Boot Camp Emphasizes Industry-Style Approach to HIV Vaccine Development
Industry typically leads the development of new products, conducting the translational and clinical research that is required to turn an innovative scientific discovery or early-stage product that is initially hatched in an academic or government laboratory into an actual drug or vaccine. But this process isn’t as straightforward for HIV vaccine development. HIV vaccine research is led by multitudes of researchers in academic and government laboratories, product-development partnerships, and within the pharmaceutical industry.
Part of the reason is that there are substantial, even unprecedented challenges to developing an HIV vaccine. Several candidates in development, including some developed in partnership with industry, have failed to provide any protection in efficacy studies. Only one vaccine candidate tested to date—a modified vaccinia Ankara (MVA) vector-based candidate in combination with a recombinant protein boost—showed any protection against HIV. These candidates, tested in the RV144 trial in Thailand, provided a marginal 31% efficacy. And while follow-up studies to both understand the mechanisms of this protection and to augment it by modifying the vaccine candidates are either underway or in the works, most other vaccine concepts are in the early stages of research or clinical development. There is also no reliable animal model of HIV infection or definitive understanding of what a protective immune response against the virus even entails. This suggests development of an HIV vaccine is a high-risk endeavor and therefore the traditional model of industry-led product development may not be feasible. To address this, the Global HIV Vaccine Enterprise and Shift Health, a healthcare strategy consultancy, convened a two-day product development Boot Camp on November 15-16 in New York City, bringing together 50 leading vaccine research and product development experts to discuss how industry’s expertise in product development could be integrated in the HIV vaccine field at large.
“The Enterprise had a meeting about a year ago to talk about the interaction between the public and the private sector. One of the important things that came out of that meeting is that you have to think from the beginning to the end all at the same time. So that was the impetus for this project,” said William Snow, director of the Enterprise Secretariat. “We are trying to educate people about how people who know how to make vaccines, make vaccines.” The idea is that incorporating a more industrial-like approach into the HIV vaccine discovery process now may expedite the testing and development of an eventual HIV vaccine. “It will make us more efficient. It will make us smarter,” adds Snow.
The workshop focused on several key components of product development, including strategies for managing pipelines and portfolios, creating target product profiles, translational research, preparing for the risks and potential outcomes of clinical trials, and the best practices for product-development partnerships (PDPs) that are a mainstay of the HIV vaccine field today.
In a session on product and portfolio strategy, speakers from the US National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH; the largest funder of HIV vaccine research in the world), the pharmaceutical industry, and the Bill & Melinda Gates Foundation (BMGF), compared and contrasted how their organizations makes decisions about what ideas to support and prioritize. While industry’s portfolio management is guided by medical need, companies are also driven by the expected net present value of a product, which relies on the commercial market potential for a given drug or vaccine. This makes investment in HIV vaccine research and development a hard sell for many companies and is why foundation and government support is so critical to advancing the field.
“I get the question a lot about how we decide what diseases we work on. It’s not rocket science. It’s quite simple: you just look at the top 10 causes of death in low-income countries,” said Penny Heaton, director of vaccine development at BMGF. “The other thing that may not be that apparent to all, is that we want to fund things that are orthogonal to what others are funding. We don’t want just to duplicate what others are doing,” she elaborated. This means taking on ideas or approaches that would be much too early stage or risky for industry to consider. “We also want to make sure that we’re investing in those things that have the potential of being transformational,” Heaton said.
The differences in how foundations, government research agencies, and industry all manage their portfolios made it clear why PDPs are a necessary part of HIV vaccine development. “Partnerships are really the name of the game here,” said Snow, the first to mention a recurring theme of the two-day workshop.
Part of what drives the growing number and broadening landscape of PDPs in the HIV vaccine field is the steep financial investment required to bring an eventual HIV vaccine to those most in need. “No single entity or sector has individually the resources that are needed to move an HIV vaccine forward in different populations worldwide,” says Ryan Wiley, president of Shift Health. There is also different expertise in each of the sectors involved in research and development for HIV vaccines. “I think we all understand the value that different sectors bring: in terms of innovation and science from academia, resources to mitigate risk and spread risk through foundations and government, and the industrial manufacturing and ultimately marketing and distribution expertise of industry.”
