No Christmas present for Sanofi, as FDA turns down MS drug

Sanofi went into the Christmas break with news of a takeover deal to boost its vaccines business, even as the FDA sent an early complete response letter for its oral multiple sclerosis candidate tolebrutinib.

The timing of the decision came as a surprise, as the FDA delivered its verdict on Sanofi's application months earlier than expected. The French drugmaker had said just days earlier that it was expecting the review to extend well into the first quarter of 2026.

The outcome of the review was arguably less surprising, however, as Sanofi has already had other setbacks with tolebrutinib, an oral BTK inhibitor, including a failed pivotal trial in primary progressive MS (PPMS).

That scuppered Sanofi's plans for filing tolebrutinib in PPMS, and the FDA has now slammed the brakes on its efforts to get the drug approved for non-relapsing secondary progressive MS (nrSPMS), having already delayed its decision deadline by three months from 28th September to 28th December.

It also seems to have wrong-footed Sanofi, which said in the middle of this month that – at the request of the US regulator – it had submitted an expanded access protocol for tolebrutinib in nrSPMS.

Houman Ashrafian, head of R&D at Sanofi, said in a statement that the complete response letter (CRL) "is a significant and meaningful change in direction from the feedback the agency previously provided to Sanofi," alluding to discussions with the FDA that took place ahead of its earlier announcement that a decision was likely to be delayed into 2026.

"We are very disappointed by the FDA's action. 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," added Ashrafian.

"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. We remain committed to working with the FDA to find a path forward for tolebrutinib and ultimately serve the MS community."

In the HERCULES trial, tolebrutinib was able to delay the time to six-month disability progression by 31% compared to placebo in patients with nrSPMS, with the welcome positive result coming after the drug failed two phase 3 trials in relapsing form of MS.

The decision could hand an advantage to Roche, whose rival oral BTK inhibitor fenebrutinib has hit the mark in phase 3 trials involving patients with both relapsing MS and PPMS, and is being prepared for filings next year.

Sanofi has claimed one approval for tolebrutinib in nrSPMS – in the United Arab Emirates (UAE) – and is still waiting to hear from regulators elsewhere in the world, including Europe.

Image by Gerd Altmann from Pixabay