FDA’s Novel Approvals Again Led By Oncology And Neurology, But Dermatology Also Shone In 2022
Executive Summary
Pink Sheet infographic breaks down the trends and surprises in 2022 approvals. Cancer therapies and non-malignant hematology exceeded the average use of expedited review programs but were weighted to orphan diseases, while dermatology saw first-in-class approvals for big markets.
Dermatology joined neurology and oncology as the drivers of the US FDA’s novel drug and biologic approvals in 2022, riding a wave of immunomodulation therapies that parallel the continuing rise of immuno-oncology.
Cancer therapies were, reliably, the biggest group of novel approvals by the FDA’s drug and biologic review centers. While the number of novel cancer treatments was lower in 2022 than in 2021 (13 vs 17), oncology held steady at nearly 30% of all novel approvals in both years.
Dermatology, however, went from two novel approvals in 2021 to six in 2022, or from a 6% share of 2021 novel approvals to 13% in 2022. Dermatology joined the perennial second-place therapy area, neuroscience, and the broad infectious disease space in a three-way tie for the second-most novel approvals of 2022. (See infographic below.)
The Center for Drug Evaluation and Research’s 37 new molecular entities and novel biologics combined with eight novel biologics from the Center for Biologics Evaluation and Research to make up the 45 products in 2022 class of novel agents, a lower total than the highs of the past five years but average in the longer term. (Also see "With 37 Novel Approvals in 2022, US FDA CDER’s Five-Year Hot Streak Comes To An End; Gene Therapies Carry CBER To 8 Novel Approvals" - Pink Sheet, 2 Jan, 2023.)
Different Therapy Areas Tell Different Approval Stories
The growth narrative that had emerged from a decade of novel approval counts that repeatedly hit new highs came to an end in 2022, when the Center for Drug Evaluation and Research approved 37 new molecular entities and novel therapeutic biologics – a comedown from CDER's average of 42.8 novel approvals a year from 2013-2022. The Center for Biologics Evaluation and Research contributed eight novel biologics, right around CBER's average of 8.3 novel agents/year.
Each therapeutic category, however, wrote its own story, from new classes of immunotherapy emerging from the innovative oncology pipeline to big ambitions in dermatology and a conservative year in neuroscience after the Aduhelm controversy.
Of course some of the most commercially significant and medically important novel approvals of 2022 came from therapeutic areas with more sluggish pipelines, like metabolic disease, or intrinsically narrow specialization, like ophthalmology.
Only two novel diabetes treatments cleared the agency, but both were first-in-class agents. Provention Bio, Inc.’s Tzield (teplizumab-mzwv) became the first product ever indicated to delay onset of symptomatic, or Stage 3, type 1 diabetes in patients at pre-symptomatic Stage 2 T1D.
Eli Lilly and Company’s glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) agonist Mounjaro (tirzepatide) had one of the most successful launches of 2022, despite entering the highly competitive type 2 diabetes market. Mounjaro “activates two hormone receptors, which leads to improved glycemic control,” CDER highlighted in its summary 2022 report.
Similarly, Genentech, Inc.’s Vabysmo (faricimab-svoa) brought a dual mechanism of action – the bispecific antibody targets angiopoietin-2 (Ang-2) as well as the more familiar target of vascular endothelial growth factor-A (VEGF-A) – into the crowded acute macular degeneration and diabetic macular edema market. Vabysmo ended the year on track for blockbuster status. (Also see "Fewer Drug Launches In 2022, But Standouts Among Them" - Scrip, 3 Jan, 2023.)
Showing some accurate forecasting ability, both Lilly and Genentech applied a priority review voucher (PRV) to their applications, helping Mounjaro and Vabysmo to approvals after review of eight months of review instead of the 12-month standard review timeline for novel agents.
Below is the Pink Sheet breakdown of how several disease categories faired last year. For a complete listing of FDA’s 2022 novel approvals, see the Pink Sheet FDA Performance Tracker’s Novel CDER Approvals and Novel CBER Approvals.
Immuno-Oncology’s Expanding Universe
In the eight years since the approval of the first PD-1 checkpoint inhibitor, Merck & Co., Inc.’s Keytruda (pembrolizumab), immunotherapy has grown into a keystone of cancer therapy. The rush of new PD-1/L1 inhibitors has slowed as the field matures – and as the burgeoning Chinese pharma industry wrestles with FDA demands for trials in populations relevant to the US – but 2022 saw multiple offshoots.
