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Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.
FDA approval rate speeds up despite COVID-19 complications.
Despite the COVID-19 pandemic, FDA’s approval rate in 2020 remained high. As of Dec. 17, 2020, 50 new drugs had been approved by the agency’s Center for Drug Evaluation and Research (CDER) (1), surpassing the 48 new drugs approved in all of 2019 (2). An additional 65 first-time generics were granted marketing authorization in 2020 (3). As the year wound to a close, six small-molecule and two biologic drug applications had Prescription Drug User Fee Act (PDUFA) decision dates scheduled before the end of 2020 (4), creating the potential for 58 approvals, which would be comparable to 2018 (5).
A few interesting firsts and trends are highlighted in the following.
One of the most exciting approvals went to Gilead Sciences for its new treatment for patients with COVID-19 requiring hospitalization (6). Veklury (remdesivir) originally was granted Emergency Use Authorization (EUA) in May 2020. Unlike the EUA, the approval does not include pediatric patients weighing less than 40 kg. The drug received accelerated approval under FDA’s Coronavirus Treatment Acceleration Program. Remdesivir was also granted fast track and priority review designations and a material threat medical countermeasure priority review voucher.
COVID-19 wasn’t the only disease for which first therapies were approved. In fact, many of the drugs granted marketing authorization by FDA in 2020 are first treatments. In May, FDA approved the first drug for treatment of severe malaria (7). Amivas’ artesunate for injection was previously only available to patients through FDA’s expanded access program. Artesunate received priority review and orphan drug designation.
Tepezza (teprotumumab-trbw) is an antibody drug conjugate (ADC) from Horizon Therapeutics Ireland DAC for the treatment of thyroid eye disease that can potentially spare patients from multiple invasive surgeries (8). It was granted priority review, fast track, and breakthrough therapy designations and supported in part by the FDA Orphan Products Grants Program.
Ultragenyx Pharmaceutical and Alnylam Pharmaceuticals both received approvals for first treatments for two metabolic disorders: Dojolvi (triheptanoin), a highly purified, synthetic, seven-carbon fatty acid triglyceride as a source of calories and fatty acids, for the treatment of pediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (9) and Oxlumo (lumasiran) for the rare genetic disorder, primary hyperoxaluria type 1 (PH1) (10), respectively. Effort to achieve the latter approval was coordinated by the Oxalosis & Hyperoxaluria Foundation and the Kidney Health Initiative.
FDA also approved Zokinvy (lonafarnib, Eiger Biopharmaceuticals) as the first treatment to reduce the risk of death due to Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in patients one year of age and older (11).
Several first therapies approved in 2020 are targeted against very specific diseases, and many fall into the class of drugs known as kinase inhibitors. Examples include Ayvakit (avapritinib, Blueprint Medicines Corporation) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation (12); Koselugo (selumetinib, AstraZeneca Pharmaceuticals), the first treatment of neurofibromatosis type 1 (NF1), a genetic disorder of the nervous system causing tumors to grow on nerves (13); Pemazyre (pemigatinib, Incyte Corporation), the first treatment approved for adults with certain types of previously treated, advanced bile duct cancer (cholangiocarcinoma) (14); Tabrecta (capmatinib, Novartis) for the treatment of adult patients with non-small cell lung cancer (NSCLC) that has spread to other parts of the body and whose tumors have mutations that lead to MET exon 14 skipping (15); and Retevmo (selpercatinib, Loxo Oncology, Inc., a subsidiary of Eli Lilly and Company) for the treatment of three types of tumors with alterations of the “rearranged during transfection” gene (16).
Three drugs with notable mechanisms of action were approved by FDA in 2020. Rukobia (fostemsavir, ViiV Healthcare) is a new type of anti-retroviral medication for adults living with human immunodeficiency virus (HIV) who have tried multiple HIV medications and whose HIV infection cannot be successfully treated with other therapies because of resistance, intolerance, or safety considerations (17). Rukobia received fast track, priority review, and breakthrough therapy designations. Winlevi (clascoterone cream 1%, Cassiopea) for the treatment of acne in patients 12 years and older is the first acne drug with a new mechanism of action to receive approval in nearly 40 years (18). It operates via a non-antibiotic approach, targeting androgen receptors directly in the skin.
