Stephen L. Hauser, MD

“The rubber meets the road when our ideas are tested in the clinical area, and one would never have expected a primacy of B cells in the MS pathway were it not for the B-cell therapeutics.”

, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, a presentation was given that detailed the upcoming phase 3 assessment of fenebrutinib, an investigational Bruton Tyrosine Kinase (BTK) inhibitor, in both relapsing and primary progressive multiple sclerosis (MS). There will be 2 trials in relapsing disease and 1 in progressive, with 1:1 randomization and estimated enrollment of 734 patients in each of the relapsing MS trials and 946 in the primary progressive MS trial.

All 3 trials aim to assess the agent’s impact on disease progression, and thus will feature 12-week composite Confirmed Disability Progression (cCDP12) as a primary end point—the relapsing trials will also include annualized relapse rate as a co-primary end point. Assessment with cCDP12 requires at least an increase in Expanded Disability Status Score (EDSS) score of ≥1.0 point from a baseline score of ≤5.5 points, or a ≥0.5 point increase from a baseline score of >5.5 points; a 20% increase from baseline in time to complete the 9-Hole Peg Test; or a 20% increase from baseline in the Timed 25-Foot Walk Test.

, Stephen L. Hauser, MD, professor of neurology, and director, UCSF Weill Institute for Neurosciences, who presented the details of these trials, spoke to the driving theory behind BTK inhibition in MS, and how fenebrutinib may play a role as a particularly specific inhibitor, unlike other agents in its class.

REFERENCE
Hauser SL, Bar-Or A, Francis G, et al. Examination of fenebrutinib, a highly selective BTKi, on disease progression of multiple sclerosis. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0211.

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The director of the UCSF Weill Institute for Neuroscience spoke to the advantages of having agents that can be used across the spectrum of MS, and the role disease progression plays early on.

Stephen L. Hauser, MD: Fenebrutinib and BTK Inhibition in Progressive MS

“This new idea that progression in MS is present across the continuum [of disease], and is also more easily controlled earlier on, means that highly effective therapy as early as possible is a very reasonable clinical approach to patients.”

, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, a number of presentations were given highlighting agents that are approved for use in patients at a variety of disease stages, ranging from clinically isolated syndrome (CIS) to secondary progressive multiple sclerosis (MS). Although MS is a field that is well-equipped with therapeutic options, the advantages of having high-efficacy therapies that can be used at almost any point in disease are somewhat obvious.

One such agent is ofatumumab (Kesimpta; Novartis), which Stephen L. Hauser, MD, professor of neurology, and director, UCSF Weill Institute for Neurosciences, and colleagues presented data on. Those findings suggest that ofatumumab is superior to teriflunomide (Aubagio; Sanofi) in newly diagnosed, treatment-naïve patients with multiple sclerosis (MS) who have low absolute relapse rates, very low MRI lesion activity, and prolonged time to disability worsening.

These findings also bring up the ongoing debate around whether early intensive (or induction) therapy or escalation therapy strategies should be utilized for patients with MS. As Hauser pointed out to 

 in this interview, the improved understanding of the role disease progression plays in the process of disease has given hints that initial or early treatment with therapies such as ofatumumab may provide better benefit.

REFERENCE
Gartner J, Hauser S, Bar-Or A, et al. Benefit-risk of ofatumumab in treatment-naïve early relapsing multiple sclerosis patients. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0192

Stephen L. Hauser, MD: Increasing Understanding of Disease Progression in MS

“Many experts in the MS area feel—and it’s certainly my feeling—that we want to minimize or halt progression as early as possible, even at the beginning of disease when progression may be more difficult to detect by our routine methods of interrogation.”

Stephen L. Hauser, MD, and colleagues presented data at 

, the 8th Joint ECTRIMS-ACTRIMS meeting, September 11–13, 2020, suggesting that ofatumumab (Kesimpta; Novartis) is superior to teriflunomide (Aubagio; Sanofi) in newly diagnosed, treatment-naïve patients with multiple sclerosis (MS) who have low absolute relapse rates, very low MRI lesion activity, and prolonged time to disability worsening.

Notably, these findings were consistent with the overall study population of ASCLEPIOS I and II, the pivotal trials for the agent. All told, compared to patients on teriflunomide, ofatumumab reduced annualized relapse rates (ARR) by 50.3% (0.09 vs. 0.18; 

<.001). As well, 3-month Confirmed Disability Worsening (CDW) risk was reduced by 38% (10.1% vs 12.8%; 

= .065), and 6-month CDW risk was reduced by 46% (5.9% vs 10.4%; 

 = .044). Gadolinium-enhancing T1 lesions per scan were cut by 95.4% (0.02 vs 0.39: 

 <.001) and new/enlarging T2 lesions per year were lowered by 82.0% (0.86 vs 4.78, 

To find out more about these data and how they translate clinically for the physician community, 

 reached out to Hauser, who presented the data and is a professor of neurology at, and director of, the UCSF Weill Institute for Neuroscience.

REFERENCE
Gartner J, Hauser S, Bar-Or A, et al. Benefit-risk of ofatumumab in treatment-naïve early relapsing multiple sclerosis patients. Presented at MS Virtual 2020 Joint ECTRIMS-ACTRIMS meeting; September 11–13, 2020. Abstract P0192.

The director of the UCSF Weill Institute for Neuroscience offered his perspective on data presented at MS Virtual suggesting ofatumumab’s benefit in patients with MS who were treatment naïve.

Stephen L. Hauser, MD

Articles

Stephen L. Hauser, MD: Fenebrutinib and BTK Inhibition in Progressive MS

Stephen L. Hauser, MD: Increasing Understanding of Disease Progression in MS

Stephen L. Hauser, MD: Ofatumumab in Treatment-Naïve Patients With MS

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