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.
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