Research News
Tysabri Returns to Marketplace
On June 5, 2006, the United States Food and Drug Administration (FDA) approved Tysabri® (natalizumab) to return to the marketplace for relapsing forms of MS. This is the sixth drug approved for the long-term treatment of multiple sclerosis (MS) in the United States.
Tysabri has been approved as a monotherapy, which means that it should not be combined with any other drug designed to modify or suppress the immune system. The distribution of Tysabri will be regulated by a Risk Management Plan known as the TOUCH (Tysabri Outreach: Unified Commitment to Health) Prescribing Program.
The TOUCH Prescribing Program is directed to prescribers (physicians), infusion centers, pharmacies, and patients considering Tysabri. Among others, it includes several documents that provide information, guidelines, checklists, and authorizations, as well as forms for enrollment, questionnaires, and status reports. Infusion center and pharmacy staff will be trained by the drug companies.
Marketed by Biogen Idec and Elan Corporation, Tysabri is the first humanized monoclonal antibody to be approved for the treatment of MS. It works by inhibiting the action of adhesion molecules on the surface of immune cells, and therefore prevents damaging immune cells from crossing the blood-brain barrier from the bloodstream and entering the brain and spinal cord. Tysabri is administered via intravenous infusions every four weeks in a TOUCH Program infusion center.
Tysabri had received early approval in November 2004, but was voluntarily taken off of the market in February 2005 after two people were found to have developed progressive multifocal leukoencephalopathy (PML), which is an often-fatal viral infection of the brain. A third person was later diagnosed with PML. Of these three individuals, two of the patients died; the third survived but is disabled. No other cases of PML have been found to be associated with Tysabri.
MSAA President and CEO Douglas G. Franklin represented MSAA at the FDA's Advisory Committee Meeting held in March 2006 to discuss Tysabri's effectiveness versus the potential for serious adverse events. At this meeting, Mr. Franklin advocated for the safety measures recommended by the FDA's Advisory Committee.
Mr. Franklin states, "While safety must be a primary consideration, MSAA enthusiastically supports the development of new medications to treat MS. Everyone associated with MSAA is extremely pleased to see Tysabri's return to the marketplace, along with the addition of the TOUCH Prescribing Program, which has been designed to closely monitor the safety of this new treatment. We look forward to the positive results of this treatment for those who may benefit."
Dr. Jack Burks, vice president and chief medical officer for MSAA, commented on the FDA's re-approval of Tysabri. "I am excited that the massive efforts in MS research have produced another drug, Tysabri, for the long-term treatment of MS. This drug is extremely effective in preventing inflammatory cells from entering the brain and damaging the myelin that insulates nerve cells."
Dr. Burks continues, "I welcome the opportunity to have this drug available for patients who are not responding adequately to current therapies, or who have intolerable side effects from those therapies. The pharmaceutical companies' Risk Management Plan called the 'TOUCH Prescribing Program' is a laudable effort to attempt to minimize the potential risk of PML - a rare but often fatal viral infection of the brain which has been associated with Tysabri.
"The requirements of the TOUCH Prescribing Program emphasize the cautious approach designed to balance the significant Tysabri benefits versus the potential serious adverse effects, which include death. I agree with the comments of Dr. Russell Katz, who serves as director of the FDA office that regulates drugs for neurological diseases. In a New York Times article, 'MS Drug Can Return, With Limits' (dated June 6, 2006), when asked about Tysabri's association with PML, Dr. Katz was quoted to have said, 'Yes, we expect there to be additional cases [of PML] and probably additional deaths as well.' Dr. Katz also notes that the risk is balanced by considerable benefits of the drug."
Dr. Burks concludes, "At this time, we cannot predict, prevent, treat, or cure PML. But as we proceed with great caution in an attempt to minimize this risk, the re-approval of Tysabri presents hope to a portion of individuals with MS. Many participants in the trial experienced very positive results, which includes slowing the progression of the disease."
The marketing of Tysabri resumes after a series of actions surrounding its availability. To follow is a timeline of these related events.
November 2004: The FDA granted accelerated approval for Tysabri based on one-year data from its two ongoing, two-year phase III trials. The one-year data for Tysabri showed a 66 percent reduction in relapses compared to those on placebo (in the AFFIRM monotherapy trial) and a 54 percent relative reduction in relapses for those taking Tysabri in combination with Avonex®, as compared with those taking Avonex plus placebo (in the SENTINEL add-on trial). Avonex is an interferon given weekly, one of the five other approved long-term treatments for MS.
February 2005: Tysabri was withdrawn from the marketplace by the manufacturer after two patients were found to have developed progressive multifocal leukoencephalopathy (PML), which is an often-fatal viral infection of the brain. These two patients who developed PML had been given the combination of Tysabri along with Avonex in an MS trial for more than two years. Based on the discovery of PML in these two patients who were given Tysabri, the FDA placed a hold on clinical trials using this drug. (A third patient who had been treated with Tysabri earlier in an open-label Crohn's disease clinical trial and died, was diagnosed with PML postmortem.)
February through August 2005: Biogen Idec (Tysabri's manufacturer) and Elan Pharmaceuticals (Tysabri's distributor) conducted an extensive evaluation of all patients treated with Tysabri in clinical trials for multiple sclerosis, Crohn's disease (an inflammatory disease of the small intestine and colon), and rheumatoid arthritis. The pharmaceutical companies reported that no cases of PML occurred in patients treated only with Avonex.
August 2005: Biogen Idec and Elan announced that no new confirmed cases of PML had been discovered. Nearly 2,000 MS patients from clinical trials participated in the safety evaluation.
February 2006: The FDA allowed a clinical trial of Tysabri to resume following the confirmation of no additional cases of PML.
March 2006: The FDA's Peripheral and Central Nervous System Drugs Advisory Committee Meeting was held; members of the Committee decided that Tysabri's effectiveness outweighs the potential for serious adverse events, recommending its return to the marketplace for treating individuals with the relapsing-remitting form of multiple sclerosis (MS).
June 2006: The FDA approved an application for Tysabri to return to the marketplace. The drug's distribution is limited to those who qualify for, register with, and follow the strict guidelines of a special distribution program known as the TOUCH Prescribing Program.
For More Information
For further information on Tysabri, health care professionals and patients may visit the FDA's website at: www.fda.gov/cder/drug/infopage/natalizumab/default.htm.
Readers may also go to MSAA's website at www.msaa.com to view earlier news articles about Tysabri. Website visitors may click on MSAA's publications to view the Spring 2005 issue of The Motivator, which contains a more scientific article in "Research News" on Tysabri and how it works.
Readers without internet access may contact MSAA at (800) 532-7667 to request a copy of the article.
By Susan Wells Courtney
Reviewed by Dr. Jack Burks