Blenrep (belantamab mafodotin-blmf) is a first-in-class anti-B-cell maturation antigen therapy for patients whose disease has progressed despite prior treatment with an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody (19). It is one of five drugs from GlaxoSmithKline approved by FDA in 2020 and one of 10 ADCs receiving agency approval (1). Blenrep comprises a humanized B-cell maturation antigen (BCMA) monoclonal antibody (mAb) conjugated to the cytotoxic agent, auristatin F, via a non-cleavable linker. The drug linker technology is licensed from Seattle Genetics; the mAb is produced using POTELLIGENT Technology licensed from BioWa.
Tauvid (flortaucipir F18, Avid Radiopharmaceuticals) is the first drug designed to help image tau pathology (20). It is used with positron emission tomography of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles, a primary marker of Alzheimer’s disease.
In July, Kite, part of Gilead, became the first company with multiple chimeric antigen receptor (CAR) T-cell therapy approvals (21). Tecartus (brexucabtagene autoleucel) is the first approved CAR T-cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, a rare form of non-Hodgkin lymphoma. The autologous anti-CD19 CAR T-cell therapy uses the XLP manufacturing process, which includes T-cell enrichment, a necessary step in certain B-cell malignancies in which circulating lymphoblasts are a common feature.
Several new drugs approved by FDA in 2020 address both the disease in question and patient needs for ease and/or convenience. Vyepti (eptinezumab-jjmr, Lundbeck) was approved as the first intravenous preventive treatment for migraine (22). The therapy allows many patients to experience relief within days and then over a period of several months. This ADC binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. Biohaven Pharma’s Nurtec ODT (rimegepant) is another CGRP receptor antagonist for treatment of migraine, but the only one available in a fast-acting orally disintegrating tablet (ODT) (23). According to the company, a single oral dose of Nurtec ODT 75 mg can provide fast pain relief and return patients to normal function within one hour, with many also experiencing sustained relief for up to 48 hours
Inqovi (decitabine and cedazuridine) tablets from Astex Pharmaceuticals, a subsidiary of Otsuka Pharmaceutical, is a treatment for myelodysplastic syndromes and chronic myelomonocytic leukemia that can be taken at home (24). Previous intravenous therapies required a visit to a healthcare facility. Evrysdi (risdiplam, Genentech) for the treatment of spinal muscular atrophy is also an oral therapy and the first for this disease (25).
International collaboration was emphasized by FDA in 2020. Two drugs were approved as part of Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE) that provides a framework for concurrent submission and review of oncology products among international partners (26). Collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval, according to the agency. With a framework for concurrent submission and review of oncology drugs, Project Orbis also facilitates a collaborative review to identify any regulatory divergence across review teams.
The kinase inhibitor Tukysa (tucatinib, Seattle Genetics) was approved in combination with chemotherapy (trastuzumab and capecitabine) for the treatment of adult patients with advanced forms of HER2-positive breast cancer that can’t be removed with surgery or has spread to other parts of the body (27). FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore), and Swissmedic (SMC, Switzerland) on the review—the first time the agency worked with HSA and Swissmedic. Tukysa was also reviewed using the real-time oncology review (RTOR) pilot program to streamline data submission and the assessment aid to facilitate discussions among the regulatory agencies and regulatory review. The drug received priority review, breakthrough therapy, fast track, and orphan drug designations.
Qinlock (ripretinib, Deciphera Pharmaceuticals), another kinase inhibitor, is the first new drug specifically approved by FDA as a fourth-line treatment for advanced gastrointestinal stromal tumor (28). FDA collaborated with TGA and Health Canada on the review of this application as part of Project Orbis. Qinlock received the same four designations as Tukysa, and the RTOR and assessment aid were used for its review.
Finally, FDA granted approval to the first treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients to Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn), a combination of three mAbs from Regeneron Pharmaceuticals (29). The data used to evaluate Inmazeb were collected from a clinical trial and through an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018–2019. FDA stated in its press release about the approval that international collaboration was key to achieving success in the fight against Ebola virus.
