Jeffrey Cohen, MD

“Another way their selectivity may help is that in patients with comorbidities—pre-existing heart disease, for example&mdash;we may feel somewhat more comfortable using these medications.”

While the approval of fingolimod (Gilenya; Novartis) almost a decade ago was welcomed as the first of its class for multiple sclerosis (MS), further research identified the need for more selective sphingosine-1-phosphate (S1P) modulators due to adverse event (AE) monitoring needs associated with fingolimod. Since its approval, 2 more agents—siponimod (Mayzent; Novartis) and ozanimod (Zeposia; Bristol Myers Squibb)&mdash;have entered the market and another&mdash;ponesimod (Janssen)&mdash;is currently before the 

One such advantage that these more selective agents offer is that they allow for easier use in patients with comorbidities, which can encompass a large percentage of the MS patient population. Jeffrey Cohen, MD, director, Mellen Center for MS Treatment and Research, Cleveland Clinic, noted that additionally, while it is not clear if there are advantages in improving symptoms associated with MS, such as fatigue, it does seem that these agents do not worsen them.

, Cohen explained how often these oral agents are turned to in the treatment of patients with MS, as well as what benefits these selective S1P modulators offer clinicians who utilize them as first- or second-line therapies.

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The director of the Mellen Center for MS Treatment and Research at Cleveland Clinic discussed the benefit that physicians and patients can be provided by highly selective S1P modulators in MS treatment.

Jeffrey Cohen, MD: The Advantages of More Selective S1P Modulators

“The hope was that by developing more selective S1P modulators, that we would maintain the efficacy of fingolimod but avoid some of the off-target adverse effects.”

Over the last few decades, the pipeline of therapies developed for multiple sclerosis (MS) treatment that have successfully navigated the path to regulatory approval. One such class of medications is the sphingosine-1-phosphate (S1P) modulators, the first member of which to be approved was fingolimod (Gilenya; Novartis), which doubled as the first oral agent for the disease.

Over the years, the continued study of fingolimod has allowed for the identification of the need for more selective agents, in part due to the cardiac monitoring of patients that is required with fingolimod. Since then, 2 more agents—siponimod (Mayzent; Novartis) and ozanimod (Zeposia; Bristol Myers Squibb)&mdash;have entered the market and another&mdash;ponesimod (Janssen)&mdash;is before the 

FDA in the form of a new drug application

, Jeffrey Cohen, MD, director, Mellen Center for MS Treatment and Research, Cleveland Clinic, explained how the class has been developed to this point, and offered a look at how the S1P modulator class differs in mechanism of action from the other available agents in the MS treatment arsenal. 

The director of the Mellen Center for MS Treatment and Research at Cleveland Clinic spoke to the development of the sphingosine-1-phosphate modulator class in MS treatment.

Jeffrey Cohen, MD: S1P Modulator Development in Multiple Sclerosis

“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.”

American Academy of Neurology (AAN) 2020 Annual Meeting

, data from a pooled analysis of the phase 3 ASCLEPIOS I and II trials of ofatumumab was set to be presented by a group of study authors including Jeffrey Cohen, MD, neurologist, Mellen Center for Multiple Sclerosis (MS) Treatment and Research, Cleveland Clinic.

The data suggest that the Novartis agent 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; 

 = .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; 

 <.001) and 68.8% (HR, 0.312; 95% CI, 0.114—0.859; 

 = .024), respectively, in comparison. Results were similar for 6-month CDP.

 connected virtually 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. Novartis expects to receive regulatory approval for ofatumumab in the US in June 2020 and in Europe by Q2 2021.

1. Montalban X, Cohen J, Comi G, et al. Ofatumumab Reduces Disability Progression Independent of Relapse Activity in Patients with Relapsing Multiple Sclerosis. 

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.

The neurologist at the Mellen Center for MS Treatment and Research at Cleveland Clinic spoke to the wide variety of clinical benefits observed with ofatumumab treatment and how it fits into the MS care landscape.

Jeffrey Cohen, MD: Ofatumumab's Potential Role in MS Care

“It was somewhat of a pleasant surprise that ofatumumab was of benefit in preventing disability worsening independent of its effect on relapses.”

In newly published comparative data, Novartis’ first fully human anti-CD20 monoclonal antibody, ofatumumab, was shown to be superior to teriflunomide (Aubagio; Sanofi) in its efficacy in treating patients with relapsing multiple sclerosis (MS).

The pooled analysis from the phase 3 ASCLEPIOS I and II trials and 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 in a single subgroup of patients. The data had been scheduled to be presented at the 

To find out more about what the clinical community can take away from these data, 

 connected virtually with study author Jeffrey Cohen, MD, neurologist, Mellen Center for MS Treatment and Research, Cleveland Clinic. In the interview, he detailed the findings of the analysis and shared his insight into what these data may suggest about ofatumumab’s potential to treat other forms of MS.

Montalban X, Cohen J, Comi G, et al. Ofatumumab Reduces Disability Progression Independent of Relapse Activity in Patients with Relapsing Multiple Sclerosis. 

The neurologist at the Mellen Center for MS Treatment and Research at Cleveland Clinic discussed the findings of a new pooled-data analysis of ofatumumab from the phase 3 ASCLEPIOS I and II trials.

Jeffrey Cohen, MD

Articles

Jeffrey Cohen, MD: The Advantages of More Selective S1P Modulators

Jeffrey Cohen, MD: S1P Modulator Development in Multiple Sclerosis

Jeffrey Cohen, MD: Ofatumumab's Potential Role in MS Care

Jeffrey Cohen, MD: The Success of Ofatumumab in Relapsing MS