrophic lateral sclerosis 09/29/2022 bevacizumab (biosimilar to Genentech’s Avastin®) Celltrion • IV • VEGF inhibitor Brain cancer; cervical cancer; colorectal cancer; non-small cell lung cancer; ovarian cancer; renal cell carcinoma 09/30/2022 futibatinib Otsuka • Oral • Fibroblast growth factor receptor (FGFR) inhibitor Cholangiocarcinoma (locally advanced or metastatic, prior treatment, FGFR2 gene rearrangements) 09/30/2022

• Extended-release oral tablet: 45 mg/105 mg

DRUG MANUFACTURERNAME NewDESCRIPTIONDrugs Arcutisroflumilast(Zoryve™)Biotherapeutics • NDA approval 07/29/2022; Standard Review • Indicated for the topical treatment of plaque psoriasis, including intertriginous areas, in patients ≥ 12 years of age • Phosphodiesterase-4 inhibitor • Topical cream: 0.3% in a 60 g tube • Recommended dosage is 1 application to affected areas of skin once daily, rubbing in completely; wash hands following application, unless intended treatment site is the hands betibeglogene autotem cel(Zynteglo(beti-cel) ®) Bluebird Bio • BLA approval 08/17/2022; Breakthrough Therapy, Fast Track, Orphan Drug, Priority Review, Rare Pediatric Disease Designation • Indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions • Autologous hematopoietic stem cell-based gene therapy • Cell suspension: 5 × 106 CD34+ cells/kg of body weight in ≥ 1 infusion bags; patients undergo hematopoietic stem cell mobilization followed by apheresis to obtain CD34+ cells for manufacturing • Minimum recommended dosage is 5 × 106 CD34+ cells/kg (autologous use only) given as a one-time, single-dose IV infusion over < 30 minutes with full myeloablative conditioning before the infusion; prophylaxis for hepatic venoocclusive disease should be given and prophylaxis for seizures should be considered • Product will be available only at Qualified Treatment Centers dextromethorphan hyd robromide/hydrochloridebupropion(Auvelity™)Axsome

• Indicated for the treatment of major depressive disorder in adults

• Combination of dextromethorphan, an uncompetitive N-methyl D-aspartate (NDMA) receptor antagonist and sigma-1 receptor agonist, and bupropion, an aminoketone and cytochrome P450 (CYP) 2D6 inhibitor

• Recommended initial dosage is 1 tablet once daily in the morning; after 3 days, increase to a maximum of 1 tablet twice daily (separated by ≥ 8 hours); monitor blood pressure before and during therapy Boxed warning for suicidal thoughts and behaviors Product availability is expected in 4Q 2022 = FDA approval pathway that allows for submission of data from studies not conducted by or for the applicant.

• 505(b)(2) NDA approval 08/18/2022; Breakthrough Therapy, Priority Review



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ACIPGlossary: National Institutes of Health RCT randomized controlled trial RPh registered pharmacist SC subcutaneous SDV single-dose vial T2DM type 2 diabetes mellitus US United States VEGF vascular endothelial growth factor WHO World Health Organization References:

COVID-19 Disclaimer: For more resources on COVID-19, visit the Magellan Rx Coronavirus Update webpage. For the most current information, visit the FDA, CDC, NIH, NIH guidelines, and WHO websites. State and local health departments also provide valuable information regarding management in local communities. As the COVID-19 landscape is fluid, assumptions are subject to change.

Advisory Committee on Immunization Practices BLA Biologics License Application CDC Centers for Disease Control and Prevention COVID-19 Coronavirus Disease 2019 EUA Emergency Use Authorization FDA Food and Drug Administration g gram HCP healthcare professional HIV human immunodeficiency virus IV intravenous MMWR Morbidity and Mortality Weekly Report NDA New Drug Application NIH

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