Sanofi's Genzyme unit announced that the FDA issued a complete response letter regarding a filing seeking approval of Lemtrada (alemtuzumab) for the treatment of relapsing forms of multiple sclerosis. The agency determined that the company "has not submitted evidence from adequate and well-controlled studies that demonstrate the benefits of Lemtrada outweigh its serious adverse effects."
According to Genzyme, the FDA's conclusion relates to the design of the Phase III CARE-MS I and CARE-MS II trials, which compared Lemtrada to Merck KGaA's Rebif (interferon beta-1a) in patients with relapsing-remitting MS. The drugmaker added that the regulator "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 said it "strongly disagrees" with the FDA’s decision and plans to appeal. Sanofi spokesman Jack Cox noted that the company "does not believe further studies to evaluate the efficacy of Lemtrada are required," adding that the drugmaker is studying the FDA’s letter and considering further steps, including any appeal time frame.
Bryan Garnier analyst Eric Le Berrigaud commented "this was a big blow for Sanofi, as Lemtrada would have provided a significant growth engine for the company as early as 2014." Analysts had expected that the injectable therapy, which was approved in Europe in September and in Australia and Canada in December, could generate annual sales of $707 million by 2018. "The key question now is whether they will commit to financing new trials in a scenario in which they would be delayed by three years in entering a very crowded market in 2018 to 2019," Le Berrigaud remarked, adding "I'm not very optimistic about the appeal of the FDA decision."
Genzyme CEO David Meeker said "we are extremely disappointed with the outcome of the [FDA] review." He added "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." Meeker noted that "this evidence was also the basis for the approvals of Lemtrada by other regulatory agencies around the world."
In November, an FDA advisory panel voted 17-0 with one abstention recommending approval of Lemtrada for the treatment of relapsing MS, although the panel also voted 11-6 with one abstention that clinical studies of the drug were insufficient to assess its effectiveness. Previously, agency staff said in a report that the therapy's "multiple serious and potentially fatal safety issues" may outweigh its efficacy unless it demonstrated "substantial clinical benefit."
Sanofi gained Lemtrada via its $20.1-billion acquisition of Genzyme in 2011, with shareholders who hold a contingent value right (CVR) set to receive cash payments based on performance of the drug. However, Sanofi said Monday that it "does not anticipate" that the CVR milestone related to US clearance by March 31, 2014 will be met. Bayer has the right to co-promote Lemtrada in the US if approved.
"Genzyme's takeover was about catching up in biologics, having a greater footprint in the United States, and also largely for Lemtrada," said Le Berrigaud, adding "this is unquestionably a setback, as without a US market such a product doesn't have the same potential." However, Renaud Murail of Barclays Bourse suggested that the FDA complete response letter was not a surprise for investors who had already factored in the risk. "Genzyme remains Sanofi's gem and this is only a half-defeat," Murail remarked.
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