FDA Delays Ruling on Novartis’ Relapsing Multiple Sclerosis Drug Arzerra

The approval process of Arzerra was delayed. 

Novartis will have to wait a little longer to see if the U.S. Food and Drug Administration (FDA) will greenlight Arzerra (ofatumumab) as a treatment for patients with relapsing multiple sclerosis (RMS).

On Tuesday, the FDA extended its review of the Supplemental Biologics License Application for Arzerra in this indication by three months. Regulatory action is now expected in September 2020, the company said. Novartis did not disclose any reason for the regulatory delay in its announcement.

The delay puts Novartis behind as other companies carve up the RMS market, including Bristol Myers Squibb which won approval for Zeposia (ozanimod) in RMS earlier this year and Roche’s Ocrevus, which earned nearly $4 billion in revenue last year.

Marie-France Tschudin, president of Novartis Pharmaceuticals, said the company will work with the FDA to complete the review of Arzerra as soon as possible.

“We are well prepared and ready to launch ofatumumab upon approval. We are committed to the MS community and look forward to bringing this important advancement to patients with MS,” Tschudin said in a statement.

Novartis submitted its sBLA based on results from the Phase III ASCLEPIOS I and II clinical trials, which compared Arzerra to Sanofi’s Aubagio (teriflunomide) in patients with relapsing forms of multiple sclerosis. The studies hit their primary endpoints as Arzerra demonstrated a highly significant and clinically meaningful decrease in the number of confirmed relapses. The trials also hit key secondary endpoints, delaying the time to confirmed disability progression.

Arzerra is a targeted B-cell therapy that, if approved, addresses a clinical unmet need as the first B-cell therapy for RMS patients that can be self-administered at home through an autoinjector pen. Arzerra 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, Novartis said. Arzerra was previously approved by the FDA to treat chronic lymphocytic leukemia.

Last week, Novartis released a post-hoc analysis of the Phase III studies that showed 47% and 87.8% of patients treated with Arzerra achieved no evidence of disease activity within the first and second year of treatment, respectively. A separate analysis from the APLIOS Phase II trial showed treatment with Arzerra 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, the company noted.

Additional regulatory filings are currently underway and regulatory approval for Arzerra in Europe is expected by mid-2021.

Novartis obtained rights for ofatumumab from GlaxoSmithKline in all indications, including RMS, in December 2015. The drug was originally developed by Genmab.