A first-ever quantification of the risks to multiple sclerosis and Crohn’s disease patients who take Biogen Inc. and Elan Corp. PLC’s Tysabri (natalizumab) of developing the deadly, incurable infection progressive multifocal leukoencephalopathy may, along with a newly approved diagnostic, help alleviate anxiety among patients and health care providers.

“We see the inclusion in the Tysabri label of the exact risk of developing PML while on Tysabri as a strong positive as it could even drive Tysabri use in [JC] virus-positive patients,” research analysts Guillaume Van Renterghem, Martin Wales and Ian Douglas-Pennant of UBS Limited wrote following a FDA drug safety communication noting that Tysabri’s label has been revised to incorporate the new risk figures.

PML is a rare disorder in which the myelin coating of some brain nerve fibers is damaged when the common and usually harmless JC virus attacks patients whose immune systems have been weakened. FDA says there are three factors that increase the risk for patients taking Tysabri: Longer treatment duration, especially beyond two years; prior treatment with an immunosuppressant (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil); and the presence of anti-JC virus antibodies.

FDA says the estimated incidence of PML for patients who test positive for anti-JC virus antibodies is as follows:

No Prior Immunosuppressant Use

Prior Immunosuppressant Use

Tysabri exposure 1-24 months

<>

2/1,000

Tysabri exposure 25-48 months

4/1,000

11/1,000

(Limited data are available for patients who have been taking Tysabri for more than four years.)

The analysts noted that a UBS survey among MS specialists conducted last June “suggested the perceived risk of patients developing PML on Tysabri is much higher than the revised label suggests. With a risk of (only) 2/1,000 for the first 24 months for JCV+ patients having received prior immunosuppressants, improving physician perception of Tysabri’s safety profile should drive increased market share.”

Biogen has acknowledged that many patients who tested positive for JCV stopped taking Tysabri, but that the majority remained and the potential for testing for the virus will generate “net adds” for the product, which had third quarter revenues of $393 million, up 28%, but a shade below the consensus projection among analysts ([A#00111031018]).

Another plus for the drug is that FDA approved Quest Diagnostics Inc.’s Stratify JCV Antibody ELISA test the same day as it issued the drug safety communication, further allowing health care providers to quantify the risks to patients.

Data Becoming Clearer

This is the third drug safety communication FDA has issued on the risk of PML in Tysabri patients. The label change was the product of an sBLA the sponsors filed in Dec. 22 regarding the antibody data, with a standard 10-month review timeline extended three months by the agency Also see "Tysabri Usage Restrictions Likely To Remain Stable As FDA Considers REMS Modifications" - Pink Sheet, 20 October, 2011..

As of Jan. 4, 201 cases of PML have been reported among approximately 96,582 patients treated with Tysabri worldwide, FDA says. Biogen Idec cited FDA’s Adverse Event Reporting System and other physician reports for the information that 116 cases have been diagnosed in the European Union (where the addition of the antibody information to the label was approved earlier than in the U.S.), 75 in the U.S. and 10 in the rest of the world, and that 42 of the 201 total cases have died.

FDA’s advice to health care providers includes testing patients before or during treatment if their antibody status is unknown; subjecting them to periodic retesting, as patients who test negative for anti-JCV antibodies may become newly infected or the test may have been wrong; assessing anti-JCV antibody status with an analytically and clinically validated immunoassay; having patients contact them with any symptoms suggestive of PML, and stopping treatment immediately at the first sign or symptom of PML.

“We are actively engaged in research designed to stratify the risk of PML,” Biogen Idec says. In the meantime, the drug has a Risk Evaluation and Mitigation Strategy that includes a special restricted distribution program called the TOUCH Prescribing Program, which limits the drug to prescribers, infusion centers and pharmacies associated with infusion centers registered with the program (in separate versions for MS and Crohn’s patients).

Tysabri’s PML Risk Quantified In Revised Label; Can Added Certainty Add Scripts?

More from United States

More from North America