FDA Grants Priority Review for Lecanemab, FDA AdComm to Reconvene on AMX0035, Tolebrutinib Trials Suspended Over Safety

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Welcome to this special edition of Neurology News Network. I’m Marco Meglio.

After officially submitting it this May, the FDA announced they have accepted and granted priority review to Eisai and Biogen’s biologics license application (BLA) of lecanemab (BAN2401), an investigational agent to treat mild cognitive impairment (MCI) because of Alzheimer disease (AD). The companies have been given a Prescription Drug User Fee Act (PDUFA) action date of January 6, 2023.Submitted under the accelerated approval pathway—the same pathway that Biogen’s aducanumab (Aduhelm) was approved under in 2021—the application was supported by data from the phase 2b proof-of-concept clinical trial, known as Study 201. Additionally, the FDA will consider and review results from the ongoing phase 3 Clarity AD study, which will serve as complimentary data to verify the clinical benefit of lecanemab post approval. Dependent upon the results of Clarity AD, Eisai will submit for traditional approval of lecanemab to the FDA before the end of the first quarter in 2023. Lecanemab, an antiamyloid beta (Aß) protofibril antibody, is designed to neutralize and eliminate soluble toxic Aß aggregates that are thought to contribute to the neurodegenerative process in AD.

According to a new announcement, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee is planning to reconvene on September 7, 2022, to discuss the new drug application (NDA) for AMX0035 (Amylyx Pharmaceuticals), an investigational agent in review for amyotrophic lateral sclerosis (ALS), weeks before the scheduled PDUFA date.The news comes less than a month after the agent received approval in Canada, making it the first new therapy for the disease since 2018.2 It also comes a few months after the original discussion by the committee. This second time meeting of the panel will also feature conversation assessing whether AMX0035 demonstrated a significant enough efficacy in the phase 2/3 CENTAUR study (NCT03127514) and open-label extension, the basis of the NDA. AMX0035, an orally administered fixed-dose coformulation of sodium phenylbutyrate-taurursodiol, originally had a PDUFA target action date of June 29, 2022, which was then pushed back early that month to September 29, 2022, to allow more time for the FDA to review data.

The FDA has placed a partial clinical hold on Sanofi's phase 3 clinical trials for tolebrutinib, its Bruton tyrosine kinase (BTK) inhibitor being evaluated for the treatment of multiple sclerosis (MS) and myasthenia gravis.The hold was placed based on reported cases of drug-induced liver injury in patients who received the study drug in the ongoing trials, of which there are 5: GEMINI 1 and 2 in relapsing MS; PERSEUS in primary progressive MS (PPMS); HERCULES in nonrelapsing secondary progressive MS (SPMS); and URSA in generalized myasthenia gravis. As such, new enrollment in the studies is paused, and any participant who has been in a study for less than 60 days has been instructed to suspend the study drug. Notably, Sanofi revised global study protocols in May of this year to both update safety monitoring and enrollment criteria to exclude those with preexisting factors related to hepatic dysfunction. Study sites outside of the US remain in active enrollment.

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