EU Approval Opens Doors for Cenrifki Amid US Hurdles

Europe’s drug advisory committee recommended approval of Sanofi’s (SNY) Cenrifki for secondary progressive multiple sclerosis on April 24, a pivotal catalyst that partially offsets a costly FDA rejection and a nearly €1.7 billion impairment charge.

For deal-focused investors, the CHMP positive opinion signals that Sanofi’s $3.7 billion acquisition of Principia Biopharma in 2020 may yet generate meaningful commercial returns, even as the U.S. market remains closed for now.

Key Takeaways

CHMP backs Cenrifki; formal European Commission decision expected within months.
FDA rejected tolebrutinib in January 2026 citing liver-injury risk.
Sanofi booked a ~€1.7 billion impairment charge tied to tolebrutinib setbacks.

Regulatory Context & Market Backdrop

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion on April 24, 2026, recommending authorization of Cenrifki (tolebrutinib) for adults with secondary progressive MS (SPMS) who have not relapsed in the prior two years ¹. A formal European Commission decision, which typically follows a CHMP opinion within roughly two months, is now pending.

The endorsement comes roughly four months after the U.S. Food and Drug Administration rejected the same drug, citing both an uncertain benefit-risk profile and the risk of severe or potentially fatal drug-induced liver injury (DILI) ². Sanofi said at the time that the FDA’s stance represented a “significant and meaningful change in direction” from earlier agency feedback.

Tolebrutinib sits in the BTK-inhibitor class, a group of drugs originally developed for oncology that pharma companies are now repositioning for autoimmune diseases. Rival Merck KGaA’s evobrutinib failed in late-stage MS trials, underscoring how difficult the pathway has been for the class in neurology ³. Sanofi itself also carries another approved BTK inhibitor, Wayrilz, for a different indication.

Clinical Data Driving the Decision

The CHMP recommendation rests primarily on the Phase 3 HERCULES study, in which tolebrutinib delayed the onset of six-month confirmed disability progression by 31% versus placebo (hazard ratio 0.69; 95% CI 0.55-0.88; p=0.0026) ⁴. Secondary analysis showed patients on tolebrutinib experienced a 38% reduction in new or enlarging T2 brain lesions per year compared with placebo ³.

The drug is an oral, brain-penetrant compound that targets smoldering neuroinflammation – the mechanism thought to drive the relentless disability accumulation that defines non-relapsing SPMS, a patient population with few approved options. Supporting data from the GEMINI 1 and GEMINI 2 Phase 3 relapsing-MS studies, published in The New England Journal of Medicine, also informed the CHMP’s review ¹.

Safety Overhang Remains a Key Risk

The CHMP acknowledged liver enzyme elevations as a meaningful safety signal but concluded the benefit-risk balance was favorable for this underserved population ². Sanofi said strict liver-monitoring protocols and prompt management of enzyme elevations are required to mitigate DILI risk – a condition it has flagged as an identified, not merely theoretical, hazard.

In its earlier U.S. filing, elevated liver enzymes above three times the upper limit of normal were observed in 4.1% of tolebrutinib patients versus 1.6% on placebo, with a small subset (0.5%) recording peak ALT increases exceeding 20 times the upper limit, all within the first 90 days of treatment ⁴. The divergence in how U.S. and EU regulators weighed this safety profile will be closely scrutinized by investors and competing BTK-inhibitor developers, including Roche, which is advancing fenebrutinib in relapsing MS.

Deal Valuation Implications

Sanofi acquired tolebrutinib through its $3.7 billion buyout of Principia Biopharma in 2020, a transaction that has yet to produce an approved product in its home U.S. market ². The company was forced to record an impairment charge of nearly €1.7 billion ($2 billion) after both the FDA rejection and the failure of the HERCULES companion PERSEUS trial in primary progressive MS ³.

An EU approval would open the drug to a large market of SPMS patients across 27 member states, offering a partial revenue recovery. Tolebrutinib has also received provisional authorization in the United Arab Emirates for the same indication, and regulatory reviews in additional markets are ongoing ³. Deal-focused investors may also note the parallel in pharma M&A strategy: large-cap acquirers paying multi-billion-dollar premiums for early-stage assets continue to face execution risk, a theme also visible in AbbVie‘s $10.9 billion bet on Apogee Therapeutics in the atopic dermatitis space.

Management Outlook

“Addressing disability progression remains one of the most significant unmet needs in MS care,” Sanofi said in its April 24 statement, noting that additional submissions for Cenrifki are currently under review with regulatory authorities worldwide ¹.

The company has not provided updated commercial guidance for Cenrifki pending final EC authorization, and has not indicated whether it plans to refile with the FDA or pursue an appeal of the January rejection. Investors should monitor any investor-day commentary for updated peak-sales assumptions tied to the EU launch.

Conclusion

A positive CHMP opinion moves Cenrifki meaningfully closer to its first major market approval, providing a tangible catalyst for Sanofi’s neurology franchise after a bruising run of regulatory setbacks. The FDA’s ongoing rejection keeps the largest single pharma market off the table for now, and the liver-safety monitoring requirements could limit commercial uptake even in Europe.

For investors tracking Sanofi (SNY / EURONEXT: SAN), the key near-term milestones are the formal European Commission authorization decision – expected within months – and any signal from management on a potential U.S. resubmission strategy.

Not investment advice. For informational purposes only.