One of the most significant pieces of regulatory news fell just beyond the end of 2022 as the US Food and Drug Administration (FDA) gave an accelerated approval to Eisai-Biogen’s lecanemab on the basis of amyloid plaque clearance. A second anti-plaque antibody, Lilly’s donanemab, may receive an accelerated approval in early February. Preventative antibodies outside Alzheimer’s disease also took a front seat in the approvals list from the last quarter of 2022, with the FDA giving the go-ahead to both AstraZeneca and Sanofi’s Beyfortus (nirsevimab) for respiratory syncytial virus (RSV) infections in neonates and Provention Bio’s Tzield (teplizumab), which slows progression to full-blown type I diabetes. Beyfortus targets a highly conserved region of the RSV F protein, preventing virus from entering cells; through modifications to the Fc region, it has an extended half-life, allowing a single administration to provide season-long blocking of virus. In Tzield, Fc modifications reduce receptor binding to the Fc region, slowing the loss of insulin-producing cells. The FDA also granted accelerated approval in non-small-cell lung cancer for Mirati Therapeutics’ Krazati (adagrasib), an irreversible covalent binder of the KRAS oncoprotein. The fortunes of small-molecule splice modulators in Huntington’s disease reversed, however, with an FDA clinical hold for PTC Therapeutics’ PTC518 and a Data Monitoring Committee recommendation to pause the phase 2b trial of Novartis’s branaplam following potential peripheral neuropathies in some patients. 2Q23 will see some interesting new approaches come before regulators. In May the FDA is looking at Sarepta Therapeutics’ adeno-associated virus (AAV)-delivered microdystrophin for Duchenne muscular dystrophy, Byondis’s prodrug-linked HER2 antibody trastuzumab duocarmazine, and ImmunityBio’s interleukin (IL)-15 superagonist nogapendekin alfa (Anktiva). Before that, in April, a decision is expected on Eli Lilly’s p19-selective antibody mirikizumab in ulcerative colitis. Despite a complete response letter back in May 2022, UCB shared impressive data on its anti-IL17 bispecific bimekizumab (Bimzelx) in December for psoriatic arthritis. As well as the hopeful molecules for Alzheimer’s disease, a new generation of anti-inflammatory antibodies may be emerging.
Drug/company | Indication | Drug information |
|---|
Beyfortus (nirsevimab)/AstraZeneca and Sanofi | RSV prevention | 11/09/2022 EMA approved this IgGκ1 mAb targeting the highly conserved θ region of the pre-fusion RSV F protein. Modifications of the Fc region extend the half-life of the antibody, potentially providing season-long RSV prevention. |
Imjudo (tremelimumab) combined with Imfinzi (durvalumab)/AstraZeneca | Hepatocellular cancer | 11/10/2022 FDA approved the checkpoint inhibitor combination of tremelimumab-actl, a CTLA-4 blocking human IgG2 mAb, with durvalumab, a PD-L1 blocking IgG1 antibody. |
Tzield (teplizumab)/Provention Bio | Diabetes mellitus type 1 | 11/17/2022 FDA approved this humanized IgG1 mAb engineered in the Fc region with leucine-to-alanine substitutions at residues 234 and 235 to reduce Fc receptor binding, directed against the CD3 ε-chain expressed on mature T lymphocytes to moderate the loss of insulin-producing cells in the pancreas. |
Hemgenix (etranacogene dezaparvovec)/CSL Behring | Hemophilia B | 11/22/2022 FDA approved this AAV5 vector gene therapy with the Padua overexpression variant of the F9 gene. |
Rebyota (microbiota suspension)/Ferring Pharmaceuticals | Recurrent Clostridioides difficile-associated diarrhea | 11/30/2022 FDA approved this pathogen-screened fecal microbiota suspension derived from healthy donors for rectal administration |
Adstiladrin (nadofaragene firadenovec)/FKD Therapies | Bladder cancer | 12/16/2022 FDA approved this non-replicating recombinant adenovirus serotype 5 vector that expresses a transgene encoding human interferon α2b, delivering the protein to the bladder epithelium. |
Tecvayli (teclistamab)/Janssen | Multiple myeloma | 10/25/2022 FDA granted accelerated approval to this T cell engager, a humanized BCMA × CD3 DuoBody IgG4 mAb. |
Elahere (mirvetuximab soravtansine)/Immunogen | Ovarian cancer | 11/14/2022 FDA granted accelerated approval for this antibody–drug conjugate consisting of the cytotoxic maytansinoid DM4 covalently linked to the humanized mAb M9346A, which binds to folate receptor 1. |
Krazati (adagrasib)/Mirati Therapeutics | Non-small-cell lung cancer | 12/12/2022 FDA granted accelerated approval for this small-molecule irreversible covalent inhibitor of G12C mutated KRAS. |
- BCMA, B cell maturation antigen CTLA-4, cytotoxic T lymphocyte-associated protein 4; EMA, European Medicines Agency; Fc, immunoglobulin constant region; IgG, immunoglobulin G; KRAS, rat sarcoma viral oncogene homolog; mAb, monoclonal antibody; PD-L1, programmed cell death ligand-1; RSV, respiratory syncytial virus. Source: BioMedTracker, a service of Sagient Research (http://www.biomedtracker.com).
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