Biogen Inc. won the first of what could be several rounds in its fightfor Avonex, a beta interferon product that would be the first drug thetop-tier biotechnology company takes to market itself.
A U.S. District Court judge Monday rejected a motion filed byBerlex Laboratories Inc. that sought a temporary restraining order toprevent the FDA from approving the interferon beta-1a product formultiple sclerosis (MS). Berlex has marketed Betaseron, a similarbeta interferon product for MS, since July 1993. Approval forAvonex is expected any time.
The issue, a senior Berlex official told BioWorld Today, is morecomplicated than it may appear, eventually will set a precedent, andcertainly is far from over.
"The decision [Tuesday] was not on the merits of the case but on thespecific point that the FDA hasn't done anything yet" related toapproving Avonex, said Jeffrey Latts, Berlex's vice president forclinical research and development and chief medical officer. "Thecourt is retaining the complaint and is prepared to review it at suchtime as the FDA does something on the Biogen filing."
Assuming the FDA grants approval to Avonex the complaint wouldbe revisited by the judge, Latts said. The next step for Berlex,assuming Avonex approval, would be to request a preliminaryinjunction to block product launch.
Those are only the first two steps in what could become a protractedbattle involving patent issues, cell lines and a small German companythat was in a joint venture with Biogen on interferon beta-1a, but nowis squarely in the corner of Schering AG, the Germany-based parentof Berlex.
`This is the first shot across the bow," said Ed Hurwitz, an analystwith San Francisco-based Robertson Stephens & Co. "Schering andBerlex are going to fight to keep Avonex off the market. The legalcosts are minimal compared to what's at stake."
What's at stake is a market potential of more than $300 million in theU.S. and, for MS patients, access to a drug that slows diseaseprogression and has fewer side effects and a better dosing schedulethan Betaseron.
But is that drug Avonex, or as Berlex claims, one from the privateGerman company, Rentschler Biotechnologie, of Laupheim, whichhad a joint venture with Biogen for Avonex? The joint venture, calledBioferon, was dissolved several years ago. Rentschler purchasedassets from the joint venture from a German bankruptcy court andsold rights to Schering AG.
Material for the clinical trials that showed the efficacy of the originalinterferon beta-1a was produced by the joint venture. Biogen, ofCambridge, Mass., meanwhile, went on to use a different cell line atits own manufacturing facility to produce a product, Avonex, that wasdeemed comparable by the FDA. Rentschler owns product from theoriginal cell line. Biogen owns data from the clinical trials.
"When the facts are fully examined they will show it's the Rentschlerproduct that should be on the market because it's the one tested inclinical trials in MS patients," Latts said. "That's the core argumentbehind this suit."
The lawsuit filed Friday, however, cited the Orphan Drug andAdministrative Procedures acts. The Orphan Drug Act givescompanies with products addressing small markets seven years ofexclusivity from copycat products. The administrative portion of thesuit deals with possible differences in the product the FDA willapprove and the one tested in trials.
C. Anthony Butler, an analyst at Raymond James & Associates Inc.,in St. Petersburg, Fla., said bioequivalency studies such as those forAvonex have been used in the past for approval of manufacturingchanges.
Kathryn Bloom, Biogen's director of corporate communications,cited a recently issued FDA guidance document stating the agencyhas approved manufacturing changes made during or aftercompletion of studies when a comparison of the products assures thenew one will be effective.
Biogen Has The Advantage, Analysts Say
"Biogen will prevail," said Butler, adding that no one can predictwhat if any delay might be ahead because of legal actions. "If youunderstand the biochemistry, the biology and molecule's mode ofaction one might conclude the suit doesn't have merit.
"What Berlex does for Round 2 is an interesting statement, andwhatever else they have up their sleeve is an interesting statement,"Butler said. He said he envisioned three scenarios that Scheringmight use to block Avonex, one of which was implemented Friday.The other two relate to a patent on manufacturing of beta interferonin mammalian cells and the possibility of Rentschler attempting to getapproval of its product in the U.S.
Hurwitz agreed that Berlex will pursue all avenues to keep Avonexoff the market. He, too, sees Biogen as the eventual winner.
Investors felt confident enough about Biogen's position to push thestock up $2.63 Tuesday to close at $65.88. Biogen's stock(NASDAQ:BGEN) lost $1.50 when the suit was filed Friday to closeat $61, but gained back that loss and then some on Monday.
Latts said Berlex already has had discussions with the FDA aboutpossibilities of getting the Rentschler product on the U.S. market. Butit appears new studies would be needed because Biogen owns thetrial data. "Down the road," Latts said, "there are possibilities forcompromise. One is for all three to come to market.
Setting Industry Precedent
"It's a very touchy issue, very complex in a regulatory sense," Lattssaid. "There is no example for this anywhere. Whatever is decidedwill decide the precedent."
He said technology is not advanced enough at this time to show withconfidence that a biological production process can producecomparable material.
Latts said approval of Avonex, which also has orphan drugdesignation, could preclude Rentschler's product from coming tomarket for seven years (Berlex granted a waiver so the Rentschlerproduct could come to market despite Betaseron's orphandesignation). "Does that seem fair? This company invented themolecule; they own the technology." And, he added again, it's theproduct that was proved efficacious.
Bloom said the idea that Rentschler created the drug is"preposterous." She said the German partner's role was as a "contractmanufacturer."
The new Biogen product, while not used in previous trials, currentlyis being tested in extension studies in more than 300 patients, manyof whom were in the Phase III study.
"This is the most complicated, messy thing anyone has seen in termsof development," Latts said. "I suspect this [Tuesday's ruling] is notthe definitive ending act in the play." n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.