BETHESDA, Md. _ An FDA advisory panelvoted unanimously Thursday torecommend Genetic Institute's BeneFixrecombinant Factor IX product forapproval. BeneFix is the firstrecombinant coagulation product forhemophilia B.

"We are really excited by thisrecommendation," said Patrick Gage,chief operating officer for theCambridge, Mass. company. "This is areal medical breakthrough for peoplesuffering from hemophilia B."

While hemophilia B is considered anorphan disease, Gage estimated thatthe worldwide market for Factor IX isabout $150 million. He said that he"expects that BeneFix would be adoptedquickly."

Hemophilia B is an extremely rare X-linked bleeding disorder that affectsapproximately 3,000 people _ mostlymen _ in the U.S. Currently, thepainful and potentially fatal bleedsin joints, muscles and organs can onlybe treated and prevented using FactorIX derived from human plasma leavingpatients at risk for a variety ofblood-borne viruses.

BeneFix is an entirely recombinantform of Factor IX which is produced inculture cells that have been adaptedto grow in media void of human oranimal-derived proteins eliminatingthe possibility for viralcontamination. The product has anidentical amino acid sequence toplasma-derived Factor IX. However, therecombinant form has less post-translational phosphorylation andsulfurization than plasma-derivedFactor IX.

Genetics Institute presented resultsfrom four clinical studies of a totalof 64 patients looking at theirresponses to recombinant Factor IXduring bleeds and surgery. A study ofeleven patients comparing similardoses of recombinant Factor IX withthe plasma-derived product indicatedthat the recombinant product was 28percent less effective than theplasma-derived Factor IX at recoveringpatients' Factor IX levels. Even so,further studies of 44 patients foundthat BeneFix resolved 82 percent ofpotentially fatal bleeds with oneinfusion. And, all bleeding incidentscould be stopped with multipleinfusions of BeneFix.

The committee had major concerns aboutthe limited number of patients thatwere involved in the clinical studiesas well as the possibility that thosenumbers couldn't truly identify likelyadverse events. Panel member CharlesAugust, director of the bone marrowtransplantation program at the MiamiChildren's Hospital, said, "I am veryconcerned by the number of patients inthese studies. Is this regarded asacceptable?"

The company chose to follow standardsdeveloped in Europe for testing drugsin hemophilia B which take intoaccount the relatively small number ofaffected patients. And, SuzanneCourter, director of GeneticsInstitute's clinical program in FactorIX said, "This is an orphan of orphandiseases. We actually had greatenthusiasm from the patients, but itis difficult to have large numbersbecause not all patients are eligiblefor the study."

The only major adverse eventassociated with BeneFix was a bloodclot in the kidney of an otherwisehealthy 31 year-old patient. Thecompany maintained that because it hadbeen 12 days since his last dose ofBeneFix, the drug was not a likelycause. However, Carol Kasper, of theUniversity of Southern CaliforniaOrthopaedic Hospital in Los Angelesnoted, "The time frame does notabsolve the drug."

Kasper, however, said thatpostmarketing studies could adequatelymonitor the likelihood of such eventsand said, "I am satisfied with thenumber of patients in these studiesand would recommend that this drug beapproved."

When first asked to vote on whetherthe company had shown the drug to besafe and efficacious enough to warrantFDA approval, the committee voted 8-to-5 with one abstention becauseseveral members felt that they couldnot agree to recommend the productwithout several conditions. After alengthy discussion, panel member SusanLeitman Chief of the blood servicessection at National Institutes ofHealth proposed that the panelrecommend approval only if the companycontinued to monitor majorthromboembolic events, incidence ofinhibitory antibodies and continue thestudy of newly diagnosed patients whohave never received plasma-derivedFactor IX. The panel unanimouslyagreed.

"We are very pleased that thecommittee was unanimous," said Gage."We came to this hearing fullycommitted to postmarketingsurveillance and completing thesestudies."

Genetics Institute's stock(NASDAQ:GENIZ) gained $1.25 Thursdayto close at $62.25. n

-- Lisa Seachrist Washington Editor

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

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