Principia Biopharma, Inc.

Corcept Therapeutics\' stock lost half its value in the wake of the FDA\'s decision.\n The festive period brought some unwanted post for both Sanofi and Corcept Therapeutics in the form of FDA rejections for the companies’ respective drug applications.Sanofi revealed Dec. 24 that the FDA had knocked back its approval submission for tolebrutinib in non-relapsing secondary progressive multiple sclerosis (nrSPMS). The agency’s decision will have come as an especially nasty shock for the French pharma, which only weeks earlier had been told by the FDA that the approval decision would no longer be made in time for a previously confirmed Dec. 28 deadline.In secondary progressive MS, patients typically have been diagnosed with relapsing MS but have stopped having relapses and instead experience so-called “disability accumulation.” Despite advances in MS care, unmet need remains in this treatment setting as options are limited, according to the company.Back in March, Sanofi picked up an FDA priority review for the nrSPMS filing and touted an expected approval decision by Sept. 28. But, as that date neared in the fall, the drugmaker disclosed a three-month delay due to its submission of “additional analyses” during the review, which constituted a major amendment to the application by the FDA\'s standards.With the amended deadline nearing, Sanofi then announced Dec. 15 that it had been warned by the FDA not to expect any new guidance for the application until March 2026.With a decision no longer expected anytime soon, it means that the CRL last week marked a “significant and meaningful change in direction from the feedback the agency previously provided to Sanofi,” the pharma’s head of R&D Houman Ashrafian, Ph.D., said in a Dec. 24 statement. “We are very disappointed by the FDA\'s action,” Ashrafian continued. “Disability progression remains a large unmet medical need in MS, and tolebrutinib was previously awarded breakthrough therapy designation by the FDA in recognition of its potential to address this critical gap.”“We believe that the FDA should also take the advice of scientific experts, clinicians, and patients in this matter to ensure all perspectives are considered,” he added. “We remain committed to working with the FDA to find a path forward for tolebrutinib and ultimately serve the MS community.”Sanofi didn’t elaborate further on the FDA’s rationale behind its change of heart.The rejection is only the latest in a string of setbacks for tolebrutinib, which Sanofi acquired as part of its $3.7 billion buyout of Principia Biopharma back in 2021. The following year, the FDA put a group of late-stage studies under a partial clinical hold so it could review reports of drug-induced liver injury.Then, in 2023, Sanofi reported that the drug failed two out of three late-stage studies in MS but that it still planned to seek an approval in nrSPMS thanks to its clinical win in that indication. The mixed bag of results ultimately dented the med\'s therapeutic scope, and Sanofi removed tolebrutinib\'s use in relapsing MS from its pipeline early this year.The company only recently disclosed that the phase 3 Perseus study missed the mark in patients with primary progressive MS, leading Sanofi to decide against seeking regulatory approval in that specific indication as well. Corcept \"surprised and disappointed\" The CRL that landed in Corcept’s post box over the holidays will have been an equally unwelcome surprise. The company had submitted its approval application for its lead asset relacorilant on the back of a phase 3 win last year for the antiglucocorticoid in the Grace study of patients with Cushing’s syndrome.According to Corcept, the FDA “acknowledged that Corcept’s pivotal Grace trial met its primary endpoint and that data from the company’s Gradient trial provided confirmatory evidence.”However, the agency “concluded it could not arrive at a favorable benefit-risk assessment for relacorilant without Corcept providing additional evidence of effectiveness,” the biotech explained in a Dec. 31 release. Corcept CEO Joseph Belanoff, M.D., said the company was “surprised and disappointed by this outcome.”“I am confident we will find a way to get relacorilant to the patients it could help,” Belanoff added. “We will meet with the FDA as soon as possible to discuss the best path forward.”Investors didn’t appear reassured, wiping 50% of the value of the company’s stock so it ended Thursday’s trading on $34.80 compared to a Wednesday closing price of $70.20.The FDA has penciled in a July 2026 decision date for a separate approval application from Corcept for relacorilant in platinum-resistant ovarian cancer. 

