March 2021 decisions expected from the FDA

At Prime Therapeutics (Prime), we’ve positioned ourselves to best prepare our clients to manage new drugs. Our clinical and trade relations teams keep a keen eye on drugs likely to be approved by the U.S. Food and Drug Administration (FDA).

3/1/2021: Stimufend® (MSB11455 (biosimilar pegfilgrastim))

The FDA is reviewing Fresenius Kabi’s Stimufend, a biosimilar version of Amgen’s long-acting granulocyte-colony stimulating factor (G-CSF) Neulasta®. Stimufend is applying for approval based on two clinical trials that demonstrated equivalent pharmacokinetic and pharmacodynamic profiles to pegfilgrastim.1 Currently there are three other pegfilgrastim biosimilars that have launched: Ziextenzo®, Udenyca®, and Fulphila®.

3/1/2021: ropeginterferon alfa-2b

PharmaEssentia’s ropeginterferon alfa-2b is being evaluated by the FDA for patients with polycythemia vera (PV) in the absence of symptomatic splenomegaly. Ropeginterferon alfa-2b is a long-acting mono-pegylated proline interferon that is designed to increase convenience and has pharmacokinetic properties compared to conventional interferons. It is administered once every two weeks or once every four weeks during long-term maintenance. Ropeginterferon alfa-2b is seeking approval based on the Phase 3 PROUD/CONTI-PV trial in which patients with PV were treated with either ropeginterferon alfa-2b or hydroxyurea. At 36 months, the complete hematological response rate was much higher in the ropeginterferon alfa-2b group compared to the patients receiving hydroxyurea (70.5% versus 51.4% respectively). Additionally, 66% of patients treated with ropeginterferon alfa-2b reached a molecular response compared with 27% of patients treated with hydroxyurea.2

3/2/2021: KP415

KemPharm’s KP415 is seeking approval from the FDA for treatment of attention deficit hyperactivity disorder (ADHD). KP415 is an oral film that co-formulates Kempharm’s prodrug of d-methylphenidate (d-MPH), utilizing both an extended release and controlled release. KemPharm claims KP415 is designed to decrease abuse potential in patients with ADHD by demonstrating a significantly lower maximal drug, compared with other methylphenidate products. It is also only converted to the active dexmethylphenidate form when taken orally, therefore it prevents abuse risk via injection or snorting routes.3 Despite KemPharma’s claim that KP415 can be dosed once daily due to a duration of effect of 13 hours, clinical trials have not supported this claim. KP415 is applying for approval through the 505(b)(2) pathway using Akermes’ Focalin® (dexmethylphenidate) as its reference product. Similar products include methylphenidate and its generics.

1Q2021: FYB201 (ranibizumab biosimilar)

The FDA is reviewing Coherus Biosciences’ FYB201 as a biosimilar of Roche’s Lucentis® (ranibizumab) for wet age-related macular degeneration, macular edema following retinal vein occlusion, and diabetic macular edema. FYB201 is seeking approval based on clinical trials that met its primary endpoint by demonstrated comparability with Lucentis in terms of safety, efficacy and immunogenicity.4 If approved, FYB201 could be the first approved biosimilar for Lucentis.

3/18/2021: ponesimod

Janssen’s ponesimod is being reviewed by the FDA for treatment of relapsing multiple sclerosis. Ponesimod is a selective sphingosine-1-phosphate receptor 1 immunomodulator. Ponesimod is seeking approval based on the Phase 3 study OPTIMUM, which demonstrated ponesimod 20mg had a statistically significant reduction of 30.5% annualized relapse rate (ARR) compared to Sanofi Genzyme’s Aubagio® (teriflunomide) (0.202 relapses per year for ponesimod versus 0.290 for Aubagio).5 Ponesimod treatment compared with Aubagio also significantly reduced (by 56%) the average number of new, active, inflammatory brain lesions visible on magnetic resonance imaging (MRI). Additionally, investigators found that patients treated with ponesimod had fatigue symptoms that stabilized with treatment while patients treated with Aubagio had worsening fatigue over time. Similar products include Novartis’ Gilenya® (fingolimod), Novartis’ Mayzent® (siponimod), and Bristol Myers Squibb’s Zeposia® (ozanimod).

3/20/2021: roxadustat

The FDA is reviewing FibroGen Inc. and AstraZeneca’s roxadustat to treat anemia of chronic kidney disease (CKD) in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin improving iron regulation and reducing hepcidin. In DD patients, Phase 3 analyses showed roxadustat triggered a significantly higher increase in hemoglobin levels compared with Epogen/Procrit, with mean change from baseline averaged over weeks 28 to 52 standing at hemoglobin (Hb) levels of 1.22 g/dL and 0.99 g/dL respectively.6 In NDD patients, roxadustat was superior to placebo with a mean increase from baseline in Hb levels averaged over weeks 28-52 of 1.85 g/dL in patients treated with roxadustat compared to 0.13 g/dL with placebo. The FDA postponed its decision deadline to March 20, 2021 from December 20, 2020 in order to further clarify analyses of clinical data. Similar products include Amgen’s Aranesp® (darbepoetin alfa) and Roche’s Mircera® (methoxy polyethylene glycol-epoetin beta).

