SAN FRANCISCO _ Biogen Inc.'s clinical trial data onrecombinant interferon beta for treating multiple sclerosis havelived up to expectations. First and foremost, interferon betaadministration is able to significantly delay progress of thedisability associated with this neurological disease.According to principal investigator Lawrence Jacobs, of the StateUniversity of New York at Buffalo, this is the first drug that hasbeen demonstrated to actually affect the quality of life for patientswith multiple sclerosis."This is the first time we have an effective therapy for multiplesclerosis," Jacobs said.In Biogen's trial, which was supported by the National Institutes ofHealth, 301 patients with active relapsing multiple sclerosis wererandomly assigned to receive interferon beta or placebo. The studywas designed to measure disability outcome rather than relapse rate,including proportion of those individuals who remain free ofexacerbations _ periods of neurological dysfunction lasting morethan one day, extent of upper and lower extremity disability, changein brain plaque load on magnetic resonance imaging (MRI), whichcan detect lesions in the myelin sheath, and neuropsychologicalfunction.The patients in this study had scores of one to three and one-half onthe Expanded Disability Status Scale (EDSS), which measures andsums functional physiological systems. Researchers defined time toprogression in disability as an increase in EDSS score of one unitabove baseline persisting for at least six months.Speaking Monday afternoon at the annual meeting of the AmericanNeurological Association here, Jacobs explained that the mediantime to progression was three years in patients who receivedplacebo, and just above five years in patients who received once-weekly intramuscular injections of interferon beta. The data weresignificant at p = 0.03.Also, the therapy regimen decreased the one- and two-yearprogression rates by close to 40 percent. At the end of one year oftreatment, 20.1 percent of placebo-treated patients had progressedby 1 EDSS unit compared to 12 percent of patients on interferonbeta. At two years, the numbers were 36.3 percent for placebo and22.6 percent for treated patients. Patients receiving interferon betahad a significantly reduced rate of relapse as well by 31 percent(0.62 disease flare-ups per year as compared to 0.9 in the placebogroup; p = 0.003). Furthermore, MRI scans of treated patientsshowed a decrease in the number of lesions as well as their volume.The side effects were minor, Jacobs said.The relapsing kind of multiple sclerosis affects 75,000 to 140,000Americans. In all, some 250,000 to 350,000 Americans have thedisease. People with relapsing multiple sclerosis suffer bouts ofsymptoms, including fatigue, impaired vision, loss of balance andcoordination, slurred speech, tremors and partial or completeparalysis. Patients recover at least partially during the weeks ormonths after each episode but become progressively disabled.Stock Soared Since July, Dipped On MondayBiogen's stock (NASDAQ:BGEN) has been rocketing skywardever since July 26, when the Cambridge, Mass. company firstannounced that its recombinant interferon beta had achievedstatistically significant results in the Phase III multiple sclerosistrials. The announcement was unexpected, and the stock soared 50percent _ from $29.50 to $44.75 _ on heavy volume of 10 millionshares the day after. Since that time, it has climbed as high as$71.75 (on Sept. 28). Monday's news of the trial results came afterthe market closed and Biogen's stock closed at $52, down $2.75.The market was apparently caught by surprise in July because manyanalysts had discounted Biogen's chances of success with its drug.And at one time Biogen had claimed that it wasn't expecting resultsfrom the trial until sometime in 1995. However, in January, CEOJames Vincent told attendees at the annual Hambrecht & Quist LifeSciences Conference in San Francisco that patient dosing in the trialwas almost complete and that his company was expecting to reportthe trial results in the second half of 1994.Trading in Biogen's stock was frenzied on Friday, as well _ andnot just because of optimistic anticipation of the clinical trial resultspresented here Monday. More than 6.3 million shares of Biogen'sstock traded hands Friday, and the stock closed at $54.75, up $5.50from the previous day, fueled by rumors that Schering-PloughCorp. is interested not only in marketing Biogen's interferon betabut also in possibly acquiring Biogen outright. Schering-Ploughalready markets Biogen's Intron A alpha interferon as an anti-viraland anti-cancer agent. As it turned out, the actual news concernedthe fact that Schering AG is working with a private German firm,Dr. Rentschler Arnzniemittel GmbH to develop, produce andmarket beta-interferon initially for treating hepatitis.This complicates the picture even further, because Schering AG'sU.S.-based marketing arm, Berlex Laboratories, already has rightsto a competing product for treating multiple sclerosis: ChironCorp.'s (NASDAQ:CHIR) FDA-approved Betaseron which is alsoa beta-interferon, though with a slightly different structure. Thatnews sent Chiron's stock spinning: it lost $1.38 on heavy volume of3.8 million shares. The message, according to Bear Stearns analystDavid Molowa, was that Schering AG had decided that its beta-interferon, like Biogen's drug, was more promising than Chiron'sproduct.Biogen's Trial Endpoints Differ From Chiron'sBiogen's Phase III trial differs from Chiron's trials on its Betaseronproduct in several regards, but primarily the endpoints chosen in thestudies. While Chiron measured the annual exacerbation rate andthe proportion of patients who had no exacerbations (and thoseendpoints turned out to be statistically significant), Biogen hasconcentrated on measuring time to disability and secondarily,reduction in exacerbation rate.The two products differ in several ways: Chiron's Betaseron is arecombinant beta-interferon (with a change in one of the aminoacids) produced by Escherichia coli and thus non-glycosylated;Biogen's recombinant interferon beta is a glycoprotein produced inmammalian cells. Chiron's product is administered every other dayand has been reported to elicit neutralizing antibodies in patients,part of the side effect profile, along with what can be described asflu-like symptoms and injection site reactions. Biogen's product isadministered via intramuscular injection once a week. Chiron'sclinical trial data demonstrated that Betaseron reduces relapses, butdid not prove that it significantly affects disease progression.Now that Biogen's Phase III trial results have been released,analysts will be poring over the data to determine for themselveswhich drug has the greater chances for success in treating multiplesclerosis. And that doesn't take into account Teva PharmaceuticalIndustries Ltd.'s (NASDAQ: TEVIY) Copaxone (Co-Polymer 1, orCOP-1), a four-amino acid peptide fragment derived from myelinbasic protein, the antigen that is thought to trigger the autoimmuneresponse in multiple sclerosis. Teva presented its Phase III data onMonday as well. The company had already reported that the resultswere statistically significant in reducing the rate of exacerbations inpatients with relapsing remitting multiple sclerosis. n
-- Jennifer Van Brunt Business Editor
(c) 1997 American Health Consultants. All rights reserved.