It was clear drugmaker Genentech had a potential public relations mess on its hands. AIDS patients who had participated in a government-sponsored trial to test Genentech's experimental recombinant human nerve growth factor (rhNGF) were angry that the company had abruptly halted the study in April and cut off their supply of rhNGF. This despite claims by patients that the treatment eased the pain and dysfunction caused by a degenerative nerve disorder, HIV peripheral neuropathy. Prominent neurologists who had administered the trial were outraged as well that the company said it had no interest in pursuing further studies.
AIDS activists demanded Genentech explain itself. Patients and their supporters sent irate letters to the company and the media. Two small California newspapers ran stories on the company's actions, and a Mother Jones reporter was working on another.
Then, suddenly, Genentech invited a handful of key activists and patients to "discuss rhNGF" and "options for next steps."
After the July 2 meeting, Genentech made a surprising announcement: It would dispense its remaining supply of rhNGF to trial patients who wanted the drug, and it would be willing to discuss providing the drug to a third party for a new study (two things the company had previously said it had no interest in doing). The drugmaker's move even earned it some positive coverage from the Associated Press.
How does Genentech explain its change of heart? "This was really the first time it had been clear to us that there was a constituency of patients that ... felt they were benefiting from the drug and really wanted to stay on it," says Dr. Stephen Dilly, vice president of medical affairs at Genentech.
Patients and physicians, however, dispute Genentech's claim. Activist and patient liaison Mike Donnelly says he has benefited from rhNGF since he entered the trial in 1996 -- and Genentech knew it. "NGF made a big difference in my life; I could be mobile again," says Donnelly, who couldn't walk more than a few blocks before the trial. "[Genentech] has known all along that people wanted to stay on this drug."
Tom McElroy, another trial patient, made his feelings known loudly. In April and May he made frantic calls and sent letters to tell the company about how the treatment had helped him. "Before rhNGF I had lost the ability to walk a block or climb a flight of stairs," McElroy wrote in May. "Since rhNGF, I am mobile, independent, and even went camping and did some very light hiking." McElroy asked Genentech to continue supplying rhNGF to trial participants. Genentech replied simply that the drug "will not be available."
AIDS groups and doctors say it was only because of their pressure that the drug was ever available to HIV patients. Genentech had developed rhNGF for a different -- and potentially much more profitable -- market: the more than 4 million Americans who suffer from diabetic neuropathy. Only about 200,000 AIDS patients have peripheral neuropathy, caused by HIV or certain HIV drugs, with some 25,000 new cases a year. But in 1996, while it funded a large-scale Phase III trial on rhNGF for diabetes patients, Genentech did agree to provide the drug for a smaller trial sponsored by the AIDS Clinical Trials Group (ACTG), funded by the National Institutes of Health.
Doctors who conducted the HIV trials saw very positive results: rhNGF didn't make patients sick or interact with other drugs (some AIDS drugs can bring on additional illness by interacting with other medicines), patients got great relief from pain, and there was evidence of modest neurological improvement. Genentech disputes the validity of the results. The neurologists agree the results were not conclusive, but they determined that rhNGF showed enough promise to warrant further testing. "Some patients who responded were people who had responded to nothing else," says Dr. Elyse Singer, who directed the HIV study at the University of California, Los Angeles.
Last April, though, Genentech pulled the plug on further rhNGF studies when the drug proved ineffective in the diabetes trial. With their supply cut off, AIDS patients eventually exhausted their remaining doses and began to regress physically. McElroy says he felt the effects within days. "Just the weight of the comforter bearing down on one foot was unbearable," he says.
Genentech also showed an unwillingness to supply the drug for other studies. In November 1998, Dr. Justin McArthur, the principal investigator for the HIV trial and deputy director of neurology at Johns Hopkins University, sent Genentech a proposal for a follow-up study. He didn't want funds -- there was enough money from a running NIH grant to back another study of several hundred patients; all he needed was for the company to supply the rhNGF. According to McArthur, he was sent a reply saying that Genentech would not provide rhNGF for future studies.
Even now, with the company's apparent reversal, McArthur is cautiously optimistic at best. "No one's breaking open the champagne," he says. Genentech says it will start distributing rhNGF to trial participants who want it. There is enough of the drug, company officials say, to last one to two years, though no one can say precisely how much or when patients will actually receive it -- a critical point since some supplies will reach their expiration dates by year's end.
Beyond the issues of dispensing the drug, there are questions surrounding Genentech's support of future testing. The company says it is willing to provide rhNGF for future study but that it would do so only for a yearlong, pivotal Phase III study with at least 1,000 patients. And, according to Genentech spokesman Geoff Teeter, the company -- which had revenues of $1.2 billion in 1998 -- will not fund such a study. But without corporate backing, doctors say, a large-scale trial is unlikely to happen. "The ACTG has taken the position that pivotal studies should be sponsored by pharmaceutical companies, not tax dollars," says McArthur.
Doctors hope that trial patients will resume getting the drug, but they remain skeptical of Genentech's sudden compassion. "It doesn't explain the capricious and cynical nature that's been displayed here -- that you can turn off a study and turn it back on months later," says McArthur. "It's not the proper way to treat patients, particularly those who are suffering."