1. FDA, “Novel Drug Approvals for 2020,” www.fda.gov, accessed Nov. 27, 2020.
2. FDA, “Novel Drug Approvals for 2019,” www.fda.gov, accessed Nov. 27, 2020.
3. FDA, “First Generic Drug Approvals,” www.fda.gov, accessed Nov. 27, 2020.
4. RTT News, “FDA Calendar,” www.rttnews.com, accessed Nov. 27, 2020.
5. FDA, “Novel Drug Approvals for 2018,” www.fda.gov, accessed Nov. 27, 2020.
6. FDA, “FDA Approves First Treatment for COVID-19,” Press Release, Oct. 22, 2020.
7. FDA, “FDA Approves Only Drug in U.S. to Treat Severe Malaria,” Press Release, May 26, 2020.
8. FDA, “FDA approves first treatment for thyroid eye disease,” Press Release, Jan. 21, 2020.
9. Ultragenyx, “Ultragenyx Announces U.S. FDA Approval of, the First FDA-Approved Therapy for the Treatment of Long-chain Fatty Acid Oxidation Disorders,” Press Release, June 30, 2020.
10. FDA, “FDA Approves First Drug to Treat Rare Metabolic Disorder,” Press Release, Nov. 23, 2020.
11. FDA, “FDA Approves First Treatment for Hutchinson-Gilford Progeria Syndrome and Some Progeroid Laminopathies,” Press Release, Nov. 20, 2020.
12. FDA, “FDA approves the first targeted therapy to treat a rare mutation in patients with gastrointestinal stromal tumors,” Press Release, Jan. 9, 2020.
13. FDA, “FDA Approves First Therapy for Children with Debilitating and Disfiguring Rare Disease,” Press Release, April 10, 2020.
14. FDA, “FDA Approves First Targeted Treatment for Patients with Cholangiocarcinoma, a Cancer of Bile Ducts,” Press Release, April 17, 2020.
15. FDA, “FDA Approves First Targeted Therapy to Treat Aggressive Form of Lung Cancer,” Press Release, May 6, 2020.
16. FDA, “FDA Approves First Therapy for Patients with Lung and Thyroid Cancers with a Certain Genetic Mutation or Fusion,” Press Release, May 8, 2020.
17. FDA, “FDA Approves New HIV Treatment for Patients with Limited Treatment Options,” Press Release, July 2, 2020.
18. Cassiopea, “Cassiopea Receives FDA Approval for Winlevi (clascoterone cream 1%), First-in-Class Topical Acne Treatment Targeting the Androgen Receptor,” Press Release, Aug. 27, 2020.
19. GSK, “FDA Approves GSK’s BLENREP (belantamab mafodotin-blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma,” Press Release, August 6, 2020.
20. FDA, “FDA Approves First Drug to Image Tau Pathology in Patients Being Evaluated for Alzheimer’s Disease,” Press Release, May 28, 2020.
21. Gilead, “U.S. FDA Approves Kite’s Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma,” Press Release, July 24, 2020.
22. Lundbeck, “FDA approves Lundbeck’s Vyepti (eptinezumab-jjmr)—the First and Only Intravenous Preventive Treatment for Migraine,” Press Release, February 22, 2020.
23. Biohaven Pharma, “Biohaven’s NURTEC ODT (rimegepant) Receives FDA Approval for the Acute Treatment of Migraine in Adults,” Press Release, February 27, 2020.
24. FDA, “FDA Approves New Therapy for Myelodysplastic Syndromes (MDS) That Can be Taken at Home,” Press Release, July 7, 2020.
25. FDA, “FDA Approves Oral Treatment for Spinal Muscular Atrophy,” Press Release, August 7, 2020.
26. FDA, “Project Orbis,” www.fda.gov, accessed Nov. 27, 2020.
27. FDA, “FDA Approves First New Drug Under International Collaboration, a Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer,” Press Release, April 17, 2020.
28. FDA, “FDA Approves First Drug for Fourth-Line Treatment of Advanced Gastrointestinal Stromal Tumors,” Press Release, May 15, 2020.
29. FDA, “FDA Approves First Treatment for Ebola Virus,” Press Release, October 14, 2020.
Cynthia Challener, PhD, is a contributing editor to Pharmaceutical Technology.
Vol. 45, No. 1
When referring to this article, please cite it as C. Challener, “FDA Ends 2020 with High Drug Approval Rate,” Pharmaceutical Technology 45 (1) 2021.