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.