Five years ago Merck ($MRK) investigators stunned everyone working in the AIDS research field with the news that they were abruptly halting a study of a prospective HIV vaccine after the data began to make clear that it wasn't only failing to guard against the virus, but appeared to increase the risk of becoming infected. Now researchers have followed up to confirm that the worst case scenario was true.
The sudden about-face on the vaccine forced investigators as well as the NIH to do some serious rethinking about the R&D work being done on HIV vaccines. Not knowing exactly what went wrong, another big trial was scrapped on a similar vaccine. And as The New York Times reports today, further work has been carried out in slow motion, delivering at best mixed results.
The new study tracked the health of 1,836 men enrolled in the Merck trial for a further two years. Almost 10% later became infected, with uncircumcised men and men with high levels of antibodies for the Type 5 adenovirus most at risk. As the vaccine was constructed using a weakened adenovirus 5, scientists speculate that may have boosted the presence of CD4 cells in the blood, creating the kind of "target-rich" environment that HIV thrives on.
But that's conjecture. Investigators still aren't certain what went wrong, only concluding that the result had to be biologic. As a cautionary tale, the Merck trial will continue to serve as a reality check for everyone in the field.
With an FDA panel looming, agency staff raised concerns about the risk of kidney damage seen in studies of Gilead Sciences' ($GILD) HIV treatment Quad. The staff review comes days ahead of a panel of non-agency experts who will decide whether to back approval of the new four-drug pill, which could sure up Gilead's position as the leading maker of AIDS drugs for years to come if approved later this year.
The kidney damage could warrant monitoring of patients taking the drug, the FDA staff briefing said, according to Bloomberg. Studies showed that more kidney problems were seen among patients on Quad than other HIV meds, including four patients who suffered kidney failure and one who developed a rare condition that caused renal problems. However, fewer patients quit taking Quad in studies because of side effects than existing meds, a plus for Gilead's case for the combo pill to provide a safer option for treating patients.
Gilead has captured headlines this year for its nearly $11 billion buyout of Pharmasset to gain a footing in the hot field of oral hepatitis C treatments, yet the California biotech company's bread and butter has long been drugs for HIV. Quad offers Gilead a chance to keep the company's reign in the HIV market alive after its patents for top-seller Atripla end, Reuters reported. Also, Quad consists of four Gilead drugs and is taken once a day, while Atripla combines Gilead's two-drug treatment Truvada with Bristol-Myers Squibb's ($BMY) Sustiva.
The advisory panel meets on Friday to discuss Quad, and the FDA will factor in the panel's votes in the agency's decision on approval expected by Aug. 27, Bloomberg reported. Gilead's experimental drug is expected to become a blockbuster product if approved.
Shares of NeurogesX, already badly beaten up over the past year, tanked after regulators raised questions about the efficacy of its pain patch for HIV-related pain. Its stock ($NGSX) dropped to as low as 75 cents a share and then recovered somewhat by midmorning as analysts sifted through the agency's remarks, which are intended to help shape an expert panel review coming up Thursday.
Wedbush analyst Gregory Wade tells Bloomberg that he was none too surprised to see the critical remarks. And even though he doesn't believe that the in-house regulatory review of the application will prevent a vote in its favor, any approval still wouldn't do much to improve the company's prospects.
About 1 in 3 HIV patients suffers from HIV-related neuropathy, notes NeurogesX. But one of the regulators doesn't believe that they'd be well served by Qutenza.
"It would not be in the best interest of these patients for us to approve a product for which substantial evidence of efficacy has not been demonstrated, or one for which the benefits do not clearly outweigh the risks," said Bob Rappaport, director of the agency's division of anesthesia, analgesia and addiction products, according to the Bloomberg report.
By David Welch, President/Senior Producer at M2 MultiMedia
When the HIV/AIDS epidemic became widely known in the early 1980s I lived in San Francisco. I lost many dear friends during those years. That made working on “HIV/AIDS and Biotechnology” very personal to me.
Thirty years later and despite an all-too-common public perception that this terrible disease has been solved, the research to find a vaccine is actually more important than ever. The sad truth is that the cost in both human lives and economic treasure remains astronomical.
Producing this short film for BIO about the role of biotechnology in the on-going fight to save lives and dollars brought me face-to-face with three awesome individuals: a researcher, a patient, and an advocate. The researcher is Dr. David Asmuth, one of the world’s leading HIV experts. The patient, Brian Brown, received VACC-4X, a biotech vaccine produced by Bionor Pharma, in a clinical trial and went a full 18 months without anti-retroviral treatments. The advocate is Stephen Bailous, executive vice president of the National Association of People with AIDS (NAPWA) — he’s also an HIV survivor.
Together, these three men send a compelling message to all of us: If we are to conquer HIV/AIDS the necessity to fund sustained biotechnology research has never been more vital and more hopeful.
I wish to thank our entire team, especially our director Emily Deckelman, for their commitment to producing this important video.
David Welch is President/Senior Producer at M2 MultiMedia, a science oriented video production company in Rockville, MD. His email is dwelch@m2inspired.com