After FDA rejection, Sanofi’s BTK inhibitor wins EU approval

Why it matters: SPMS is a stage of MS in which disability steadily worsens, often without the relapses that define earlier phases of the disease.

• Cenrifki does not reverse SPMS, but in a pivotal Phase III trial, it slowed the worsening of disability in a patient group with no approved treatment options.

Zoom in: Cenrifki is a Bruton’s tyrosine kinase (BTK) inhibitor – a drug class better known from cancer treatment but increasingly being tested in autoimmune and inflammatory diseases.

• Brain-penetrant BTK inhibitors such as Cenrifki can reach immune cells behind the blood-brain barrier, offering a way to target chronic inflammation in the central nervous system.

Backstory: Sanofi acquired tolebrutinib, then known as SAR442168, through its $3.7 billion acquisition of Principia Biopharma in 2020. At the time, analysts at Jefferies estimated the drug could generate peak global sales of about $2 billion.

Yes, but: The EU approval follows a U.S. setback. In December 2025, the FDA issued a complete response letter for tolebrutinib in non-relapsing SPMS (nrSPMS), saying a favorable benefit-risk profile could not be established. The agency cited uncertainty over the drug’s efficacy and concerns over serious liver injury.

By the numbers: In the Phase III HERCULES study, tolebrutinib reduced the risk of six-month confirmed disability progression by 31% for patients with nrSPMS versus placebo.

• Tolebrutinib raised safety concerns related to liver injury. 5 percent of patients taking tolebrutinib had elevated liver enzymes compared with none on placebo.
• Most liver enzyme elevations normalized after treatment discontinuation.
• One patient treated with tolebrutinib died from complications related to liver failure.

Another setback: Separately, tolebrutinib failed the Phase III PERSEUS trial in primary progressive MS (PPMS) in December 2025. The study did not meet its primary endpoint of delaying six-month confirmed disability progression compared with placebo, and Sanofi said it would not pursue regulatory registration in PPMS.

What’s next: Sanofi said Cenrifki will launch in Germany this year. The drug is also approved in the United Arab Emirates since August 2025.