March 7, 2023 PAO-03-23-NI-03
After three years of high drug approval numbers (48 in 2019, 53 in 2020,2 and 503 in 2021), the U.S. Food and Drug Administration (FDA) through its Center for Drug Evaluation and Research (CDER) gave marketing authorization to just 374 new drugs in 2022, the lowest since just 30 drugs were approved in 2016 and lower than the 10-year average of 485 and an average of 51 per year since 2017.6
Several different reasons have been enumerated for the 40% decline in approvals compared with 2021.5–7 A major factor could be the significant staff shortages at the FDA. The agency also has a new commissioner. Continued limited travel and thus limited ability for the agency to conduct onsite audits and inspections due to the ongoing COVID-19 pandemic may be another. The backlash from the problematic approval of the Alzheimer drug Aduhelm, which has resulted in the tightening of approval standards, is a possible third contributor. It has been suggested that a greater number of complete response letters are being issued by the FDA. A decline in new drug applications is thought to be unlikely. However, a simple cyclical blip certainly cannot be ruled out.
The reduction in approvals is having an impact on the pharma market, largely in the delay of expected drug launches. Those delays are not only impacting company financials, they are also resulting in delays of major deals.7
One of the most notable developments in 2022 is the fact that, of the 37 new drugs approved by CDER, 15 were biologics (excluding gene and cell therapies and new indications for previously approved drugs) — 40.5%, a significant jump from the 28.0% in 2021 and far above the highest previously level of 31.8% in 2016.8
Seven new biosimilars were approved in 2022, including two interchangeable biosimilars — biosimilars that can be substituted by pharmacists without intervention by prescribers, subject to specific state laws.4 The approvals included biosimilars for the cancer drug Avastin (two separate approvals), the eye treatment Lucentis, the anti-infective Neulasta (two separate approvals), the anti-inflammatory Humira, and Neupogen, which prevents complications from chemotherapy.
Overall, CDER has approved a total of 40 biosimilars for 11 different reference products since 2015, including eight biosimilars to Humira; six biosimilars to Neulasta; five biosimilars to Herceptin; four biosimilars to Remicade and Avastin; three biosimilars to Rituxan and Neupogen; two biosimilars to Lantus, Enbrel, and Lucentis; and one biosimilar to Epogen/Procit.4 There are now also four approved interchangeable biosimilars.
Given the strong emphasis of most big pharma and many emerging/small pharma companies on the development of immuno-oncology and other cancer therapies, it is not surprising that the class of drugs receiving the most FDA approval in 2022 targeted various cancers. Of the 37 drugs approved, 11 were oncology drugs.8 The next largest group (7) receiving FDA approvals in 2022 were developed to treat autoimmune diseases. Four different therapies were approved to treat infectious diseases and another four to treat central nervous system disorders. Two approved products target eye diseases and one is a cardiovascular treatment. The remaining eight approved products are uncategorized.
Another continuing trend in 2022 was the high percentage of approved therapies leveraging various special designations issued by the agency with the goal of reducing approval times for truly novel candidates. Several drugs received Accelerated Approval (6, 16%), Breakthrough Therapy (13, 35%), Fast Track (12, 32%), and Priority Review (21, 57%).4 Overall, 24 (65%) of the novel drugs approved in 2022 used one or more of the FDA’s four expedited program.
It is also worth noting that 28 (76%) of the 37 drugs approved by CDER in 2022 were approved on the first review cycle, and 25 (68%) received their first approval in the United States (vs. in another country).4
The shift in focus from development of blockbusters to the development of drugs to treat rare diseases remained evident in 2022, with 20 (54%) of the 37 new drug approvals targeting such disorders.4 Diseases for which there are now approved treatments include polyneuropathy, amyotrophic lateral sclerosis (ALS), hemolytic anemia, cyclin-dependent kinase-like 5 deficiency disorder (CDD), hepatorenal syndrome, cold agglutinin disease acid sphingomyelinase deficiency (Niemann-Pick disease type A, B, A/B), generalized pustular psoriasis, intermediate or high-risk primary or secondary myelofibrosis, obstructive hypertrophic cardiomyopathy, metastatic or unresectable uveal melanoma, relapsed and refractory multiple myeloma, unresectable hepatocellular carcinoma, relapsed or refractory follicular lymphoma, and recurrent ovarian cancer that is resistant to platinum therapy.
Of the 37 drugs approved in 2022 by FDA, 20 (54%) are considered to be first-in-class therapies, or drugs with novel mechanisms of action.4 Examples include a new cardiovascular treatment for obstructive hypertrophic cardiomyopathy (Camzyos, mavacamten), a new treatment for type 2 diabetes that activates two hormone receptors for improved glycemic control (Mounjaro, tirzepatide), a radiopharmaceutical to treat prostate cancer (Pluvicto, lutetium 177 Lu vipivotide tetraxetan), and new therapies to treat HIV (Sunlenca, lenacapavir) and type 1 diabetes (Tzield, teplizumab-mzwv).
Next-generation biologic drugs including cell and gene therapies, as well as vaccines, are evaluated and approved by the FDA’s Center for Biologics Evaluation and Research (CBER). In 2022, CBER approved two gene therapies and three cell therapies, as well as Pfizer’s Spikevax mRNA vaccine against COVID-19 and a new live vaccine against measles, mumps, and rubella (Priorix, GlaxoSmithKline).9 A live biotherapeutic (Rebyota, Ferring Pharmaceuticals) in the form of fecal microbiota for the prevention of recurrence of Clostridioides difficile infection (CDI) also received FDA approval in 2022.
The two gene therapies include Adstildadrin (nadofaragene firadenovec, Ferring Pharmaceuticals) for the treatment of adults with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors10 and Hemgenix (etranacogene dezaparvovec-drlb, CSL Behring) for the treatment of adults with hemophilia B (congenital Factor IX deficiency) who currently use Factor IX prophylaxis therapy or have current or historical life-threatening hemorrhage or repeated, serious spontaneous bleeding episodes.11
Two of the three gene-modified cell therapy approvals went to bluebird bio: Skysona (elivaldogene autotemcel) to slow the progression of neurologic dysfunction in boys 4–17 years of age with early, active cerebral adrenoleukodystrophy (CALD)12 and Zynteglo (betibeglogene autotemcel) for the treatment of adult and pediatric patients with ß-thalassemia who require regular red blood cell (RBC) transfusions.13 Janssen Biotech received the third approval for a gene-modified cell therapy for its product Carvykti (ciltacabtagene autoleucel), which targets adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy.14
Dr. Challener is an established industry editor and technical writing expert in the areas of chemistry and pharmaceuticals. She writes for various corporations and associations, as well as marketing agencies and research organizations, including That’s Nice and Nice Insight.