FDA to Review EMD Serono’s New Request for Approval of Cladribine for Treating Relapsing MS

Seven years after it first denied the request, the U.S. Food and Drug Administration accepted for review EMD Serono’s resubmitted New Drug Application (NDA) for cladribine tablets (brand name Mavenclad) as a treatment for patients with relapsing forms of multiple sclerosis (MS).

The regulatory agency agreed EMD Serono’s new application was sufficiently complete, addressing all issues from a Complete Response Letter issued in 2011, including the drug’s safety profile.

Supported by clinical data collected from over 2,700 patients with up to 10 years of safety data, the resubmitted NDA will allow a thorough review of the safety risks and overall benefit-risk profile of the therapy.

This decision to review the NDA was based on results from the drug’s extensive development program, which included three Phase 3 clinical trials — CLARITY (NCT00213135), CLARITY Extension (NCT00641537), and ORACLE-MS (NCT00725985) — the Phase 2 ONWARD trial (NCT00436826), and the ongoing long-term study PREMIERE (NCT01013350).

“We are delighted the FDA has accepted cladribine tablets for filing,” Belén Garijo, member of the executive board and CEO of healthcare at Merck KGaA in Germany, said in a press release.

EMD Serono is the biopharmaceutical business in the U.S. and Canada of Merck KGaA, Darmstadt, Germany.

“Our goal is to offer cladribine tablets to patients and physicians in the U.S. as a new treatment paradigm for relapsing MS, and we look forward to working closely with the FDA throughout the review process,” Garijo added.

Cladribine tablets are currently available in 38 countries for use in MS under the trade name Mavenclad, including Canada, Europe, Australia, Argentina, Israel, and the United Arab Emirates.

Merck KGaA is planning to file additional marketing applications in other countries this year.

“Merck KGaA have placed themselves in a strong position in the MS market with the expected approval of Mavenclad in the U.S. within the next 12 months,” Rahael Maladwala, pharmaceutical analyst at GlobalData, said in another press release.

“The drug has demonstrated good efficacy, compared to other rival treatments, and while there are still a relatively higher incidence of adverse events compared to other drugs on the market, major safety concerns with the drug have been eased by studies carried out over the last five years,” Maladwala added.

Mavenclad was designed to target immune T-cell and B-cells that trigger relapsing MS without suppressing the entire immune system. It differs from most other oral MS therapies by its short treatment course, up to 20 days for over two years.

This is enough to “reset” the immune system and allow patients to benefit from its effects for up to four years without being continuously on medication.

The drug is an immune-reconstitution therapy and therefore “tries to get to the cause of MS,” Gavin Giovannoni, chair of neurology at Barts and The London School of Medicine and Dentistry, lead investigator of the CLARITY studies, said in a previous interview with Multiple Sclerosis News Today.

Despite the setbacks of the FDA’s previous refusal to review the NDA, Mavenclad’s demonstrated high clinical efficacy has led to a strong uptake in Europe since its approval in August 2017, Maladwala said.

“The company hopes that this uptake can be replicated in the U.S. and Mavenclad can establish itself as a key treatment for relapsing forms of MS,” he said.