ROCKVILLE, Md. _ An FDA advisory committee on Mondayunanimously approved an application from Hoffman-La Roche Inc.to expand the labeling for Roferon-A (Interferon-alpha-2a) to treatPhiladelphia chromosome positive chronic myelogenous leukemia(CML).

Citing Roferon's demonstrated ability to improve survival amongCML patients and "biological and clinical effects," several FDABiological Response Modifiers Committee members urged that FDAofficials revise the labeling to show the drug's benefits and risks as atreatment option for CML.

Some 20 percent of all leukemia cancer patients are diagnosed withCML. The standard chemotherapy regimen includes maintenancetherapy with Busulfan and Hydroxyurea.

Roferon is currently approved for treatment of hairy cell leukemiaand AIDS-related Kaposi's sarcoma. Roferon has been designated asan orphan drug for the treatment of CML, because only 2,500patients a year stricken with the disease.

Hoffman-La Roche, of Nutley, N.J., submitted an application lastApril for a product license application supplement citing twoEuropean studies and one U.S. clinical trial at M.D. Anderson CancerCenter, of Houston, showing improved outcomes with Roferoncompared to conventional chemotherapy.

Roferon increased survival rates by 15 months to 69 monthscompared to 54 months for conventional therapy. In addition, theM.D. Anderson study showed Roferon slowed disease progression.

However, data from the studies raised serious questions aboutadverse reactions and dosage. In two clinical studies the dosageregimen of Roferon resulted in substantial toxicity and prematurediscontinuation of therapy in some patients. While Hoffman-LaRoche termed the side effects "manageable," several committeemembers were concerned that Roferon resulted in significantly moreadverse events than conventional chemotherapy.

Some 80 percent of patients using Roferon reported constitutionalailments including weight loss and fatigue. Another 35 to 38 percentreported musculo-skeletal pain and gastrointestinal ailments. Adversereaction led to between 15 and 22 percent of patients withdrawingfrom therapy.

FDA officials noted that the Italian studies involved dosage levelsthat were less aggressive than typically used in the U.S.

To refine the dosing levels, the committee urged Hoffman-La Rocheto conduct additional studies on dose levels to determine if Roferonis more effective in patients who have not had prior treatment. M.D.Anderson investigators concluded that patients already treated for aperiod longer than one year would obtain only marginal benefits fromRoferon.

The manufacturer's recommended dose is 3 to 9 million internationalunits per day for the first week of treatment, followed by 9 millionInternational Units per day until a hematological response isachieved.

A Hoffman-La Roche investigator, John Goodman, Royal PostGraduate Medical School, Hammersmith Hospital, London, said theresults of two studies on dosage would soon by published in Lancet.

One advisory panel member asked why Roferon was approved in 43countries but not the U.S. Anthony Man, head of Hoffman-LaRoche's international oncology research team, said that the FDA'shandling of Hoffman-La Roche's application was "extremely fair"and that he had "no undue criticism."

"Internal priorities" not FDA regulatory issues determined that themanufacturer marketed the drug first in Europe and then decided toapply for sale in the U.S., he said. n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.

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