Novartis Reveals Positive Ofatumumab Data for Treating Relapsing Forms of Multiple sclerosis

By Pavel Ryzhov, Ph.D.

At the 6th Congress of the European Academy of Neurology (EAN) virtual meeting held last week, the biopharma giant released safety and efficacy data of Ofatumumab.

Multiple sclerosis (MS) is a complex disease. Its progressive, neurodegenerative, and autoimmune nature stemming from numerous genetic and environmental sources have been investigated for decades. It is now understood that MS is manifested by the immune response-driven demyelination of neurons in the central nervous system. This process leads to a gradual transition from mild to severe pathological outcomes, ranging from fatigue and blurry vision to epilepsy and paralysis.

Relapsing-Remitting Multiple Sclerosis (RRMS)

The most common MS type, RRMS, is characterized by a succession of new or increasing relapse attacks that are followed by partial or complete remissions. Therefore, disease-modifying interventions for RRMS have been an area of active pharmaceutical R&D progress, and the last three decades saw multiple treatments gaining regulatory approval and entering the market. However, their safety and long-term efficacy still present an unmet clinical need.

The hallmark of RRMS is the inflammatory lesions in the perivenular areas that, over time, ultimately lead to the irreversible oligodendrocyte damage. The infiltration of T-cells and B-cells in the lesions is the primary cause of this damage and accompanying demyelination. Therefore, dampening or otherwise influencing the inflammatory response by various immunosuppressants (IS) and immunomodulators (IM) has been a long-standing choice of treatment of MS in patients.

These include fingolimod, interferon beta, and other targeted therapies (against T- and B-cells), that limit the pool of immune cells, causing a reduction in lesions. Magnetic resonance imaging (MRI) is particularly useful in detecting these lesions in MS patients over time and serves in establishing prognosis and monitoring treatment progress. The lesions detected by MRI are classified as T1 and T2, based on the types of radiofrequency pulses used for imaging, with gadolinium (Gd+) being used as a contrasting agent for T1 lesion detection. No new MRI-detected lesions, together with the absence of relapses and lack of disability progression, form a surrogate biomarker combo, also known as no evidence of disease activity (NEDA-3).

Novartis’ Ofatumumab for RRMS

Novartis recently presented the post hoc analysis of the data from Phase II and Phase III studies, investigating human anti-CD20 monoclonal antibody ofatumumab as a self-administered monthly subcutaneous injection for the treatment of relapsing forms of MS [1]. According to the results from Phase II, ofatumumab, originally developed by Genmab, can bind to the distinct CD20 epitope, depleting B- and T-cell subsets, such as memory and naïve B-cells and activated T-cells.

The results from PHASE III ASCLEPIOS trials (double-blind, randomized, multi-center) further demonstrated that monthly ofatumumab injections had achieved NEDA-3 in year 1 and year 2 as compared to the standard of treatment, daily oral teriflunomide (47.0% vs. 24.5% and 87.8% vs. 48.2% in Y1 and Y2 respectively). Specifically, one of the NEDA-3 components, the annualized relapse rate, has been reduced in the ofatumumab arm by over 50% in both ASCLEPIOS I and II trials as compared to teriflunomide.

With respect to MRI-detected lesions, ofatumumab also demonstrated a reduction in both Gd+T1 and T2 lesion numbers (over 93% for Gd+T1 and over 82% in T2 respectively). Disease progression, as measured by 6-month disability worsening (CDW), has also been reduced by over 32% in ofatumumab arm as compared to the comparator. Finally, Novartis reported that patients have 3x higher chances of achieving NEDA-3 with ofatumumab treatment in the first year of therapy and 8x in the subsequent year, further marking its superior efficacy and tolerability.

Based on these results, Novartis has filed for the regulatory approval of ofatumumab as the first-in-line treatment for patients with relapsing forms of multiple sclerosis with the expected decision to be made in June 2020.

Related Article: Novartis’ Axial Spondyloarthritis Drug, Cosentyx Shines in Phase 3 Study

References

1. https://www.novartis.com/news/media-releases/novartis-announces-new-late-breaking-ofatumumab-data-ean-demonstrating-robust-efficacy-and-safety-treatment-relapsing-forms-multiple-sclerosis-rms
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099351/
3. https://onlinelibrary.wiley.com/doi/full/10.1111/ene.13819

Author

Pavel Ryzhov