Author Topic: New MS drug option--Lemtrada (alemtuzumab) gets FDA approval for sale in US  (Read 218 times)

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Offline agate

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Another new MS drug will soon be available in the US. Lemtrada (alemtuzumab) has received FDA approval for marketing in the US. It's not cheap, and I'm not sure how it can be determined that the drug has been so effective that a patient can stop taking it after two years. Since RRMS can reappear at any time in a patient who is in remission, how can anyone be sure that Lemtrada has been effective enough to stop taking it?  ???

From the Boston Globe, November 15, 2014:

Quote
In reversal, FDA approves Genzyme’s bid to sell MS drug in US

by Robert Weisman, Globe staff

Eleven months after rejecting a powerful multiple sclerosis drug considered key to the future of Cambridge biotech Genzyme, federal regulators Friday reversed themselves and approved sale of the medicine, called Lemtrada.

The Food and Drug Administration decision came after MS patients across the country called for more treatment options and Genzyme submitted a new analysis of clinical data to address FDA concerns about how the company had designed trials to test the drug’s safety and effectiveness.


Patients have been anxiously awaiting the ruling on Lemtrada because studies showed people using it suffered fewer flareups of the potentially debilitating autoimmune disease, and about 70 percent of them were able to stop taking the injectable drug after two treatment courses.

“This is a great day for the MS community,” said Melissa J. Burdick, an MS patient from Waterford, Conn., who lodged one of several citizen petitions with the FDA after it refused to approve Lemtrada last December. “I’m absolutely thrilled beyond words to have this choice. Many people, including me, have wanted another treatment option.”

The company announced the FDA approval at about 9 p.m. Friday.

Genzyme executives said Lemtrada will be priced at $158,000 for two courses of treatment over two years. Rebif, a competing drug compared with Lemtrada in clinical studies, costs $134,600 for a similar treatment regimen, or 17 percent less. But the Genzyme executives pointed out that patients on Lemtrada suffered 50 percent fewer relapses than those taking the other drug.

Lemtrada’s approval is a vindication of French drug maker Sanofi SA’s move to buy Genzyme for $20.1 billion in 2011. Former Sanofi chief executive Christopher A. Viehbacher sealed the deal by creating a new stock that would reward Genzyme shareholders if the MS drug was approved by regulators and met sales milestones.

Viehbacher, however, did not last long enough to savor the success; last month he was fired by Sanofi’s board, which was critical of his management style. Despite his departure, the Paris-based company has said it remains committed to Genzyme and Lemtrada.

While the drug already has been approved in more than 40 countries — including European Union nations, Canada, Mexico, Australia, and South Korea — the United States is the world’s largest drug market.

“This is a very significant event for us,” said Bill Sibold, senior vice president and head of the MS business at Genzyme, which won FDA approval for its first MS therapy, Aubagio, in 2012. “About 60 percent of the global market for multiple sclerosis is in the US. We talk about our aspirations to be leaders in MS. Up until this point, we’ve had Aubagio, which we’re very proud of. But this will give us both products for our US franchise.”

... In the United States, the company said Friday, the use of Lemtrada would “generally be reserved” for patients who have previously taken two or more other MS drugs but are still having relapses.

Aubagio, a pill, was Genzyme’s first approved drug outside the field of enzyme replacement treatments for rare genetic disorders such as Gaucher and Fabry diseases. Sanofi recently reported worldwide sales for Aubagio totaled $378 million year for the first nine months of 2014, while revenue from Lemtrada, which has launched in only 10 countries, totaled $18 million.

But industry analysts have projected Lemtrada has the potential to become a “blockbuster” drug, generating annual revenue of more than $1 billion.

Unlike Aubagio, Lemtrada is administered at hospitals and clinics through infusions that take about four hours. Patients undergo the treatment for five consecutive days in the first course of therapy, and then for three consecutive days 12 months later. The drug showed “sustained efficacy” after three years for about 70 percent of patients, according to clinical studies, meaning they didn’t have [to] take additional drug courses.

FDA regulators last year objected to Genzyme’s clinical trial design because patients knew whether they were taking Lemtrada or Rebif, a drug marketed by the Rockland biotech firm EMD Serono, but those assessing the trial data didn’t know. The regulators said they would have preferred a “double-blind” trial in which neither patients nor raters knew which drugs were being taken by individual patients.

Genzyme and patient advocates argued the side effects from the competing drugs were so distinct that it would be difficult, if not impossible, to conceal the identity of the treatments from patients in the trial. In resubmitting its application in May, the company provided additional materials sought by the FDA and a fresh analysis of the data to address concerns.