The European Commission has signed off on Sanofi's Wayrilz (rilzabrutinib), clearing the oral BTK inhibitor for adults with immune thrombocytopenia (ITP) who are refractory to other therapies. The Tuesday approval marks the first time the drug class has been authorised for the condition in the EU.The decision follows a recent positive opinion by the European Medicines Agency's drug advisory body and comes about four months after the US approved it for persistent or chronic ITP.The EU approval is based on results from the Phase III LUNA 3 trial, which enrolled 202 adults with persistent or chronic ITP. In the study, 23% of patients receiving Wayrilz achieved durable platelet response — defined as platelet counts of at least 50,000/μL for eight of the final 12 weeks of the blinded treatment period — compared to none in the placebo arm. Treated patients also reached their first platelet response more quickly, with a median time of 36 days, and maintained responses for longer periods than those given placebo (see – KOL Views Q&A: Sanofi's rilzabrutinib can contend in ITP but competition fierce and more footsteps approaching).Beyond platelet counts, patients treated with Wayrilz also saw a 10.6-point improvement in overall quality-of-life versus a 2.3-point improvement among placebo recipients."Wayrilz has a differentiated mechanism of action, enabling multi-immune modulation to address the underlying pathology of ITP," Brian Foard, Sanofi's head of specialty care, said in a release. Additional regulatory reviews are ongoing in Japan and China.Wayrilz landed in Sanofi's portfolio through its $3.7-billion takeover of Principia Biopharma in 2020 (see – Vital Signs: Sanofi builds momentum for its I&I bets). The drug is under investigation for other indications besides ITP; it's being studied in a Phase III trial for warm autoimmune haemolytic anaemia and sickle cell disease, and in a Phase II study for IgG4-related disease and Graves' disease.

Sanofi has shown persistence with its multiple sclerosis hopeful tolebrutinib, but a potential approval is going to have to wait several more months.\n After spending the year angling for a new approval in multiple sclerosis, Sanofi\'s stockings may hang empty this holiday season—at least when it comes to tolebrutinib in non-relapsing secondary progressive MS (nrSPMS). The FDA doesn\'t intend to make a decision on the company\'s filing for tolebrutinib in nrSPMS by Dec. 28 as previously planned, Sanofi said in a Dec. 15 press release. Back in March, Sanofi picked up an FDA priority review for the filing and touted an expected approval decision by Sept. 28. But, as that date neared in the fall, the drugmaker disclosed a three-month delay due to its submission of \"additional analyses\" during the review, which constituted a \"major\" amendment to the application by the FDA\'s standards.Now, with the second consecutive delay in the books, Sanofi expects to hear new guidance from the FDA by the end of March, the company said in its release.But the delay wasn\'t the only piece of bad news for Sanofi and its tolebrutinib ambitions Monday. In addition, the company disclosed that the phase 3 Perseus study missed the mark in patients with primary progressive MS (PPMS). That study assessed the ability of the BTK inhibitor to delay time to six-month composite confirmed disability progression versus placebo.Sanofi won\'t seek regulatory approval for the drug in PPMS, the company said Monday. So continues the rocky path for the drug, which Sanofi picked up in its $3.7 billion buyout of Principia Biopharma back in 2021. The following year, the FDA put a group of late-stage studies under a partial clinical hold so it could review reports of drug-induced liver injury.Two years on from that, Sanofi reported that the drug failed two out of three late-stage studies in MS but that it still planned to seek an approval in nrSPMS thanks to its clinical win in that indication. The mixed bag of results ultimately dented the med\'s therapeutic scope, and Sanofi removed tolebrutinib\'s use in relapsing MS from its pipeline early this year.In secondary progressive MS, patients typically have been diagnosed with relapsing MS but have stopped having relapses and instead experience \"disability accumulation,\" Sanofi explained in its press release. Despite advances in MS care, unmet need remains in this treatment setting as options are limited, according to the company.