3/21/2021: fosdenopterin (BBP-870)

Origin Biosciences’ fosdenopterin is being reviewed by the FDA as a synthetic cyclic pyranopterin monophosphate (cPMP) for treatment of molybdenum cofactor deficiency (MoCD) Type A. MoCD Type A results in severe and irreversible neurological injury with a median survival between three to four years.7 Fosdenopterin is a first-in-class medication that must be administered intravenously (IV) daily. Fosdenopterin’s submission is supported by two ongoing trials in a rolling review process that have not been published publicly. There are currently no FDA-approved products for MoCD.

3/27/2021: Zegalogue™ (dasiglucagon) HypoPal® Rescue Pen

Zealand Pharma’s Zegalogue HypoPal Rescue Pen is seeking approval from the FDA as a glucagon analog, stable in liquid formulation as a ready-to-use pen injector for treatment of severe hypoglycemia in patients with diabetes. Zegalogue was tested in both adults and pediatrics in three Phase 3 clinical trials. Zegalogue met the primary and all key secondary endpoints, demonstrating a median time to blood glucose recovery of 10 minutes. This compared to 40 minutes with placebo and 12 minutes with GlucaGen.8 Zegalogue was not more effective than rival Novo Nordisk’s GlucaGen®. Ninety-two percent of subjects ages 12 to 17 were nauseous after taking Zegalogue, compared to 17% of those who took GlucaGen, with two-thirds of that Zegalogue age group vomiting.8 Similar products include glucagon Lilly’s Baqsimi® (glucagon injection), and Xeris Pharmaceuticals’ Gvoke® (glucagon injection).

3/27/2021: idecabtagene vicleucel (bb2121, ide-cel)

The FDA has granted priority review for Bristol-Myers Squibb and Bluebird Bio’s idecabtagene vicleucel for treatment of adults with multiple myeloma (MM) who have received at least three prior therapies, including an immunomodulator, a proteasome inhibitor and an anti-CD38 antibody. Idecabtagene vicleucel demonstrated a 73% overall response rate (ORR) and 33% complete response rate (CRR). The median progression-free survival (PFS) was 8.6 months.9 Similar products include Kite’s Yescarta® (axicabtagene ciloleucel), Novartis’ Kymriah® (tisagenlecleucel), but idecabtagene vicleucel would be the first chimeric antigen receptor T cells (CAR-T) for MM.

3/31/2021: tivozanib

Aveo Oncology’s tivozanib is being reviewed by the FDA for treatment of relapsed or refractory renal cell carcinoma (RCC). Tivozanib is an oral, once-daily next-generation vascular endothelial growth factor tyrosine kinase inhibitor. Tivozanib is seeking approval based on the Phase 2 TVIO-3 that demonstrated superiority over Bayer’s Nexavar® (sorafenib) as treatment of refractory metastatic RCC. The median overall survival (OS) in the tivozanib arm was 16.4 months and 19.2 months in the sorafenib arm. Tivozanib also led to an ORR of 34% compared with 24% for sorafenib.10 Responses were partial responses, which occurred in 80% of patients in the tivozanib arm versus only 8% of those in the sorafenib arm. Similar products include Novartis’ Votrient® (pazopanib) and Pfizer’s Sutent® (sunitinib malate).

While the information in this newsletter is from sources we believe to be reliable, we do not warrant that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to make assumptions about formulary status. Each trademarked drug name is the property of its respective owner.

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References

1. https://www.fresenius-kabi.com/news/regulatory-submission-for-pegfilgrastim-biosimilar-accepted-for-review-by-FDA

2. https://www.ashclinicalnews.org/news/literature-scan/ropeginterferon-alfa-2b-leads-durable-responses-hydroxyurea-pv/

3. https://www.globenewswire.com/news-release/2020/05/04/2026679/0/en/NDA-Filing-for-Potential-New-ADHD-Treatment-KP415-Accepted-by-FDA-KemPharm-Eligible-to-Receive-5-Million-Milestone-Payment-from-Gurnet-Point-Capital.html

4. https://www.formycon.com/en/biosimilars/fyb201/

5. https://www.fiercebiotech.com/biotech/janssen-sends-off-nda-for-new-multiple-sclerosis-drug-ponesimod

6. https://www.fiercepharma.com/pharma/az-fibrogen-s-roxadustat-decision-delayed-by-fda-but-approval-still-likely-analysts

7. https://bridgebio.com/news/bridgebio-pharma-and-affiliate-origin-biosciences-announces-fda-acceptance-of-its-new-drug-application-for-fosdenopterin-for-the-treatment-of-mocd-type-a

8. https://www.zealandpharma.com/dasiglucagon-rescue

9. https://news.bms.com/news/details/2020/U.S.-Food-and-Drug-Administration-FDA-Accepts-for-Priority-Review-Bristol-Myers-Squibb-and-bluebird-bio-Application-for-Anti-BCMA-CAR-T-Cell-Therapy-Idecabtagene-Vicleucel-Ide-cel-bb2121/default.aspx

10. https://www.targetedonc.com/view/fda-accepts-nda-for-tivozanib-in-relapsed-refractory-renal-cell-carcinoma