When it launches its second MS drug, Genzyme will boost its standing as an emerging rival to the leading MS drug maker, Biogen Idec Inc., which is based a few blocks from Genzyme in Cambridge’s Kendall Square.

Genzyme last week said it had begun enrolling patients in a clinical trial for a third MS drug candidate, a monoclonal antibody called VLA-2.

The entire article can be seen here.
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SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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MS Speaks--online for 12 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

Offline agate

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Alemtuzumab (Lemtrada) clinical trials reviewed
« Reply #2 on: November 17, 2014, 03:49:55 pm »
Journal Watch (November 16, 2014) also has an article on this new option but it is mainly a summary of the Boston Globe article. It refers to an article in the New England Journal of Medicine in 2012, providing information on clinical trial results along with a comment:

Quote
December 4, 2012

Pivotal Trials of Alemtuzumab in MS

Samia J. Khoury, MD reviewing Cohen JA et al. Lancet 2012 Nov 24. Coles AJ et al. Lancet 2012 Nov 24.

Two randomized trials provide evidence on alemtuzumab's efficacy and safety in treating multiple sclerosis — one in treatment-naive patients, the other in patients who relapsed on standard treatment.

Alemtuzumab is a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes. It is FDA approved for treatment of B-cell leukemia but not for treatment of multiple sclerosis (MS). Researchers conducted two multicenter, phase III, manufacturer-funded, 2-year trials of alemtuzumab to treat early relapsing–remitting MS.

In the trial by Cohen and colleagues, the investigators randomized 581 treatment-naive patients in a 2:1 ratio to intravenous alemtuzumab (12 mg daily for 5 days at baseline, then daily for 3 days at 12 months) or subcutaneous interferon beta-1a (IFNβ-1a; 44 μg 3 times per week). Coprimary endpoints were relapse rate and time to 6-month sustained accumulation of disability. Relapses occurred in 22% of the alemtuzumab group versus 40% of the IFNβ-1a group (P<0.0001), a 54.9% improvement. Sustained disability accumulation occurred in 8% of the alemtuzumab group versus 11% of the IFNβ-1a group (hazard ratio, 0.70). Most alemtuzumab recipients (90%) had infusion-associated reactions, 3% of which were serious. Thyroid-associated adverse events occurred in 18% of alemtuzumab recipients and immune thrombocytopenia in 1%. Two alemtuzumab recipients developed thyroid papillary carcinoma. One patient died after discontinuing corticosteroids for presumed autoimmune pancytopenia.

The trial conducted by Coles and colleagues included 840 patients with at least one relapse with interferon beta or glatiramer therapy, who were randomized 1:2:2 to receive 44 μg of subcutaneous IFNβ-1a, 12 mg of intravenous alemtuzumab, or 24 mg of alemtuzumab, following the same regimen as in the first trial, with the same coprimary endpoints. The 24-mg alemtuzumab group stopped recruitment mid-study to increase recruitment in the 12-mg group; outcomes are reported only for the 12-mg group. Relapses occurred in 35% of the alemtuzumab group versus 51% of the IFNβ-1a group (P<0.0001), a 49.4% improvement. Sustained disability accumulation occurred in 13% of the alemtuzumab group versus 20% of the IFNβ-1a group (HR, 0.58). The rate of infusion-associated reactions was 90% among the alemtuzumab recipients, and 77% had infections (mostly mild-to-moderate) compared with 66% in the IFNβ-1a group. Thyroid disorders occurred in 16% of alemtuzumab recipients and immune thrombocytopenia in 1%.

COMMENT

The findings of these two phase III trials confirm the previously reported beneficial effects of alemtuzumab against an active comparator. Alemtuzumab is the only drug shown to have superiority over IFNβ-1a in disability outcomes in a monotherapy phase III trial. However, the effectiveness comes at the price of increased autoimmunity during immune reconstitution. The significant risk for autoimmunity and the high rate of infusion-related reactions decrease the attractiveness of alemtuzumab for treatment-naive patients. It would likely be prescribed for patients with active disease who have failed interferon or glatiramer acetate therapy, especially those who are JC virus antibody–positive (and therefore at increased risk for progressive multifocal leukoencephalopathy from natalizumab; JW Neurol May 29 2012).

__________________

Dr. Khoury is the Jack, Sadie, and David Breakstone Professor of Neurology, Harvard Medical School, and Co-Director of the Partners MS Center, Brigham and Women's Hospital, Boston.

- See more at: http://www.jwatch.org/jn201212040000001/2012/12/04/pivotal-trials-alemtuzumab-ms#sthash.06PlclrW.dpuf
MS Speaks--online for 12 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.