Sanofi recently announced that its subsidiary Genzyme has received a Complete Response Letter from the US Food and Drug Administration (FDA) for its supplemental Biologics License Application seeking approval of Lemtrada (alemtuzumab) for the treatment of relapsing forms of multiple sclerosis.

A Complete Response Letter informs companies that an application is not ready for approval. FDA has taken the position that Genzyme has not submitted evidence from adequate and well-controlled studies that demonstrate the benefits of Lemtrada outweigh its serious adverse effects. Genzyme understands that the conclusion is related to the design of the completed phase III active comparator studies of Lemtrada in relapsing-remitting MS patients. FDA has also taken the position that one or more additional active comparator clinical trials of different design and execution are needed prior to the approval of Lemtrada.

Genzyme strongly disagrees with the FDA’s conclusions and plans to appeal the agency’s decision.

“We are extremely disappointed with the outcome of the review and the implications for patients in the US suffering with multiple sclerosis who remain in need of alternative therapies to manage a devastating disease,” said Genzyme president and CEO, David Meeker, MD. “We strongly believe that the clinical development programme, which was designed to demonstrate how Lemtrada compares against an active comparator as opposed to placebo, provides robust evidence of efficacy and a favourable benefit-risk profile. This evidence was also the basis for the approvals of Lemtrada by other regulatory agencies around the world.”

Lemtrada is approved in the European Union, Canada, and Australia, and  additional marketing applications for Lemtrada are under review by regulatory agencies around the world.

Sanofi does not anticipate that the CVR milestone of US approval of Lemtrada by March 31, 2014 will be met.

The Lemtrada clinical development programme included two pivotal randomized phase III studies comparing treatment with Lemtrada to Rebif (high-dose subcutaneous interferon beta-1a) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II), as well as an ongoing extension study. In CARE-MS I, Lemtrada was significantly more effective than Rebif at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.

Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.

Genzyme holds the worldwide rights to alemtuzumab and has primary responsibility for its development and commercialization in multiple sclerosis. Bayer HealthCare holds the right to co-promote alemtuzumab in MS in the United States. Upon commercialization, Bayer will receive contingent payments based on global sales revenue.

Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases.

Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs and has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, consumer healthcare, emerging markets, animal health and the new Genzyme.