The approval of Bristol Myers Squibb Company’s LAG-3 blocking antibody relatlimab-rmbw, combined with the PD-1 inhibitor Opdivo (nivolumab) to make Opdualag, introduced the first new class of checkpoint inhibitor since the PD-1/L1s, the FDA noted. AstraZeneca PLC introduced its own CTLA-4 inhibitor, Imjudo (tremelimumab-actl), for use with its PD-L1 inhibitor Imfinzi (durvalumab); indicating the strategic importance of Imjudo to AZ, the company applied a PRV to the application.
Immunocore, Ltd.’s T-cell receptor bispecific engager peptide Kimmtrak (tabentafusp-tebn) was first T-cell receptor therapeutic to clear the FDA, the company noted. It was quickly followed by two bispecific antibodies, Genentech’s Lunsumio (mosunetuzumab-axgb) and Johnson & Johnson’s Tecvayli (teclistamab-cqyv).
CBER’s gene therapy approvals also included two products focused on immune response to cancer: Ferring Pharmaceuticals’s Adstiladrin (nadofaragene firadenovec-vncg), which promotes production of interferon alfa-2b in the bladder, and Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel), a chimeric antigen receptor T-cell (CAR-T) therapy.
Two of the novel immunotherapies – Opdualag and Kimmtrak – qualified for the FDA’s popular Real-Time Oncology Review (RTOR) pilot program, which opened to novel agents in December 2018. The RTOR program also produced 2022 approvals for two NMEs from the older targeted therapy field, Taiho Pharmaceutical Co. Ltd.’s Lytgobi (futibatinib) and Mirati Therapeutics, Inc.’s Krazati (adagrasib).
The four RTOR novel approvals in 2022 is down from six last year, but the share of RTOR among novel approvals is holding steady at around 30%.
Dermatology Sees A Rare Missed Goal Date
Pfizer Inc.’s oral Janus kinase (JAK) inhibitor Cibinqo (abrocitinib) was one of the first approvals of 2022 – because the NDA missed its 2021 goal date while FDA wrestled with safety concerns for the JAK class in the wake of heart attack and cancer safety signals seen in a postmarketing trial of one of the first JAK inhibitors to reach the US market, the company’s own Xeljanz (tofacitinib).
Cibinqo’s indication for moderate to severe atopic dermatitis was restricted to use after systemic therapy, including biologics, after the agency’s class safety review relegated JAK inhibitors to later lines of therapy. The JAK class is widely used across immunologically-driven dermatology and rheumatology conditions.
Cibinqo was the only CDER approval to miss its user fee goal date, which is impressive considering the agency’s COVID-19 pandemic policy of delaying action until inspections could be carried out if no other issues warranted a complete response letter. Nonetheless, at least five products are still stalled by China’s COVID-19 policies, including multiple novel PD-1 inhibitor candidates. (Also see "With 37 Novel Approvals in 2022, US FDA CDER’s Five-Year Hot Streak Comes To An End; Gene Therapies Carry CBER To 8 Novel Approvals" - Pink Sheet, 2 Jan, 2023.)
Cibinqo was also one of the two dermatology therapies to receive a breakthrough therapy designation, along with Boehringer Ingelheim GmbH’s interleukin 36-targeting Spevigo (spesolimab-sbzo) to treat flares of generalized pustular psoriasis. The two products are markedly different: an oral small molecule from an established class for a common condition, and a first-in-class monoclonal antibody for a rare, potentially life-threatening disease.
Neurology Rules Neuroscience
Orphan neurologic conditions dominated the novel approvals from the FDA’s Office of Neuroscience, which lodged an above-average percentage of drugs for rare diseases in 2022.
CDER’s neurology division then issued the FDA's first approval of 2023, the 6 January accelerated approval of Eisai Co., Ltd./Biogen, Inc.’s Leqembi (lecanemab-irmb) for the decidedly non-orphan Alzheimer's disease. With a spotlight on the Alzheimer’s space after the FDA’s controversial 2021 accelerated approval of Biogen’s Aduhelm (aducanumab-avwa), the upcoming year promises a year full of cost, value and reimbursement debates.
