Lemtrada Denied FDA Approval; More Studies Needed

Genzyme Plans to Appeal the FDA’s Decision

Lemtrada™ (alemtuzumab, formerly Campath) did not receive approval from the United States Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis (MS). Genzyme, a Sanofi company, announced today that it had received a Complete Response Letter from the FDA, informing them that the application for their drug is “not ready for approval.”

The issue, according to the FDA, lies in the design of the Phase III studies. These compare the effectiveness and adverse effects of Lemtrada against one of the self-injected interferons (an approved disease-modifying therapy for MS). In most instances, rigorous drug trials compare an investigational treatment against a placebo, which is a treatment that appears similar to the investigational drug but has no active ingredients. By using a placebo in double-blind studies, neither the patients nor the doctors know who is receiving the active treatment and who is receiving the inactive placebo.

In the Lemtrada studies, patients and treating doctors were aware of which drug the patients were receiving, so it was “unblinded.” As explained below, this is due to the fact that very specific and different reactions to the two different drugs could occur. However, the evaluating doctors who reviewed the data were blinded. They did not know which treatment each patient was receiving.

Lemtrada is given in annual courses by intravenous (IV) infusion, and works by depleting the circulating lymphocytes (B and T cells). Lymphocytes are immune-system cells produced to fight infection and disease, and with MS, these cells are misdirected to cause damage to the nerves of the central nervous system (CNS) and the nerves’ protective covering (myelin). For the 12 months following the Lemtrada infusion, as these lymphocytes repopulate, they may be reprogrammed to be “less damaging” to myelin once these cells reappear. However, when the lymphocytes are initially depleted, 90 percent of individuals receiving Lemtrada develop a widespread rash – and blinding a patient or treating physician to this temporary side effect is problematic. Also, individuals taking interferons may often experience temporary flu-like symptoms, which are not seen with Lemtrada.

Although the Phase III trials showed that Lemtrada performed significantly better than the interferon it was compared to, the FDA needs to see stronger evidence from “adequate and well-controlled studies that demonstrate [that] the benefits of Lemtrada outweigh its serious adverse effects,” according to a press release from Genzyme. The release states that the “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 states that they “strongly disagree” with the FDA’s conclusions and plans to appeal the decision. Additionally, Genzyme President and CEO, David Meeker, MD noted that they are “extremely disappointed with the outcome of the review and the implications for patients in the U.S.”

As an MS neurologist and the Chief Medical Officer of MSAA, Dr. Jack Burks explains, “I support every effort to bring additional effective and safe treatments for our patients with MS. While additional FDA deliberations or reports about Lemtrada after the FDA Advisory Hearing are not available, Genzyme’s press release states that the FDA has requested more trial data utilizing a ‘different design and execution’ plan before they will consider approval of Lemtrada. Genzyme will appeal that FDA decision.

“For the MS patient, this means that Lemtrada will not be available in the United States until the FDA re-evaluates and approves it, either following an appeals process or after additional clinical trials. Lemtrada is already approved within the European Union, Canada, and Australia. These approvals were made from the same data that were submitted to the FDA for approval in the United States.”

Genzyme’s press release also notes that in addition to Lemtrada’s approval in the European Union, Canada, and Australia, additional marketing applications for Lemtrada are under review by regulatory agencies around the world. For more information, please see MSAA’s most recent article on Lemtrada, FDA Committee Recommends Lemtrada for Approval.

Written by Susan Wells Courtney
Reviewed by Jack Burks, MD, MSAA’s Chief Medical Officer