BIOGEN TO SEEK FDA OK `WITHIN WEEKS' FORINTERFERON THERAPY AGAINST MULTIPLE SCLEROSIS

By David N. LeffScience Editor

CAMBRIDGE, Mass. _ Updating Phase III trial results of itsrecombinant interferon-beta for treating multiple sclerosis (MS),Biogen Inc.'s vice president of medical affairs, Irving Fox, said thathe hopes to translate clinical results within a year to improvedtherapy for patients.

Fox addressed some 350 attendees at the 1995 scientific symposiumof the Massachusetts Institute of Technology on Friday.

Earlier this month, Cambridge-based Biogen filed a MarketingAuthorization Application with the European Medicines EvaluationAgency to sell its interferon-b 1A drug, trademarked Avonex, in all15 member states of the European Union. (See BioWorld Today,May 5, 1995, p. 1.) "Within the next several weeks," the company'sdirector of medical research, John Allen, told BioWorld, "we willsubmit a U.S. product license application to the FDA's Center forBiologics Evaluation and Research."

As Fox addressed an audience here, University of Coloradoneuroradiologist Jack Simon told the annual Academy of Neurologymeeting in Seattle how he had used magnetic resonance imaging(MRI) to pinpoint and measure active and inactive lesions in thebrains of MS patients enrolled in the two-year, six-center Biogentrial.

Fox explained that the rare-earth metal, gadolinium, at the heart ofthe MRI scanner, "passes the blood-brain barrier and lights up areasof inflammation." He reported that in the trial's first year, whenpatient population totaled 301, evenly divided between 143 placeboand 158 interferon participants, the MRI data showed that annuallesion count dropped an average of 2.32 among the controls, but 3.17in the interferon cohort. In year two, he added, whenevaluable patient numbers totaled 174, the therapeutic drug groupaveraged 0.78, versus 1.6 for the placebo panel.

"That is," Fox summed up, "beta interferon decreased lesionnumbers, by MRI gadolinium scan, where the MS disease is _ in thebrain."

"From the clinical perspective," Allen said, "the most conclusive wayto capture the effect of therapy on MS disability, is to measure theprogression rate." He explained: "This primary endpoint of our trialmeasured the rate at which patients develop a one-point increase indisability. It decreased by approximately 40 percent more in theinterferon-beta-treated patients than in the placebo group."

There is no treatment for MS, only for its symptoms, Fox observed."These focus on management of complications; corticosteroid andadrenocorticotropin hormone against acute flare-ups; antispasmodicsfor muscle spasms; antibiotics for the infections that occur."

He added that although there are no therapeutics for the underlyingdisease, "azothiazine and cyclosporin are used, because there's reallynot much else available."

Interferon-beta, despite its recent validation for decreasing frequencyof exacerbations, "does nothing against the progression course ofMS," Fox said, "where people go on accumulating disability overtime, and then get severely disabled."

Allen, who runs the MS program at Biogen, added: "At two years, forexample, in the total patient population of 301, those in the placebogroup had progression rates averaging 34.9 percent, versus 21.9percent in interferon-treated groups. (See BioWorld Today for Oct.11, 1994; p. 1.)

Health To Death On A Scale Of Ten

Fox defined the primary endpoint as measuring the over-all level ofneurological impairment in MS patients on a scale of 10. Zeroindicates no disability; 10 is death _ from the disease itself or frominfection. The 301 patients entered in the trial all rated from 1 to 3.5upon enrollment _ fully able to walk, with mild to moderatedisabilities.

An MS sufferer can expect sudden flare-ups or exacerbations of thedisease. These new or worsening symptoms _ for example, loss ofvision, slurred speech, problems of memory and judgment, poorbalance or coordination, numbness _ may last days, weeks ormonths, and then subside. Most remissions, though, don't return allthe way to baseline, but ratchet up another notch of disability. Thus,over 15 years of on-again, off-again stealthily climbing ill effects,half of such relapsing/remitting patients have lost the ability to walk.

Comparing the annual frequency of flare-ups between control andinterferon cohorts, Fox reported the experience of 173 patients whocompleted the entire two-year course of once-a-week intramusculardrug or placebo:

Placebo Interferon

Number of patients 87.0 85.0

Average flare-ups per year 0.9 0.6

Zero flare-ups per year 26.5 % 38.5 %

Three or more 32.0 % 14.0 %

Asked about antibody reactions to the interferon regimen, Foxreplied, "We have observed 22 to 23 percent incidence of antibodyformation during the two-year trial period." To which he added,"Also, 4 to 5 percent in the placebo group. So when we look at thosepatients who have antibody titers above the placebo ones, it's about15 percent, which is low _ and generally of low titer. There is nodifference in rate of flare-ups, or progression of disease, with orwithout antibodies."

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