Every once in a while a headline recalls a vivid incident from the past. Reading about a promising HIV vaccine that showed a near 100% immune response rate in early tests from Inovio Pharmaceuticals backed by National Institutes of Health (NIH) funding, triggered a memory from years ago. We were working with the top researchers at the Dept. of Veterans Affairs hospital in San Francisco assessing their research capabilities for possible industry partnerships. One doctor sadly recalled the days in the 1980’s when patients started showing up with a new disease that quickly led to an agonizing death as they wasted away before his eyes. There was little understanding of what was happening so the best that could be done was making their final days as painless as possible. Nearly 36 million people around the world perished.
Twenty years later HIV had gone from a death warrant to something patients can manage because of a remarkable partnership between advocacy groups, NIH, Congress and the life science industry. NIH took the lead in spurring the development of early HIV drugs, helping companies gain a better understanding of the disease and ways to alleviate it. After that, companies took over. Now they fiercely compete to develop more effective approaches (see GSK investors cheer as Gilead’s HIV candidate bictegravir fails to beat their own Tivicay).
Today NIH finds itself whipsawed despite its record of success. The pending budget request from the Administration would reduce its funding while critics question why industry partners require exclusive rights to intellectual property to develop needed treatments. Last week a story on National Public Radio implied that companies would line up for non-exclusive licenses to develop a Zika vaccine because of government support of the R&D. That only one company (Sanofi) was even willing to apply for an exclusive license was brushed aside. Clearly, there’s a misunderstanding of why partnerships with industry are necessary and the risks involved in developing treatments for little-understood diseases.
Here’s how Dr. Anthony S. Fauci, the Director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) explains it:
NIAID enters into public-private partnerships to stimulate investment in innovative ideas, preclinical and clinical trials, and products that might otherwise be too speculative to be considered by private companies. Government funding encourages companies to devote resources to public health needs by helping to underwrite work that might not otherwise be a high priority in the absence of immediate profit potential. These collaborations have benefited the public good, yielding many vaccines and other biomedical interventions in use today.
Developing an effective HIV vaccine remains a formidable challenge because there’s only a narrow window in which to counter the virus. For the millions living with HIV– and millions more at risk of contracting it– this is much more than an academic exercise. Few companies can fund the fundamental science needed to find the path forward so once again NIH is stepping in. NIAID is supporting critical research and early stage development through proof of concept for potential HIV vaccines like Inovio’s.
I asked Dr. Carl Dieffenbach, who directs NIAID’s Division on AIDS, about his goals and why industry partnerships are necessary. He began by explaining that the origins of the program trace back to the early days of HIV/AIDs epidemic when patient advocacy groups and Congress urged NIH to take the lead in gaining a greater understanding of the disease. “We do what industry can’t or won’t do. We support innovative approaches until a proof of concept has been established. After that, we get out of the way as the private sector can take it from there.” That’s what happened with HIV drugs.
Now the focus is on developing an effective HIV vaccine which has proven exceptionally difficult as this is more expensive and riskier than developing a new drug. NIAID is supporting approaches like that of Inovio whose vaccine shows potential promise in early tests. The question is whether the vaccine can maintain its efficacy over time, so additional NIAID support is necessary. The next step is to go from trials on 75 patients to studies on 2,600 to 4,000. If everything goes according to plan (which is highly unusual), the vaccine will proceed to Phase II testing for two years or more, then move onto clinical trials, which could take another six to seven years. Even in the best case, there’s still a long, perilous path ahead. However, if the vaccine can show a 65-75% efficacy rate in patients it would be a significant breakthrough in preventing HIV infection.
Dr. Dieffenbach added that how far along the pipeline his program will support any particular project depends on how it’s proving out and what other discoveries warrant support. The later stages of development where the risks and expenses accumulate are assumed by the industry partner, which often needs to raise venture funding while developing a manufacturing and sales capability. There’s no free lunch in the NIAID program.
One of the questions frequently raised about NIH/industry partnerships is why the government doesn’t mandate the price of resulting products. Dr. Dieffenbach says that experience has shown that market competition is the best regulator. “In the early days, HIV drugs cost $12,000. Today patients around the world are paying about $200 annually for their treatments. This decline didn’t happen overnight but as more treatments become available prices fall. We’re seeing the same thing happen now with the Hepatitis C medications.”
Dr. Dieffenbach’s passion for his work is immediately apparent. He clearly loves what he’s doing and is driven by the realization that millions of lives will be impacted by what his program achieves.
With all the formidable scientific barriers confronting development of an effective HIV vaccine, Inovio lays out in a press release other equally challenging hurdles the company faces in bringing the vaccine to the marketplace. Among these uncertainties are:
…issues involving patents and whether they or licenses to them will provide the company with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether the company can finance or devote other significant resources that may be necessary to prosecute, protect or defend them…”
Those who believe that patents aren’t important or that companies would undertake the rigors of commercial development with only non-exclusive licenses don’t understand the realities facing innovators like Inovio.
Of all the things Inovio has to worry about, it’s sad that one is a legitimate concern whether they can trust the U.S. patent system to protect the inventions the company is built around. Unfortunately, there’s good reason for anxiety. If they are successful their patents could be subjected to years of post-grant reviews by competitors and those who believe life science patents harm the public interest. Even if their IP holds up, they may face howls from critics and politicians demanding that the government step in to issue compulsory licenses so others here and abroad can copy the vaccine. For the 35 million living with HIV, the scientific barriers aren’t the only ones standing in the way of effective treatments.
Still, HIV patients and their supporters should be encouraged that they have champions like Dr. Dieffenbach. They should also be thankful that companies like Inovio are willing to work with NIH/NIAID to meet daunting public health needs. Like true partners, they are fighting side by side to make life better for all of us. You’d think that’s something everyone would support.
Bayh-Dole and the Renaissance of American Innovation
Called by the Economist Technology Quarterly “Possibly the most inspired piece of legislation to be enacted in America in the past half century” by allowing universities to partner with industry the Bayh-Dole Act helped pull the US out of the doldrums, restoring American competitiveness. Here’s a podcast on how the law came to be, what it’s done and how it can unravel if it’s taken for granted: humanPoC.com/joe-allen