MDA LAYS GROUNDWORK FOR COMBINATION DRUG TRIALS
On Jan. 18, MDA Senior Vice President and Executive Director Robert Ross, MDA Director of Research and Patient Services Administration Ron Schenkenberger and other key members of MDA staff met with researcher and clinician Dr. Lawrence Z. Stern of the University of Arizona on the subject of combination drug trials for ALS.
The concept of using controlled human trials to test a combination of ALS drugs becomes increasingly important now that Rilutek has completed the Food and Drug Administration approval process and MDA-funded research in other substances — including several neurotrophic factors — continues to press forward. As with Rilutek, it may turn out that any single drug used alone will provide only a limited effect on the course of the disease. Many researchers feel that formulating an effective therapeutic response will require the combination of a number of ALS drugs.
With the Jan. 18 meeting, MDA resolved to intensify its efforts to establish methodology and funding for drug trials that will allow clinicians to study ALS drugs in combination. MDA staff and Stern consulted with Dr. Leon I. Charash, chairman of MDA's Medical Advisory Committee; Dr. Stanley Appel of Baylor College in Houston; Dr. Michael Brooke of the University of Alberta in Canada; Dr. Benjamin Brooks of the University of Wisconsin; Dr. Rodney Howell, chairman of MDA's Scientific Advisory Committee; Dr. Robert Miller of the Forbes Norris MDA/ALS Research Center in San Francisco; Dr. Lewis Rowland of Columbia University; and Dr. S. Mouchly Small, chairman of MDA's Executive Committee.
It was agreed that MDA's nonprofit status and long history as the leader in ALS research gives the Association an unbiased vantage point when it comes to developing and evaluating combination trials. While pharmaceutical companies have played and will continue to play a huge role in drug development, when it comes to combination trials the companies would naturally tend to favor their own product and stockholder interests. MDA has the advantage of being guided solely by the interests of science and patient well-being.
Pharmaceutical companies will be asked to provide supplies of the drugs to be tested. The Muscular Dystrophy Association of Canada has expressed a preliminary interest in working with MDA in this important initiative.
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 MDA RESEARCHERS SPEAK AT ALS COLLOQUIUM
Some 150 neurologists and researchers were in attendance Jan. 11- 13 at an ALS colloquium in Orlando, Fla., sponsored by the drug company Rhone-Poulenc Rorer. Researcher and clinician Dr. Lawrence Z. Stern of the University of Arizona and MDA staff writer Philip Ivory were there to represent MDA.
In addition to Stern, many other noted MDA grantees were present. Several spoke about their work in ALS research or about current issues in ALS patient care.
On the research front, Dr. Jeffrey D. Rothstein of Johns Hopkins University in Baltimore spoke about the "excitotoxicity hypothesis," exploring the as-yet-unanswered question of whether the loss of glutamate transporters and the resulting buildup of glutamate causes ALS. Rothstein's MDA-funded research into the glutamate inhibitor riluzole helped make possible the development of the first FDA-approved drug for ALS, Rilutek.
Researchers spoke about other possible causes for ALS, including involvement of the immune system. Also discussed was apoptosis, the process of "programmed cell ceath."
Other speakers gave progress reports on two neurotrophic factors being developed as potential treatments for ALS, IGF-1 (Myotrophin) and BDNF. In both cases, it was too early for researchers to make any conclusive statements about the drugs' therapeutic potential.
"This conference provided a rare opportunity for ALS experts across the country to come together and share insights and information," said MDA Senior Vice President and Executive Director Robert Ross. "MDA recognizes the contribution Rhone-Poulenc Rorer has made to increased understanding of ALS through its sponsorship of this event.
" Representatives of Rhone-Poulenc Rorer said they would consider sponsoring such a colloquium again, depending on the feedback they received from participants.
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FDA DENIES EARLY ACCESS FOR MYOTROPHIN
Little more than a week after pharmacies began selling Rilutek, the first drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of amyotrophic lateral sclerosis, another potential ALS drug, the neurotrophic factor IGF-1 (Myotrophin), has suffered an apparent setback in its quest for FDA approval.
Myotrophin, under development by the pharmaceutical company Cephalon and its partner Chiron, was denied treatment investigational new drug (treatment IND) status by the FDA. This means that there can be no early access program to provide the drug to patients on an experimental basis before official approval. It isn't known yet how this negative ruling will affect Cephalon's chances of obtaining marketing approval for Myotrophin, but Cephalon is currently talking with the FDA regarding the drug's status.
Cephalon submitted a treatment IND application to the FDA last October, and announced that if it were approved, a limited supply of the drug would be made available to ALS patients through a computerized random selection process.
That same month, Cephalon announced that findings from the second Phase III trials conducted in Europe and North America indicated that ALS patients taking Myotrophin experienced less disease severity and slower disease progression than those taking a placebo, and that some of the data achieved statistical significance. The FDA now seems to have concerns about the as- yet-unpublished scientific data.
As with Rilutek, MDA-funded basic research contributed to the development of the drug, and a number of MDA clinics have participated in Myotrophin trials. No matter what the final outcome with Myotrophin, MDA will remain steadfast in its all-out commitment to ALS research and will continue to play a crucial role in the development of any substances shown to have potential as treatments for ALS.
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THE ALS NEWSLETTER
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