Copenhagen, Denmark-based Genmab A/S and its partner, Switzerland-based Novartis, announced positive results from their Phase III ASCLEPIOS I and II clinical trials. The trials compared their ofatumumab in a head-to-head study with Sanofi Genzyme’s Aubagio (teriflunomide) in patients with relapsing forms of multiple sclerosis (RMS).
The trials met the primary endpoints, with ofatumumab demonstrating a highly significant and clinically meaningful decrease in the number of confirmed relapses. The trials also hit key secondary endpoints, delaying the time to confirmed disability progression.
“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,” stated Jan van de Winkel, Genmab’s chief executive officer. “We look forward to feedback from regulatory authorities and to this exciting new phase in ofatumumab’s development.”
Novartis licensed the rights to develop and commercialize ofatumumab from Genmab. Novartis indicates it plans to submit the drug to regulatory authorities by the end of this year. The Swiss company already markets ofatumumab under the brand name Arzerra, only as an oncology medicine to treat chronic lymphocytic leukemia (CLL). However, last year it indicated it would only be available in the U.S. on a compassionate use basis.
It acquired the drug from GlaxoSmithKline in 2014 as part of a $16 billion asset swap and joint venture deal. The 2015 deal settled outstanding rights issues to the drug, while Genmab, dubbed the co-developer, continued to earn royalties from net sales.
The ASCLEPIOS trials studied the efficacy and safety of monthly subcutaneous injections of ofatumumab 20 mg compared to once daily oral Aubagio (14 mg) in adults with RMS. The two studies, I and II, are twin, identical design trials with flexible duration up to 30 months. They are both double-blind, randomized, multi-center Phase III studies. They enrolled 1,882 patients with RMS between the ages of 18 and 55 years who had an Expanded Disability Status Scale (EDSS) score between 0 and 5.5. They were run at over 350 locations in 37 countries.
The companies plan to present the data on September 13 at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) being held in Stockholm, Sweden.
Ofatumumab targets the CD20 molecule on the surface of B-cells, killing them. In leukemia, there are too many B-cells. In MS, B-cells become overactive and attack the patient’s nervous system.
In the CLL market, competition is fierce, with drugs like Roche’s Gaxyva (onibutuzumab) dominating, which is partly why Novartis is focusing on the drug’s MS potential. However, the MS market is a tough one as well, again with Roche. Roche’s Ocrevus (ocrelilzumab) hit blockbuster status since its U.S. Food and Drug Administration approval in 2017 for relapsing and primary progressive forms of MS.
“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,” stated Stephen L. Hauser, 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.”