Insights From Industry Experts: Developing Vaccines for Rare Diseases

Rare Diseases and Vaccines

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Vaccine development for rare diseases presents unique challenges that require innovative solutions and collaborative efforts. In a Q&A session with Phyllis Arthur, MBA, senior vice president of infectious diseases and diagnostics policy, and David Thomas, vice president of industry research, both from BIO, Infection Control Today^® ICT^® examines the complexities of vaccine development for rare diseases. Their insights shed light on the multifaceted landscape of rare disease vaccine development, from scientific challenges to investment trends and policy recommendations.

ICT: Can you share insights into the challenges of developing vaccines for rare diseases compared to more common diseases?

Phyllis Arthur: Because these diseases affect a small population or occur rarely as outbreaks in countries or specific populations, vaccine development in this space is unique. It can be very difficult to figure out the exact population that would benefit most from routine immunization. The selected population has to be disproportionately susceptible to a rare disease, but it must be a large enough population for statistical purposes in clinical trials to clearly demonstrate efficacy and safety. Getting enough of those patients to participate in clinical trials takes a very long time or an unexpected outbreak. And the clinical trial process for any drug or vaccine is already extremely complicated, expensive, and time-consuming.

David Thomas: BIO released a report earlier this year on the scientific and investment trends in global vaccine development. In the report, we found that only 3.4% of the total venture capital raised in the past decade went to companies with infectious disease vaccine programs. What that tells us is that vaccine development overall is seeing significant underinvestment. As rare infectious disease vaccines are a subgroup of that investment, it could be considered a neglected area of interest.

ICT: What role does the rarity of a disease play in the decision-making process for pharmaceutical companies when considering vaccine development?

DT: For many vaccine programs, the business and investment case is very challenging for several reasons. Risk is compounded for vaccines versus other areas because the active ingredient can only be used for one pathogen. In contrast, other areas of development, such as oncology, neurology, or inflammation, often have multiple indications that can be explored should one indication fail.

The research and development (R&D) cost can also be substantially more than in other areas due to the large size of enrolling healthy people into trials versus patients with disease. For example, Phase III clinical trials can enroll tens of thousands of patients for a vaccine but often only 500 for a cancer treatment. When it comes to rare infections, the issue is making the trial large enough to find the rare infections in the untreated arm of the trial. Additionally, the company will need to have other programs to fall back on if the new vaccine is successful at eradicating the rare infectious disease. This diversified project portfolio approach requires additional funding at the beginning of the company's R&D work.

The above risks make public-private partnerships a smart choice between industry and non-profits or governments, as they can add financial and scientific support to bioscience companies.

PA: For even rarer diseases that are still worth immunizing people against because they carry mass outbreak potential, public-private partnerships are an absolute necessity. Thankfully, we do have public-private organizations, like the Coalition for Epidemic Preparedness Innovations (CEPI), that work with industry to develop vaccines against pathogens that have outbreak potential but are not so endemic that shots are commercially viable on their own. Some companies are working with CEPI to finalize clinical trials on rare diseases like Lassa fever, Nipah virus, and Rift Valley fever.

DT: Vaccines are especially reliant on these types of partnerships because their revenue models are fundamentally different from therapeutics. Sometimes, you won't even know you'll need to deploy a vaccine until you do. It's possible for a shot or the underlying technology behind it to be unused for years until an outbreak appears. That underscores the importance of public funding, whether from governments or non-government organizations.

ICT: Are there unique scientific challenges associated with developing vaccines for diseases with low prevalence?

PA: One challenge is surges in cases followed by a decline that inhibits clinical trials. Take the Zika virus, for example. We got so far along in developing a vaccine during the outbreaks in 2015-2016, then got stuck because we didn't have many traceable cases anymore—which, of course, is a good thing for public health but difficult for companies in the middle of vaccine development.

The question becomes: how do you finish the clinical trials when the epidemiology changes and you can't finish the work that you're doing? That's the hard part about rare infectious diseases—many don't have the endemicity to have a full clinical trial process. They go through some of the phases, where there are smaller trials, and then they are poised for a larger trial in a population when, unfortunately, an outbreak occurs in a geography. The Ebola response was like that, and companies working on vaccines for diseases such as Lassa fever, Nipah virus, and Rift Valley fever that is, in essence, how they will finish the clinical trial process. There is, therefore, this waiting game that vaccines for rare diseases have to go through as a vaccine candidate waits for the unpredictable to occur.

ICT: Can you discuss the importance of patient advocacy and involvement in driving research and development for vaccines targeting rare diseases?

PA: Patients play a meaningful role in advocacy and medicine development, but it can be especially challenging in this context. Because these diseases are rare, there are fewer patients to begin with. Some advocacy may also come from health care workers, researchers, and others on the frontlines of disease outbreaks who understand the necessity of proper medical countermeasures, like vaccines.

ICT: What initiatives or policies could be implemented to incentivize and accelerate vaccine development for rare diseases?

DT: Policies that support platform technologies that allow you to pivot to new strains of a virus are critical. If you have a platform technology, for example, mRNA, and a new, very different viral strain emerges, scientists can pivot and develop a new vaccine far more efficiently because it would be based on the same platform technology, allowing for "swapping" the original gene sequence with the updated, new gene sequence.

PA: Platform technologies have enormous value in working on families of viruses, especially from a public health perspective. You may focus vaccine development on one virus that has some outbreak potential or even some commercial application. Still, if you see something in the same family that's unknown or a variant of a known, you can use those platform technologies to pivot quickly to develop a new vaccine. In the rare incident space, it's important to focus on the strategy of leveraging platform technologies to do viral family work because they give you a base of knowledge and R&D. So, if you need to suddenly pivot on a dime and make a vaccine for an outbreak or a pandemic within an existing viral family, you can.

We strongly support policies that prioritize this viral family strategy. Several bills before Congress aim to fund this kind of work within the Biomedical Advanced Research and Development Authority (BARDA) and NIH. These bills must be included in the Pandemic and All Hazards Preparedness Act (PAHPA), which is currently under review for reauthorization in Congress.