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Still under partial hold, Sanofi makes case for safety of MS med from Principia buyout

2023-04-28

临床3期临床2期并购上市批准临床结果

The BTK inhibitor—which was acquired in Sanofi’s $3.7 billion takeover of Principia Biopharma in 2021—was flagged by the FDA last summer after cases of drug-induced liver injury were reported.

SanoBTKs multiple sclerosis med tolebrutSanofiay be under a partial FDA clPrincipia Biopharmaeports of liver injury in a FDAdful of phase 3 studies, butdrug-induced liver injury French pharma from collecting some data to make the case for efficacy and safety.

SanofiK imultiple sclerosis acqutolebrutinibfi’s $3.7 billion takeover of Principia Biopharma in 2021—wliver injuryy the FDA last summer after cases of drug-induced liver injury (DILI) cropped up. Because of the safety concern, the regulatory agency slapped a partial clinical hold on phase 3 trials —four MS trials and a phase 3 myasthenia gravis (MG) program, the latter of which the French pharma ultimately abandoned.

FDA BTKicials imposed the restrictions bSanofi of “a limited number of casPrincipia Biopharmaliver injury,” Sanofi said aFDAhe time. The company added tdrug-induced liver injury (DILI)t complications known historically to predispose to drug-induced liver injury,” and the elevated laboratory values were reversible after treatmentmyasthenia gravis (MG)

FDAnofi continues to monitor liver safety in the ongoing trials and is working tdrug-induced liver injuryes SanofiI that have been identified with tolebrutinib exposure in phase 3 studies,” Erik Wallström, M.D., Ph.D., Sanofi’s global hdrug-induced liver injuryerce Biotech in an emailed statement.

NSanofig-term extension data presented at the American Academy of Neurology Annual Meeting in Boston gives a deDILI look at tolebrutinib's safety atolebrutinib On Monday, phase 2b data was shared from a 2.5-year-long stSanofiat split patients with relapsing MS into two groups. Part A is a double-blind study in which patients received 5, 15, 30, or 60 mg of tolebrutinib each day, while part B is an open-label study in which patients received 60 mg per day.

Researchers didn’t observe any dosing-related treatment-emergent adverse events (TEAEs) or serious adverse events (AEs) in ptolebrutinibo safety signals emerged for patients switching to 60 mg in part B. The most common TEAEs reported were COVID-19relapsing MS% of patients experienced, and headache, which 13.6% of patients reported.tolebrutinib

The study had an 85.6% retention rate (107 patients) at the 2.5-year mark, with “lack of efficacy” being the top reason for treatment discontinuation, as cited by five patients.COVID-19 headache

A hallmark of MS is that patients often relapse, so efficacy outcomes included annualized relapse rate and change from baseline on a disability status scale. For 124 participants receiving 60 mg of tolebrutinib daily for more than eight weeks, 73.4% of patients remained relapse-free. For the duration of the long-term extension, mean disability status levels remained stable. Overall, the data suggests 60 mg of tolebrutinib taken daily still demonstrates a favorable safety profile and is tied to low relapse rate and stable disability, according to Sanofi.

Despite the ongoing hold, Sanofi remains on track to submit the drug for approval to the FDA in relapsing MS in 2024, Wallström confirmed. Under the partial hold, enrollment at U.S. sites stopped antolebrutinib suspended in existing subjects who had been in the study for less than 60 days. However, three of the four MS phase 3 trials were already enrolled and aren’t impacted by the hold, a company spokespersontolebrutinib Biotech.Sanofi

The pharma’s phase 3 trialSanofielapsing MS, dubbed Gemini I and Gemini II, are fully enrFDAed arelapsing MSmated completion dates in September and August of this year, respectively. The trials are evaluating 60 mg daily doses of tolebrutinib.

Sanofi is still working with threlapsing MSresolving the partial clinical hold, according to the spokesperson. Previously, Sanofi said new information requested by the FDA would be submitted at the end of September 2022 in hopes ttolebrutinibd be lifted shortly after.

SanofiA wants a deeper understanding of the patient population and benefit-risk data for the investigational drug, Sanofi’sSanofil Head of R&D Dietmar Berger told analyFDA on an earnings call yesterday.

The FDArma is steamrolling forward in MS, aiming the Principia med at the indication since bowing out of the myasthSanofiravis space in February, when the French pharma discontinued its phase 3 clinical trial given the competitive landscape.

The discontinuation “was based on challenges in enrolling participants from a small patient population (MG ismyasthenia gravisin a placebo-controlled trial given the number of newly approved products,” Wallström told Fierce Biotech. “The decision was not based on any assessment of the clinical promise of tolebrutinib in MG.”

The long-term condition that causes muscle weakness has emerged as a focus for several drug developers in recent years. Alexion, now part of AstraZeneca, snagged approval for Soliris in the indication in 2017 and then gained another FDA nod for Ultomiris last year. Meanwhile, argenx secured U.S. approval tolebrutinibin 2021.

Another competitor that has yet to hmuscle weaknesss UCB, which has zilucoplan and rozanolixizumab currently under FDA rAlexionJohnson & JohnAstraZenecaclosely behind, with the phase 3 study of challenger nipocalimab scheduled for prFDAry compleUltomirishe end of this year.argenx Vyvgart

The MS space also has plenty of competition approved UCB in developmzilucoplanding rozanolixizumabera, Genentech’s Ocrevus and Johnson & Johnsonibb’s Zeposia. Sanofi also has its own approved MS asset callnipocalimab a daily oral therapy for relapsing MS.