Sanofi’s investigational BTK inhibitor tolebrutinib has demonstrated promising results in a phase 3 study of patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS), which the company said will “form the basis” for future discussions with global regulatory authorities.
The phase 3 HERCULES trial has been comparing an oral dose of the candidate to placebo in MS patients who have stopped experiencing confirmed relapses but continue to experience accumulation of disability.
Tolebrutinib met the primary endpoint of improvement over placebo in delaying time to onset of confirmed disability progression, and according to Sanofi, is now the first and only drug to show a reduction in disability accumulation in this patient population.
However, the company noted that the phase 3 GEMINI 1 and 2 trials of the drug in relapsing forms of the neurological disorder did not meet their shared primary endpoint of reducing annualised relapse rate compared to its current oral MS therapy Aubagio (teriflunomide).
An analysis of six-month data from the GEMINI studies showed there had been a “considerable delay” in time to onset, the company added.
Affecting approximately 2.9 million people worldwide, MS occurs when the immune system attacks the protective myelin sheath that covers the nerves and disrupts communication between the brain and the rest of the body.
Relapsing MS, characterised by attacks of worsening neurologic function followed by partial or complete recovery periods, accounts for about 85% of initial diagnoses, while nrSPMS is less common.
Houman Ashrafian, head of research and development at Sanofi, said: “Tolebrutinib represents an unprecedented breakthrough as a potential first-in-disease treatment option with clinically meaningful benefit in disability accumulation.
“Addressing disability accumulation, thought to be driven by smouldering neuroinflammation, remains the greatest unmet medical need in people with nrSPMS today.”
The results come just two months after Sanofi shared positive results from a mid-stage study of its investigational CD40L monoclonal antibody frexalimab in relapsing MS.
The candidate, which is already in phase 3 development for relapsing MS and nrSPMS, showed a significant reduction in plasma levels of neurofilament light chain, a key biomarker associated with MS nerve cell damage, after one year of treatment.