Monthly injections of ofatumumab led to more clinically meaningful reductions in relapse rates and delayed disability progression than did daily treatment with Aubagio (teriflunomide) tablets in people with relapsing forms of multiple sclerosis (MS), results from two Phase 3 trials showed.
Ofatumumab, formerly known as OMB157, is a potent, self-administered monoclonal antibody that targets the CD20 protein marker on immune B-cells to cause their depletion. Under the brand name Arzerra, ofatumumab is an approved infusion treatment for adults with chronic lymphocytic leukemia, a blood cancer that typically develops in B-cells. Novartis acquired the rights to develop and commercialize ofatumumab under a license from Genmab in 2015.
Topline results of the ASCLEPIOS I and II studies in MS will be presented on Sept. 13 at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), to be held in Stockholm. Novartis is planning to file requests with health authorities for ofatumumab as a relapsing MS treatment by the end of this year.
“Ofatumumab, if approved, could be a highly attractive treatment option for a broad [relapsing MS] patient population, including early MS,” John Tsai, Novartis’s head global drug development and chief medical officer, said in a press release. “The powerful study results are a reflection of our commitment to reimagine MS treatment at all stages of the disease.”
ASCLEPIOS I and II (NCT02792218 and NCT02792231) were head-to-head studies with identical design and lasting up to 30 months. Both were double-blind, multicenter comparisons of the safety and efficacy of ofatumumab, given as 20mg subcutaneous (under the skin) injections once each month, with Sanofi Genzyme’s Aubagio as a 14mg once daily oral tablet in adults with relapsing MS, both relapsing-remitting MS and secondary progressive MS.
The trials included 1,882 participants ages 18 to 55, and were conducted in more than 350 sites across 37 countries. To be included, patients had to have an Expanded Disability Status Scale score between 0 and 5.5, meaning that they were all still walking without aid for at least short distances.
Both trials met their primary goal, as treatment with ofatumumab showed a highly significant decrease in the number of confirmed relapses, analyzed as the annualized relapse rate. Key secondary goals of delaying time to confirmed disability progression at three and six months were also met.
“It is clear that early initiation of highly effective treatment for MS improves long-term outcomes, and there is a high need for potent, safe, and convenient therapy that can be used to treat MS from the start,” said Stephen L. Hauser, MD, director of the UCSF Weill Institute for Neurosciences. “The results from ASCLEPIOS are wonderful news for patients who would like to take an effective B-cell therapy with low requirement for monitoring, avoiding visits to an infusion center.”
The trials also showed that, at six months of treatment, patients give ofatumumab had fewer brain areas affected by active inflammation and disease activity, as well as fewer new or enlarging brain lesions, lesser brain volume loss, and lower blood levels of neurofilament light chain — a proposed MS biomarker.
Ofatumumab’s pharmacokinetic properties — its absorption, distribution, and metabolism in the body, and its elimination — were also assessed throughout the treatment period.
Both studies also showed a favorable safety profile for ofatumumab, in line with the observations from previous Phase 2 data.
“This data signifies a possible turning point for ofatumumab and provides support for our belief that it has the potential, if approved, to become the first subcutaneous B-cell therapy for relapsing MS that can be self-administered by patients at home,” Jan van de Winkel, PhD, Genmab’s CEO, said in a separate press release. “We look forward to feedback from regulatory authorities and to this exciting next phase.”