Following a partial hold on another lead candidate last year, Sanofi is reinvigorating its MS pipeline with a Phase II win for its investigational anti-CD40L antibody frexalimab.
Pictured: Sanofi sign in front of building/iStock, JHVEPhoto
Wednesday, Sanofi released data from a Phase II study showing its investigational anti-CD40L antibody frexalimab met the trial’s primary endpoint and significantly lowered disease activity in patients with relapsing multiple sclerosis.
After 12 weeks, patients treated with high and low doses of frexalimab saw an 89% and 79% reduction in the number of new gadolinium-enhancing (GdE) T1-lesions, respectively, compared with the placebo. At the 24-week follow-up, 96% of patients in the higher dose group did not show signs of new GdE T1-lesions.
Both frexalimab doses also decreased total GdE T1-lesions and new or enlarging T2-lesions.
As for safety, Sanofi found frexalimab to be generally well-tolerated.
Sanofi will present these findings during a late-breaking session at the 2023 Consortium of Multiple Sclerosis Centers annual meeting. The company will also push frexalimab into a pivotal trial in MS, which is expected to begin in 2024.
Frexalimab is an investigational monoclonal antibody that works by blocking the costimulatory CD40/CD40L pathway, which under healthy circumstances, is crucial for the activation and function of the adaptive and innate immune response. By inhibiting this pathway, frexalimab could address the underlying hyperactive autoimmune pathology of MS.
Sanofi’s candidate belongs to a class of medications that is promising in theory but has historically been held back by safety concerns. In the late 1990s, Biogen kicked off several clinical trials of its anti-CD40L antibody ruplizumab and a competing antibody, toralizumab, developed by Idec Pharmaceuticals.
Both were eventually discontinued due to thromboembolic side effects.
More recently, Novartis has also encountered difficulties with its CD40L blocker iscalimab. In September 2021, the investigational antibody failed to prove its superiority to tacrolimus at preventing organ rejection in kidney transplant recipients. The company was forced to terminate this trial.
A year later, in October 2022, Novartis axed another iscalimab trial in liver transplantation after the antibody had a worse benefit/risk profile than tacrolimus in these patients.
Sanofi Rallies in MS
Wednesday’s data drop comes nearly a year after the FDA put Sanofi’s other lead MS candidate, tolebrutinib, under partial clinical hold.
The regulatory order was triggered by documented cases of drug-induced liver injury in trial participants who had been treated with the candidate. According to Sanofi, patients who developed these liver injuries had underlying conditions that predisposed them to the complication, and discontinuing treatment would normalize liver injury biomarker levels.
Tolebrutinib is in a class of drugs that inhibit the BTK enzyme, an essential component in the B-cell development pathway. Targeting BTK could dampen the excessive activation of B-cells, which play a role in autoimmune diseases such as MS and myasthenia gravis.
In February 2023, after having its development suspended for months, Sanofi discontinued the development of tolebrutinib for myasthenia gravis. The drug remains under the FDA’s pause for MS.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com
