By Karen Pihl-Carey

A study conducted at Wayne State University¿s Multiple Sclerosis Center in Detroit indicated that only two of the three approved MS drugs ¿ Copaxone and Betaseron ¿ significantly reduced relapses in patients. The market-leading Avonex did not show such results, researchers said.

Biogen Inc., which markets Avonex, criticized the study, saying it was poorly constructed.

Results of the prospective, controlled, open-label study, which compared the effects of the three FDA-approved drugs for relapsing-remitting multiple sclerosis (RRMS), the least severe form of the disease, were presented at the American Neurological Association conference in Seattle. Omar Khan, director of experimental therapeutics and research at Wayne State¿s MS Center, said patients on Avonex failed to show a significant reduction in relapses or in scores on the expanded disability status scale (EDSS), used for judging the clinical status of people with MS.

¿If you¿re going to make a direct, head-to-head comparison of these therapies, you have to perform the proper experiment. This trial was not the proper experiment,¿ Biogen spokeswoman Kathryn Bloom told BioWorld Today. ¿What you have to do is a prospective, randomized, double-blind study.¿

Timothy Vartanian, an academic neurologist who is director of the multiple sclerosis center at Beth Israel Deaconess Medical Center in Boston, also criticized the study. ¿It is an excellent example of a poorly designed study, and it would really be a shame if patients used this misguided information at the expense of information gained at painstakingly designed, well-controlled studies,¿ he said.

Although the study was non-blinded and non-randomized, results are similar to those previously reported in randomized, placebo-controlled Phase III studies, Wayne State¿s Multiple Sclerosis Center said in a statement. The study supports the early initiation of treatment and showed that Copaxone had a highly significant effect during the second half of the 12-month treatment period.

¿No, it was not double-blind and it wasn¿t randomized. That¿s true. It wasn¿t intended to be,¿ Khan told BioWorld Today. ¿We wanted to do an open-label treatment study and we wanted to see, when patients were given the information of treatment options and given the choice, does that make any difference on treatment outcome? That was what this was about, because it is almost impossible to imagine that any pharmaceutical company is going to fund this study, spend millions of dollars to do a double-blind, placebo-controlled study. That would be the most accurate way to answer the question, but we all know it¿s not going to happen.¿

A total of 156 patients were invited to participate in the study, beginning in August 1996. They were given the choice of the three therapies or no therapy, with 40 choosing Avonex, 41 choosing Betaseron, 42 choosing Copaxone and 33 choosing no treatment. Each group had similar age and disability ratings.

Wayne State¿s MS Center said researchers conducted a disability assessment at the beginning of the study to determine each patient¿s score on the EDSS, which measures a patient¿s ability to function through a series of strength, coordination, manual dexterity and other neurological tests. The study found a statistically significant improvement in disability scores in patients who received treatment with Betaseron and Copaxone, but not Avonex, compared to patients on no treatment.

Bloom said the Wayne State study was not in line with what Biogen found in clinical studies of Avonex. ¿In MS, all the thought leaders have increasingly agreed over the years the endpoint of the drugs is the long-term effects on disability,¿ she said. ¿This study was not randomized. It was not blinded. It was observational of what happened to certain self-selecting patients over a limited period of time. The results do not support the scientific rigorous studies that we did on Avonex. These do not even support the trials of the other two.¿

Avonex (interferon beta-1a) has been on the market since May 1996 and is the leading multiple sclerosis drug. Produced in mammalian cells, it is taken once a week by intramuscular injection. It brought in $304 million in U.S. sales in 1998. Most recently, sales were boosted to $163.4 million in the third quarter. Avonex holds 60 percent of the U.S. market and 40 percent of the European market.

In clinical studies, Avonex helped decrease the rate of brain tissue loss in the second year of treatment.

Copaxone, which is manufactured by Jerusalem-based Teva Pharmaceuticals Industries Ltd., showed a 35 percent reduction in new lesions and a 33 percent reduction in relapse rates. It was cleared for U.S. marketing in December 1996.

Betaseron (interferon beta-1b), manufactured by Chiron Corp., of Emeryville, Calif., showed a reduction in frequency and severity of acute attacks in patients with RRMS. It received U.S. marketing approval in 1993.

¿The completion of the Betaseron, Avonex and Copaxone Phase III clinical trials were the first clinical trials that gave us solid evidence of the efficacy of certain agents in the treatment of MS,¿ Vartanian told BioWorld Today. ¿They were, for the most part, well-designed, well-executed studies, with some minor exceptions.

¿This Wayne State University study by Dr. Kahn is really the antithesis of what one would want in an MS clinical trial ¿ or any clinical trial, for that matter,¿ he said. ¿It was an open-label study, which lends itself to inherent biases. It was not randomized. It was not placebo-controlled. And it involved a small number of patients in each arm of the study. And it was executed over a short period of time. So it is, again, everything we don¿t want in an MS clinical trial. There is absolutely no useful information to be gained from that study.¿

But Jeffrey Latts, chief medical officer for Montvale, N.J.-based Berlex Laboratories Inc., which markets Betaseron, said the study is a ¿real-world clinical study where practicing neurologists are using therapies in the way they are normally used,¿ and that the information does have some value.

¿Sure, that¿s not a big, double-blind study, but at the same time, it¿s a fair number of patients, and I think clinicians will look at the results in that context, along with all the other results out there,¿ Latts told BioWorld Today.

¿The study is not designed to make superiority claims and it is not designed to bash Avonex,¿ Khan said. ¿We are simply reporting what we saw.¿

Chiron¿s stock (NASDAQ:CHIR) closed Thursday at $29.312, up 75 cents. Teva¿s stock (NASDAQ:TEVA) closed at $49.562, down $1. Biogen¿s stock (NASDAQ:BGEN) closed at $78.625, down $2.312.