BETHESDA, Md. _ An FDA advisory committee unanimouslyvoted Thursday to recommend that Genentech Inc.'s clot-dissolvingdrug tPA be approved for the emergency treatment of stroke,bringing the company one step closer to the end of its decade-longcrusade to expand its market and change the way doctors treat thecondition.
The vote came almost as an anticlimax after a day in which theFDA's Peripheral and Central Nervous System Drugs AdvisoryCommittee grilled a bevy of experts from the South San Francisco-based company on the benefits _ and risks _ of treating strokes withthe drug, sold as Activase.
Afterward, Genentech officials were jubilant. Bill Young, thecompany's executive vice president, said the recommendation isparticularly gratifying given the company's long and persistentstruggle to bring the drug to market. "We're very pleased," he said."Now we have an obligation to make sure this drug is properly usedand marketed." He said the company would work with FDA on suchcrucial details.
Activase, which sells for $2,000 a dose, has presented complexchallenges to researchers attempting to prove its value _ and topanelists trying to assess information that almost seemedcontradictory in arriving at its decision. The key question Thursday:Should you permit the sale of a drug that may mitigate the terribledamage of a stroke when its potential benefits are counter-balancedby a substantial risk of severe, life-threatening hemorrhage?
In making its decision, the committee had data from two studies. Onewas actually the second phase of a two-part study of 624 patientssponsored by the National Institute of Neurological Disorders andStroke (NINDS). It found that the drug clearly prevented severe braindamage when it was administered within three hours after strokebegins, compared with patients treated later or with placebo.
An earlier study of 620 patients given tPA within six hours of astroke _ the European Cooperative Acute Stroke Study _ had shownvery little benefit, and only on secondary measures of mental acuity.
The NINDS study, published last December in the New EnglandJournal of Medicine, found that patients treated with tPA were atleast 30 percent more likely to suffer minimal or no lasting disabilityfrom a stroke, measured at three months using four neurologicalassessment scales.
But by the end of the three months, 28 patients suffered intracerebralbleeding _ and 17 of those died. Six of the hemorrhages occurred inpatients treated within three hours, compared with just two in patientson placebo. The timing suggests the bleeding stemmed from tPAtreatment, according to the company's research findings.
Rather than recommend against approval of a drug that is perhaps theonly treatment for the cause of a stroke, the panelists suggested thatthe FDA and Genentech work to resolve safety concerns with acarefully crafted label that alerts physicians to the pitfalls oftreatment.
Sid Gilman, the panel's chairman and professor of neurology at theUniversity of Michigan Medical Center, in Ann Arbor, said, "Itstrikes me that the NINDS trial provided substantial evidence ofefficacy provided that treatment was initiated within three hours ofthe stroke, while the European study failed to show efficacy whentreatment was given four or five hours after stroke." Herecommended that the label reflect the urgency of treating withinthree hours of stroke.
Gilman also recommended that labeling should favor use of CTscanning, the primary diagnostic imaging tool, rather than magneticresonance. CT scanning is more widely available and can readilydetect blood, Gilman said, arguing the potential benefit outweighedthe risk of exposing the patient to ionizing radiation.
CT scanning would detect cerebral edema, or swelling, which seemsto increase the risk of hemorrhage. "The risk of hemorrhage isenough to rule out treatment if there's any edema," said DavidDrachman, a panelist and professor of neurology at the University ofMassachusetts Medical School, in Worcester.
John Hallenbeck, chief of the stroke branch at NINDS, in Bethesda, anon-voting consultant to the panel, advised the members not to be sostrict in its labeling guidelines that the contraindications "preclude aphysician's judgment."
Thomas Brott, director of the University of Cincinnati's StrokeResearch Center, said patients would fare better now that doctors willhave access to a drug that can spare them severe disability. "It's agreat day for stroke patients and the health professionals that treatthem," he said.
Genentech's stock (NYSE:GNE) closed the day down 12 cents to$52.87. n
-- Steve Sternberg Special To BioWorld Today
(c) 1997 American Health Consultants. All rights reserved.