What Happened to the Potential Blockbusters Headed for Approval in 2020?

Back in February we identified eleven potential blockbusters on track for approval in 2020. At this point, five have been approved and six are in need of additional data from trials before the FDA will grant approval. The five approvals covered the following indications: migraine, relapsing multiple sclerosis (2 drugs), breast cancer, and spinal muscular atrophy. 
Read on to review the status of these eleven potential blockbusters:

1. Rimegepant from Biohaven Pharma (Nurtec ODT) -The FDA approved rimegepant on 2/27/2020 for the acute treatment of migraine with or without aura in adults. Rimegepant will compete with the triptans, ubrogepant and lasmiditan from Lilly. The gepants (ubrogepant and rimegepant) and lasmiditan do not cause vasoconstriction and may be an alternative when patients do not tolerate triptans. ICER reviewed lasmiditan, ubrogepant and rimegepant and found the drugs to be comparable in efficacy, but not as efficacious as triptans. Lasmiditan was found to have higher rates of dizziness and discontinuation. ICER concluded that lasmiditan, ubrogepant and rimegepant would provide a benefit for patients with cardiovascular disease that have a contraindication to triptans, were not helped by triptans or do not tolerate them.
2. Celgene’s ozanimod (Zeposia) - The FDA approved ozanimod on 3/25/2020 for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease. The outbreak of the COVID-19 pandemic delayed the launch of Zeposia. As of June 1, 2020, Zeposia is now available for prescription.
3. Immunomedics/Seattle Genetics’ sacituzumab govitecan (Trodelvy) - The FDA approved sacituzumab govitecan on 4/22/2020 to treat resistant metastatic triple-negative breast cancer. Trodelvy has a boxed warning about the potential risks for severe diarrhea and neutropenia.
4. The FDA approved risdiplam (Evrysdi) from Genentech/Roche on 8/7/2020, for treatment of spinal muscular atrophy (SMA) in adults and children 2 months of age and older. Risdiplam will be available through Accredo Health Group, an Express Scripts specialty pharmacy for direct delivery to patients’ homes. Risdiplam will compete with nusinersen (Spinraza, Biogen), which was approved in 2016. Risdiplam has weight and age based dosing until a child weighs 44 pounds. For patients that weigh 44 pounds or more, the dose is standardized to 5 mg per day. At 5 mg per day, Genentech has priced risdiplam at $340,000 per year. For an infant weighing 15 pounds, the annual cost would be less than $100,000. Both risdiplam and nusinersen increase production of survival motor neuron (SMN) protein. However, nusinersen is administered by intrathecal injection under anesthesia, while risdiplam is an oral liquid. WAC for nusinersen is $750,000 during the first year and $375,000 for each subsequent year.  Onasemnogene abeparvovec (Zolgensma, Novartis) is a single-dose gene therapy for SMA, but the drug has a price of over $2 million and a Black Box Warning regarding liver toxicity.
5. Ofatumumab from Novartis (Kesimpta) - The FDA approved ofatumumab (Kesimpta, Novartis) on 8/21/2020, for the treatment of adults with relapsing multiple sclerosis. Ofatumumab is administered monthly via an autoinjector pen. Novartis has set WAC at $83,000 per year. Ofatumumab has the same mechanism of action as ocrelizumab (Ocrevus, Roche), which is administered by intravenous infusion every six months and has an annual WAC of $65,000. Ofatumumab (Arzerra, Novartis) was approved as an intravenous infusion in 2009 for the treatment of chronic lymphocytic leukemia.
6. Vadadustat from Akebia Pharma/Mitsubishi Tanabe (no brand name available) – On 3 September 2020, Akebia Therapeutics announced top-line results from its PRO2TECT Global Phase 3 Program of Vadadustat for the treatment of Anemia due to chronic kidney disease in adult patients not on dialysis.
7. AbbVie dropped a partnership to develop Filgotinib with Galapagos and Gilead who continued on with development for Crohn's disease, rheumatoid arthritis, Ankylosing spondylitis. Although the EU approved the drug, the FDA rejected filgotinib due to concerns over toxicity with the 200 mg dose. The FDA requested data from the ongoing MANTA and MANTA-RAY trials, which are not expected to be completed until 2021. This would potentially delay resubmission of the filgotinib NDA until mid-2021.
8. Inclisiran, originally developed by a collaboration between Novartis, Alnylam Pharmaceuticals, and the Medicines Co., is in Phase III testing. The Medicines Company submitted an NDA for inclisiran to the FDA in December 2019. Novartis completed the purchase of The Medicines Company in January 2020. Inclusiran is administered as a subcutaneous injection. A second dose of inclusiran is administered 3 months after the first does as an initial loading dose regimen, then the drug is given every six months. Inclusiran lowers LDL by interfering with the RNA that leads to production of proprotein convertase subtilisin–kexin type 9 (PCSK9).
9. Lisocabtagene maraleucel is in Phase II development by Bristol-Myers Squibb, Juno Therapeutics, and Celgene. The FDA accepted the NDA for lisocabtagene maraleucel for the treatment of large B-cell lymphoma and set a PDUFA date for August 2020. The PDUFA date was then delayed by three months in May 2020 to allow the FDA time to review new requested data. The FDA has delayed approval of lisocabtagene maraleucel due to travel restrictions delaying the inspection of the manufacturing plant. A new PDUFA date has not been announced.
10. BioMarin Pharmaceutical’s valoctocogene roxaparvovec (Roctavian), to treat Hemophilia A, is in a Phase III trial expected to be concluded in November 2021, suggesting a 2021 resubmission of the valoctocogene roxaparvovec BLA. Previously, The FDA rejected valoctocogene roxaparvovec and said that at least two years of safety and efficacy data from the ongoing Phase III trial would be needed to support the sustainability of the reduced/eliminated Annualized Bleeding Rate. Three-year data from a Phase I/II trial suggested that factor VIII levels seemed to fall off after 12 to 18 months. This could potentially require additional doses to sustain efficacy, so the FDA would like additional data in a larger population.
11. AstraZeneca has marketing rights for roxadustat in the U.S. and China, while Astellas holds the rights in Japan, Europe and the Middle East. The drug is in various Phase III trials. The FDA accepted the NDA for roxadustat for the treatment of both dialysis-dependent and non-dialysis dependent anemia and a set a PDUFA date of 12/20/2020.