At the 12th World AIDS Conference in Geneva, Justin McArthur, M.D., of Johns Hopkins in Baltimore, reported on ACTG 291, a phase II study of 271 participants with neuropathy. They were treated with injections of two different doses of NGF or placebo for 18 weeks and with open label NGF for an additional 48 weeks (late breaker 11/abstract 32454). Dr. McArthur presented the results for the first 18 weeks. Outcomes were measured by changes in pain severity using a self-administered rating scale and neurological examinations.
The two treatment groups showed a statistically significant decline in pain intensity, both average daily pain and global pain by week 18. This translated into a reduction in participants' pain, so that it was now judged to be "mild" rather than "moderate." Those with higher baseline pain severity experienced greater benefit from NGF. Participants with mild baseline pain did not experience a treatment effect. There was a slight improvement in neurological function in one category. There was also no indication of regeneration of nerve fibers, but Dr. McArthur stated that 18 weeks of therapy might not be long enough to repair nerves that have potentially been damaged over the course of several years. Finally, no significant adverse events occurred, with the exception of discomfort at the injection site, which was greater in the higher dose group.
Genentech planned to file a new drug application with the FDA this year. But after reviewing the data, the agency decided that the ACTG 291 trial results alone could not demonstrate safety and efficacy to warrant marketing approval. An NGF expanded-access program for HIV-associated neuropathy was in development to tie in with the FDA filing, but with the application suspended, the program will not go forward as planned. Participants from ACTG 291 can continue to get the drug for an additional 48 weeks through another trial extension but there is no access for people suffering from neuropathy who did not participate in the original study.
Genentech is not currently planning any further studies for NGF in the HIV population. The company is instead developing the drug for the treatment of diabetic neuropathy and expects to file for that indication next year. If NGF is not approved specifically for HIV-neuropathy, then it will have to be prescribed "off-label" if used in people with HIV, and this may cause reimbursement problems. The drug is expected to be expensive. Without insurance coverage, it will be out of the reach of all but a privileged few.
Community activists believe that Genentech has not invested enough of its own resources in developing NGF for HIV. It has mainly relied on the government-sponsored AIDS Clinical Trials Group (ACTG) to conduct trials. The company is now encouraging ACTG investigators to propose further studies on changes in nerve fiber function. However, it is Genentech that should take responsibility for designing trials that will lead to drug approval. At this point, it may be that company management believes that there is simply more money in developing NGF for diabetics. For information on the status of NGF or to comment, call Genentech at 888/662-6728.