Novartis Announces New Ofatumumab Data at EAN

Novartis announced new ofatumumab data from the Phase III ASCLEPIOS trials and the Phase II APLIOS trial were presented virtually at the 6th Congress of the European Academy of Neurology (EAN). The data continue to demonstrate ofatumumab (OMB157) as a potential novel treatment option for patients with RMS. The safety profile was comparable to teriflunomide.

Ofatumumab is a targeted B-cell therapy that, if approved, addresses a clinical unmet need as the first B-cell therapy that can be self-administered at home through an autoinjector pen. In addition to being presented virtually, the data were also published in the European Journal of Neurology, Volume 27, Supplement 1, May 2020.

A post hoc analysis from the Phase III ASCLEPIOS I and II trials (n=1882) assessed the odds of patients achieving NEDA-3 with ofatumumab versus teriflunomide within the first (Month 0–12) and second year (Month 12–24) of treatment. NEDA-3 is a comprehensive composite measure commonly used to assess treatment outcomes in patients with RMS. It is defined as an absence of three measures of disease activity: relapses; disease progression, measured as 6-month confirmed disability worsening (CDW), and gadolinium enhancing (Gd+) T1 lesions. The study results showed that compared with teriflunomide, a greater proportion of patients treated with ofatumumab achieved NEDA-3 in year 1 (47.0% vs 24.5%; P<.001) and in year 2 (87.8% vs 48.2%; P<.001).

“Achieving no evidence of disease activity is widely recognized as an important treatment goal for multiple sclerosis therapies,” said Professor Ludwig Kappos, University Hospital Basel. “These data suggest that halting new disease activity is possible by targeted B-cell therapy in RMS.”

A separate analysis from the APLIOS trial (n=284) showed ofatumumab treatment led to rapid and sustained depletion of both CD20+ B- and T-cells in patients with RMS. Ofatumumab depleted different B- and T-cell subsets including memory B-cells and naïve B-cells, as well as a subset of T-cells that are known to exhibit an activated phenotype. However, CD3+ T-cells that do not express the CD20 receptor, were largely unaffected.

“These results are encouraging and support our belief that, if approved, ofatumumab could have the potential to significantly improve the lives of people with RMS,” said Krishnan Ramanathan, Neuroscience Global Program Head at Novartis. “These data are a testament to our commitment to reimagining medicine and advancing innovative treatments that help people with this serious and progressive disease.”

Regulatory action for ofatumumab in the US is expected in June 2020.

Ofatumumab (OMB157) is a fully human anti-CD20 monoclonal antibody (mAb) in development for RMS that is self-adminstered by a once-monthly injection, delivered subcutaneously As shown in preclinical studies, ofatumumab is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion. The selective mechanism of action and subcutaneous administration of ofatumumab allows precise delivery to the lymph nodes, where B-cell depletion in MS is needed, and may preserve the B-cells in the spleen, as shown in preclinical studies. Once-monthly dosing of ofatumumab also allows fast repletion of B-cells and offers more flexibility. Ofatumumab was originated by Genmab and licensed to GlaxoSmithKline; Novartis obtained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, in December 2015.