The Bay Area Reporter - September 15, 1998
Mike Donnelly, ACT UP/Golden Gate Writers Pool

Some complications of AIDS are going the way of the dinosaur. The incidence of PCP and KS are way down. This can be attributed to triple combination therapy and prophylactic drugs such as Bactrim or Septra. Other complications however, are becoming more prevalent. Peripheral neuropathy is on the upswing either from drug toxicity or from HIV disease itself. People with AIDS want relief from the numbness and pain of neuropathy. There is also a push to solve the ongoing problem of dementia, which affects the quality of life of many people with AIDS. Recently there have been drug continuation problems for two AIDS Clinical Trials Group (ACTG) neurological complication studies.

Nerve Growth Factor trial

ACTG 291, a trial for Nerve Growth Factor for Peripheral Neuropathy, did not have drug continuation included in the original trial design. This is a drug is made by Genentech, a large biotech company in the Bay Area.

The company was conducting trials for peripheral neuropathy caused by diabetes. Matt Chappell, who was a community member of the ACTG, finally persuaded the company to provide drug for the ACTG trial for AIDS-related peripheral neuropathy. The trial was a placebo controlled trial so there was a chance that participants would not get drug. As the participants finished the 18-week placebo trial many felt they were receiving benefit from use of the drug. The drug also appeared to be safe. Eventually Chappell and other community members, as well as the researchers, persuaded the company to add a 48-week open label drug use to the study.

Dr. Justin McArthur at the World AIDS Conference in Geneva presented the positive study results. The company announced a 2,000-person expanded access program, starting with the 200 participants of the clinical trial. Unfortunately, the expanded access program has not opened up to others who suffer from HIV-related peripheral neuropathy. The company has opened a hotline number (1-888-662-6728) for expanded access, but has not heard from the community and the program has stalled. The company must hear the needs of the community.

Small company concerns

Constantin Yiannoutsos, the statistician for ACTG neurology studies from the Harvard School of Public Health, has concerns about small companies involved with the ACTG in clinical trials. "The current model of collaboration between the ACTG and drug companies, which has worked well in the case of antiretroviral drug development may not be applicable here, to the detriment of patients. This is because, especially in neurology, we are dealing with small upstart companies."

Constantin continues, "Where there is a definite incentive for the Glaxos and Bristol-Myers, to provide compassionate use of their drugs and quickly take over drug development from the ACTG, this is much more difficult with most of the agents and companies under the purview of the ACTG neurology group."

He urges the ACTG and the community "to find a vehicle where patients that feel helped by an experimental drug will be guaranteed access to it at least until the final analysis. At that point, a positive result should provide adequate incentive to the company to continue development on its own while a negative result would steer patients to other alternatives."

Case of a small company

ACTG 301 is an ongoing study of Memantine for AIDS dementia. The trial includes blinded drug or placebo for the first 16 weeks and then includes period of 12 weeks on the study drug. Because the trial is accruing participants slowly, some individuals have completed the trial and no longer have access to the drug.

Study coordinators and participants from the University of California, Los Angeles (UCLA) and the University of Kentucky brought this problem to the attention of the ACTG. Many of the participants were feeling better and some were even returning to work. Since there is no other drug for dementia, they expressed a desire to continue to have access to Memantine.

Unfortunately there was no mechanism for these participants to continue to receive Memantine. They had completed the trial and there was only enough of the drug manufactured for the trial. On top of that the company had decided not to continue production of the formulation of the drug used in the trial. They would use the tablet formulation available in Europe for future trials.

The company that makes Memantine in the United States is Neurobiologic Technologies Inc. (NTI), a small biotech company based in Richmond, California. Like many small start-up companies they have 10 employees and do not have the resources to monitor an expanded access program. Lisa Carr, vice president of medical affairs for NTI, said this week that the company would produce enough Memantine "so all patients can continue for one year. Safety monitoring is a major concern." Now that the company has agreed to supply the drug, the clinical trial team needs to amend the clinical trial to include a longer open label use of the drug. This should take a few months for all the regulatory hurdles but this appears to be a story with a happy ending.

How do we overcome future problems of access to these drugs? It is clear the community, clinical trial investigators, the companies and the government must collaborate to find a new mechanism to solve this troubling problem and assure access to all promising therapy.
980915
BR980901

Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .