FDA Decision On Tolebrutinib

Last week, we posted on Facebook that the FDA has decided to not approve tolebrutinib for the treatment of secondary progressive multiple sclerosis, despite positive Phase 3 trial results.  In this article, we are going to look at the stated reasons and the likely next steps.

The FDA Decision

The FDA published their Complete Response Letter (CRL) to Sanofi, which highlights two key points:

Firstly, there were serious concerns raised about the risk of liver damage caused by the treatment, referred to as Drug Induced Liver Injury (DILI). These liver issues were a known problem during the trial, resulting in participants being monitored on a weekly basis.  However, the FDA notes that the “benefit-risk assessment must assume that there will be severe and potentially fatal cases of DILI in the postmarketing setting, even with a REMS (Risk Evaluation and Monitoring Strategy) requiring weekly laboratory monitoring”.

Secondly, there were also questions about the effectiveness of tolebrutinib to slow disability accumulation independent of relapse activity and which participants were most likely to benefit from the treatment. This second part was seen as particularly critical, as “given the serious and unusually high risk of severe DILI, it is critical to have certainty about efficacy in a population in whom this level of DILI risk could be considered acceptable”.

What next?

So what was the reaction to this decision and what are the next steps?  Firstly, it is fair to say that, based on their press release, Sanofi were surprised by this outcome.

“Today’s FDA decision is a significant and meaningful change in direction from the feedback the agency previously provided to Sanofi. 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. 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” said Houman Ashrafian, Executive Vice President, Head of Research & Development at Sanofi.

However, the most important part of the quote is probably what comes next…

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

This indicates that Sanofi will be conducting further analysis on the data received from their Phase 3 clinical trial of tolebrutinib, to be able to provide more information to the FDA about the population of people living with secondary progressive MS that had the most significant benefits from the treatment.  As with all new therapies, the final decision will be based on whether the potential benefits outweight the potential risks.

We will continue to follow this story and provide any updates as they become available.

You can find us on Facebook, Twitter, YouTube, Instagram and LinkedIn.