Jerry Sadoff, senior advisor on viral vaccines at Janssen Infectious Diseases and Vaccines, which is now part of Johnson & Johnson, suggested that without these partnerships industry would be unlikely to work in HIV vaccine development at all. “There’s a real need in HIV, in my view, to have these partnerships,” he said. Without these partnerships, “I just don’t think industry would be interested.”
Other industry representatives at the Boot Camp echoed the financial benefits of partnering with government and non-profit institutions, but also recognized that these groups bring more to the partnership than just funding. “Within partnerships you get added values and skills,” said Carols DiazGranados, director of clinical sciences vaccine development at Sanofi Pasteur.
Two of the most prominent partnerships in the HIV vaccine field today involve a variety of funders and academic/industrial partners working to advance candidates into clinical testing. How these partnerships were formed, what their aims are, and how they can provide a model for other partnerships was a major focus at the Boot Camp.
The Pox-Protein Public-Private Partnership or P5 is a large consortium charged with leading the follow-up of the RV144 trial. “The goal of the P5 partnership has been to translate the RV144 learning to South Africa and test modified vaccine components from RV144 that are based on clade C inserts with the goal of both improving the efficacy that was observed in RV144, and ideally prolonging that protection,” said Nina Russell, deputy director of HIV at BMGF.
The P5 involves two major funders: BMGF and the NIH. The clinical expertise is provided by the HIV Vaccine Trials Network (HVTN) and the US Military HIV Research Program (MHRP), which are involved in planning and implementing the RV144 follow-up studies. The P5 also involves two industrial partners: Sanofi Pasteur, which is manufacturing the modified vaccinia Ankara prime, and GlaxoSmithKline, which recently acquired Novartis Vaccines and will provide the p120 protein boost.
As the P5 prepares for eventual efficacy studies in South Africa, its members are actively engaging with regulators, communities, and government health agencies to prepare for multiple possible outcomes. “The path from establishing vaccine efficacy to licensure and rollout will ultimately be a multi-year and complex process,” said Russell. “So that’s what we are thinking about very intensively.”
The other major consortium includes Janssen, Beth Israel Deaconess Medical Center (BIDMC), Harvard, the HVTN, NIAID, MHRP, the Ragon Institute, and the International AIDS Vaccine Initiative (IAVI). This partnership aims to advance an adenovirus serotype 26 (Ad26) vector-based candidate expressing mosaic antigens designed to tackle the diversity of HIV in combination with either an Ad26, an MVA vector, or a purified gp140 protein boost. These candidates are currently in Phase I/IIa clinical trials, spurred by encouraging protection data in preclinical animal studies, with a development plan that aims to test the most promising combination of these vaccine candidates in eventual efficacy trials. The preclinical protection data was what convinced Janssen to get involved. “A bit of exciting preclinical data, even though it’s not proof, is enough,” said Sadoff. “Of course we did get some correlates out of these that looked promising, and having correlates makes things even easier to develop. So that was a second reason why we thought we might be able to develop a vaccine using these constructs.”
Getting Janssen involved was what really propelled these candidates toward a product development pathway. “One of many critical features that allowed a transition from research-oriented to product-oriented development was the committed industry partner,” said Dan Barouch, director of the Center for Virology and Vaccine Research at BIDMC, referring to his partnership with Janssen. “I think that can’t be overstated in terms of the importance of that.”
Other factors that were cited as essential to the success of both of these partnerships was having robust project management, including multiple full-time dedicated staff members committed to advancing the program; close personal relationships between the partners; solvable legal issues; a feasible and scalable manufacturing process; and a clear path to a licensable product. Many times, finding consensus between numerous partners and funders isn’t easy and several speakers addressed some of the issues they’ve faced in making these partnerships work. “It has to be something that not only is a compromise between everybody but also makes sense. I think it’s challenging, but I think it can be done,” said Sadoff.
Although industry partnerships in the HIV vaccine field are few today, Barouch hopes more may be on the horizon. “I think the science has advanced to the point where the HIV vaccine field is worthy of true pharmaceutical investment,” said Barouch. “We’ve seen that with one company and hopefully we’ll see that with others in the next few years. Time will tell.” In the meantime, the Boot Camp provided a diverse group of HIV vaccine researchers from academia, government, and non-profit organizations with a crash course in the types of product development skills that can advance HIV vaccine research, even without an industrial partner.
More information about the Product Development Boot Camp, including a webcast, is available at this link. –Kristen Jill Kresge