The neurologist at the Mellen Center for Multiple Sclerosis Treatment and Research at Cleveland Clinic discussed how the agent might fit into the treatment landscape if its sBLA is approved by the FDA later this year.
Jeffrey Cohen, MD
At the American Academy of Neurology (AAN) 2020 Annual Meeting, data from a pooled analysis of ofatumumab from the phase 3 ASCLEPIOS I and II trials were anticipated to be presented by a number of study investigators, including Jeffrey Cohen, MD, neurologist, Mellen Center for Multiple Sclerosis (MS) Treatment and Research, Cleveland Clinic.
Novartis’ first fully human anti-CD20 monoclonal antibody was shown to be superior to teriflunomide (Aubagio; Sanofi) in its efficacy in treating patients with relapsing MS. The data suggest that ofatumumab significantly reduced the risk of 3- and 6-month confirmed disability progression (CDP) compared to teriflunomide in all groups assessed save for 1 subgroup of patients. For 3-month CDP, patients in Subset A experienced a risk reduction of 41.3% (hazard ratio [HR], 0.587; 95% CI, 0.407—0.848; P = .004) compared to those treated with teriflunomide. Those in Subset B and Subset C reported risk reductions of 48.4% (HR, 0.516; 95% CI, 0.365—0.729; P <.001) and 68.8% (HR, 0.312; 95% CI, 0.114—0.859; P = .024), respectively, in comparison. Results were similar for 6-month CDP.1
NeurologyLive connected with Cohen to discuss the anti-CD20 agent and how it might fit into the MS treatment landscape. He shared his insight into what these data may suggest about ofatumumab and how its delivery method might make it stand apart from other agents. Notably, Novartis expects to receive regulatory approval for ofatumumab in the US in June 2020 and in Europe by mid-2021.2
Jeffrey Cohen, MD: For me, this abstract underscores the broad range of clinical benefits of ofatumumab—it reduces relapses, it reduces disability worsening, it reduces MRI lesion activity and brain atrophy worsening. The effect on disability, probably, is both an effect on focal lesion activity and on whatever the pathophysiology is that leads to gradual worsening.
The main thing is that it reinforces the benefit we've seen from the anti-CD20 strategies that appear to be a very effective way to treat MS. The main advantage of ofatumumab over the available anti-CD20s is that it's self-administered by the patient—they don't have to come into an infusion center. So, first of all, even before the COVID-19 pandemic, that was anticipated to reduce costs and to be somewhat more convenient for patients, as they don't have to take a day off from work. But with the pandemic, it's emphasized that advantage because that's one of our main concerns, bringing people into a medical facility. That would be the main way it would affect the landscape.
The ASCLEPIOS trials showed that ofatumumab was effective in reducing the number of acute relapses and MRI lesion activity in participants treated with ofatumumab as compared to those treated with teriflunomide. This abstract was presenting some additional analysis from that study, showing that the disability accumulation, which has 2 components: disability accumulation related to incomplete recovery from relapses, and then also gradual worsening—what we would call progression. Ofatumumab was effective in preventing both of those. Specifically, what was done in this analysis was to look at disability worsening independently of relapses.
I would say as far as surprising, I think the presumption was that since this was mostly a relapsing MS population, that most of the benefit on disability was due to the prevention of relapses, so I guess it was somewhat of a pleasant surprise that ofatumumab was of benefit in preventing disability worsening independent of its effect on relapses.
One of the questions in the MS field is, whether medications work both on the physiology that causes relapses and the—we think—somewhat different physiology that causes gradual worsening. This has relevance to whether a medication might be helpful in progressive MS where this gradual worsening is the more prominent feature. We didn't look at that directly in these trials because these were mostly relapsing patients, but it does suggest that ofatumumab may be of benefit in progressive MS, too, which would not be clearly surprising since ocrelizumab, a related medication, has been beneficial in a progressive population.
It's a little bit hard to predict what the FDA is going to do and what indication it's going to approve, but I suspect it will be for relapsing forms of MS, like the recent approvals of other medications. I don't know for sure, but I expect that Novartis will pursue a progressive MS study and also probably will pursue a pediatric MS study. Those would be sort of the logical next steps.
1. Montalban X, Cohen J, Comi G, et al. Ofatumumab Reduces Disability Progression Independent of Relapse Activity in Patients with Relapsing Multiple Sclerosis. Neurology. 2020;94 (15 Suppl). 1845.
2. Novartis announces FDA and EMA filing acceptance of ofatumumab, a novel B-cell therapy for patients with relapsing forms of multiple sclerosis (RMS) [news release]. Basel, Switzerland: Novartis. February 24, 2020. Accessed April 27, 2020. globenewswire.com/news-release/2020/02/24/1988939/0/en/Novartis-announces-FDA-and-EMA-filing-acceptance-of-ofatumumab-a-novel-B-cell-therapy-for-patients-with-relapsing-forms-of-multiple-sclerosis-RMS.html