Dr Stephen HauserStephen L. Hauser, MD
Novartis has announced positive results from the phase 3 ASCLEPIOS I and II studies of ofatumumab, in which the potent, fully-human antibody targeting CD20 positive B-cells demonstrated superiority in treating patients with relapsing multiple sclerosis (MS) versus teriflunomide (Aubagio; Sanofi).1

The investigational agent, also known as OMB157, was evaluated in a dose of 20 mg every 4 weeks against a 14-mg dose of teriflunomide. It showed clinically meaningful and significant reductions in annualized relapse rates. The top-line results are anticipated to be presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place September 11–13, 2019, in Stockholm, Sweden.

“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, 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 safety profile of the treatment was deemed to be favorable, with investigators making observations consistent with that of previous studies. Novartis is expecting to initiate regulatory submissions for ofatumumab by the end of 2019.

“Ofatumumab, if approved, could be a highly attractive treatment option for a broad RMS patient population, including early MS,” said John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis. “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 identical in design, lasting up to 30 months and including 1882 participants at more than 350 centers in 37 countries. All patients were required to have an Expanded Disability Status Scale (EDSS) score between 0 and 5.5, with the ability to walk short distances without aid.

Overall, ASCLEPIOS I included 927 patients and ASCLEPIOS II included 954. Baseline mean MS duration since first symptom was about 8 years, the mean EDSS score was 2.9, and about 40%  of patients had Gd+ lesions. In addition to both trials meeting their primary end point, the key secondary end points—delaying time to confirmed disability progression at 3 and 6 months—were also met. Additional secondary end points included confirmed disability improvement at 6 months, gadolinium-enhancing T1 lesions, number of new or enlarging T2 lesions, serum levels of neurofilament light chain (NfL), and rate of brain volume loss.

Ofatumumab is also being evaluated in a number of other studies. One, a long-term study (NCT03650114), includes a sub-study to determine the effects of the treatment on the development of antibody responses to certain vaccines and keyhole limpet hemocyanin (KLH) neo-antigen in subjects with relapsing MS. The others include NCT03249714, a phase 2 study which will assess the treatment versus placebo in a group of 60 participants in Japan; and NCT03560739, which is a 12-week, open-label, phase 2 study in 284 participants to test ofatumumab’s bioequivalence after week 8 between a pre-filled syringe and auto-injector.
REFERENCE
Novartis ofatumumab demonstrates superiority versus Aubagio® in two head-to-head Phase III multiple sclerosis studies [press release]. Basel, Switzerland: Novartis; Published August 30, 2019. novartis.com/news/media-releases/novartis-ofatumumab-demonstrates-superiority-versus-aubagio-two-head-head-phase-iii-multiple-sclerosis-studies. Accessed September 5, 2019.