Post hoc analysis shows that local inflammatory lesions associated with treatment with Sanofi’s Cenrifki (tolebrutinib) in patients with multiple sclerosis (MS) may not be a sign of failure.
In the pivotal Phase III HERCULES trial (NCT04411641) and GEMINI programme (NCT04410978 and NCT04410991), Cenrifki reduced the risk of confirmed disability accumulation (CDA) by 31% and 29% relative to placebo and teriflunomide in patients with non-relapsing secondary progressive MS (nrSPMS) and relapsing MS (RMS), respectively. During the poster presentation session “MS and Related Disorders 1”, Sanofi shared additional analysis on the relationship between new focal inflammatory lesions and the risk of disability accumulation.
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The post hoc analysis showed that the CDA risk was reduced in Cenrifki-treated patients irrespective of whether new focal inflammatory lesions were present or absent during the trials. Cenrifki reduced the CDA risk in patients who did not have new focal inflammatory lesions as well as among patients who developed new Gd+ T1 lesions or new/enlarging T2 lesions.
This data supports the mechanism of action of Cenrifki targeting chronic inflammation, which drives disability progression beyond acute inflammation. Furthermore, the analysis suggests that the development of new focal inflammatory lesions during treatment may not indicate treatment failure, as a disability benefit was observed in both those with and without new focal inflammatory lesions during the trial.
In clinical practice, the appearance of new Gd+ T1 lesions and new or enlarging T2 lesions has historically prompted clinicians to consider therapy modification or treatment escalation, especially in relapsing MS, as the new MRI activity signals recent active inflammation and a suboptimal response to the prescribed disease-modifying therapy. But Sanofi provides evidence that new focal inflammatory lesions during treatment should not automatically be interpreted as a lack of therapeutic effect for Cenrifki.
As such, new focal inflammatory lesions may not be the best standalone marker of whether a drug targeting progression is delivering its main clinical benefit on disability. The measure of paramagnetic rim lesions (PRLs), slowly expanding lesions (SELs), and accelerated brain atrophy are imaging biomarkers conducted using MRI that could be used to detect MS disease progression. Furthermore, the monitoring of disease progression could include a combination of clinical tests, blood biomarkers, and cerebrospinal fluid biomarkers, alongside the imaging biomarkers.
The data was presented on 27 June at the 12th Congress of the European Academy of Neurology (EAN) 2026.
On 23 June 2026, Cenrifki received approval in the European Union (EU) for the treatment of nrSPMS in patients who have not had relapses in the last two years. Cenrifki represents the first-in-class product targeting disability accumulation in patients with nrSPMS. With the launch of Cenrifki around the corner in the EU, Sanofi is actively diverging from the presence of new focal inflammatory lesions as an indicator of treatment failure for products targeting MS disability progression.