In 2022, however, the neurology division was weighted toward drugs in established classes for smaller populations, including Alnylam Pharmaceuticals Inc.’s RNA interference therapy Amvuttra (vutrisiran) for polyneuropathy of hTTR amyloidosis and TG Therapeutics’ Briumvi (ublituximab-xiiy) for multiple sclerosis, which both received standard review.
Amylyx Pharmaceuticals, Inc.’s Relyvrio (sodium phenylbutyrate and taurursodiol) survived an unusual two advisory committee reviews in one review cycle before getting the nod to treat amyotrophic lateral sclerosis. Somewhat like Alzheimer’s disease, ALS received significant public attention after controversial drug issues have arisen.
In the end, FDA’s neurology division will receive a funding boost under the December 2022 omnibus appropriations bill, including the Act for ALS grant program. (Also see "US FDA Neurology Drugs Program Gains Boost In FY 2023 Funding Bill Amid Calls To Clarify Development Policies" - Pink Sheet, 3 Jan, 2023.)
One of the two first-in-class approvals went to Marinus Pharmaceuticals, Inc.’s Ztalmy (ganaxolone), the first neuroactive steroid from the epalon class. Ztalmy’s indication is also fairly novel: cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) was only given an ICD10 code from the World Health Organization in 2020 after previously having been considered a variant of Rett syndrome.
The psychiatry end of the Office of Neuroscience produced just one novel approval in 2022, Idorsia's insomnia therapy Quviviq (daridorexant). Another psychiatry product, Levo Therapeutics, Inc.’s orphan nasal carbetocin for distress behaviors of Prader-Willi syndrome, received the only complete response letter for a novel neuroscience agent in 2022. (Also see "US FDA’s Use Of CRLs Hit A High Note In 2022: One-Third Of Novel Agent Decisions Were Not Approvals" - Pink Sheet, 9 Jan, 2023.)
A Range Of Approaches To Infectious Disease
The FDA’s 2022 approvals in infectious disease were evenly split between CDER and CBER, and spanned technologies from small molecule drugs to an mRNA vaccine. Only two products, Mycovia Pharmaceuticals, Inc.’s fungal CYP51 inhibitor Vivjoa (oteseconazole) and Phathom Pharmaceuticals, Inc.’s Voquezna Double and Triple Paks (vonoprazan and amoxicillin, with and without clarithromycin) for Helicobacter pylori infection, qualified for the FDA’s Qualified Infectious Disease Product (QIDP) designation.
Half of the infectious disease approvals went to products targeting viral infections. CBER contributed vaccines for viruses new (Moderna, Inc.’s Spikevax for COVID-19) and old (GSK plc’s measles, mumps and rubella vaccine Priorix, which has been available in Europe for 25 years). CDER cleared Gilead Sciences, Inc.’s latest antiretroviral for HIV, Sunlenca (lenacapavir), a first in class, breakthrough designee.
The lone antifungal, Vivjoa, received the first indication for prevention of recurrence of vulvovaginal candidiasis in women not of reproductive potential; then, on 30 November 2022, the FDA granted its second RVVC approval, a new supplemental indication for Scynexis, Inc.’s triterpenoid antifungal Brexafemme (ibrexafungerp) without the reproductive restriction.
The approval came too late for Scynexis, which has refocused and is looking to outlicense Brexafemme, illustrating the commercial challenges of launching new anti-infectives even if they address well-known unmet needs.
Blood Disorders
The FDA’s only approved five novel agents in non-malignant hematology approvals, but they punch above their weight with high levels of expedited review programs and novelty. The CDER website’s section on “notable approvals” includes just six novel agents in the 12 selected 2022 approvals, but three of them are blood disorder treatments.
The “notable approvals” include two first-in-class products for rare anemias, Sanofi’s classical complement inhibitor Enjaymo (sutimlimab-jome) and Agios Pharmaceuticals, Inc.’s pyruvate kinase activator Pyrukynd (mitapivat). Enjaymo, which holds a BTD, is the only product approved to reduce need for blood transfusions due to hemolysis in patients with cold agglutinin disease; Pyrukynd is the first disease-modifying therapy for hemolytic anemia in adults with pyruvate kinase deficiency.
The FDA website also highlighted CTI BioPharma Corp.’s Vonjo (pacritinib), which the sponsor describes as “the first approved therapy to specifically address the needs of adult cytopenic myelofibrosis patients.” Vonjo received the only novel accelerated approval in non-malignant hematology in 2022.