The webinar featured:

• Kelly L. George, Consultant II, Commercialization & Regulatory Strategy
• Richard Hughes IV, Managing Director, Vaccines Leader
• John C. Neal, Managing Director, Commercialization & Regulatory Strategy
• Elizabeth Carpenter, Head of Advisory Services, Policy

The pipeline for COVID-19 vaccines and therapeutics has grown rapidly since the beginning of 2020, with over 500 products currently in development. An existing body of research on coronaviruses and experience with other diseases like MERS and SARS have facilitated the advancement of potential therapeutics and vaccines. Traditional therapeutic and vaccine development can take 10–15 years from preclinical stages to approval, but previous basic research on coronavirus along with the availability of newer technologies and compression of development activities has expedited the process. As several candidates enter phase-3 trials and other existing products are repurposed for COVID-19, challenges in pricing, distribution, and access may arise.

FDA Regulatory Considerations

At the beginning of the pandemic, the Food & Drug Administration (FDA) attempted to strike a balance between reducing regulatory barriers to the development of products to combat the SARS-CoV-2 pandemic, continuing regular product development for other important diseases and conditions, and maintaining routine regulatory activities to protect public health. This has been a difficult situation and one that FDA, like all of us, has been able to improve on as more data have been aggregated, allowing for science-based decisions and policies. In the months that followed, COVID-19 data accumulated and allowed the FDA to release increasingly clear guidance for human clinical trials. The FDA has collaborated with manufacturers to shorten the therapeutic and vaccine development timelines with initiatives such as rolling reviews, clear guidance, and increased access to agency personnel. Academics, policymakers, and manufacturers have also created public–private initiatives to speed development of promising candidates by coordinating and leveraging assets, information, and tools. As products move through clinical trials, manufacturers will need to think about the regulatory pathway they wish to pursue. One of these routes is an Emergency Use Authorization (EUA), which is a temporary authorization able to be obtained before a full FDA approval. The agency is ultimately responsible for deciding which COVID-19 products can go to market, and most decisions will depend on a products’ risks and benefits. To issue an EUA, a product must meet the statutory requirement of “may be effective” rather than the substantial effectiveness that is necessary for a full approval. To meet the clinical need in absence of a fully approved COVID-19 treatment, the FDA has issued 2 EUAs for therapeutic products, 1 of which was later revoked. In the case of vaccines, the risk–benefit profile presents a more challenging analysis for the agency given the indicated population would likely be in good health. It is expected that an EUA will only be granted to a vaccine once substantial evidence of safety, efficacy, and quality can be shown.

Coverage and Access Challenges

The US government expects to deliver 300 million doses of a vaccine by early next year to vaccinate all Americans. Dubbed “Operation Warp Speed,” this initiative has involved contracting with developers to create a plan for dose procurement. Several candidates are in phase 3 of clinical trials, any of which could receive an EUA. In the coming year, more candidates could receive licensure and support widespread vaccination. However, that many doses would require scaling efforts and robust infrastructure to support development. In response, investments have been made in alternative modes of administration (e.g., orals, injectables). Manufacturers are also looking to partner with companies across borders to support product development and technology transfer.

Once vaccines do come to market, they will not initially be available to the general public, and the prioritization of populations will be required. An important consideration is allocation within the US and across other countries. Anticipating high demand and limited supply, discussions have been ongoing on how to prioritize populations. When a product receives licensure, it will be centrally distributed in a phased approach to ensure the most vulnerable receive it first. As more vaccines and therapeutics become available, the government’s role in procurement and distribution will wane. The timing for launch and patient access is very fluid.

Pricing, Procurement, and Distribution Scenarios

With vaccines and therapeutics on the horizon, product distribution has been a key consideration. Several organizations have developed distribution frameworks, including the ACIP COVID-19 work group and Health & Human Services (HHS). Historically, the government decides distribution in situations where product supply is limited and far exceeds demand, especially during public health emergency situations. While the Centers for Disease Control and Prevention has significant experience in nationwide vaccine purchasing, distribution, and collaborating with states on planning and dissemination, the Department of Defense is anticipated to play a strong role in vaccine distribution. The vaccine distribution process and access will likely vary by state because of differing priorities and infrastructure.

The scenario is different for therapeutics, given fewer historical precedents, and will vary on whether it is a new product (e.g., Remdesivir) or an existing product with a new indication or EUA (e.g., hydroxychloroquine). For products already available to consumers, distribution and utilization is difficult to control and usage is largely determined by public health messaging. With several indications, a product shortage can have severe consequences for patients prescribed the product for another condition. Distribution of new products is less straightforward, with Remdesivir being the only example. Remdesivir’s EUA specified that the product will only be distributed to locations at the direction of HHS.

In terms of pricing, Institute for Clinical and Economic Review (ICER) has been active in developing a pricing framework. ICER’s analysis will be important for manufacturers determining the value of a vaccine, including unique considerations like public benefit. Another aspect of pricing is reimbursement, which is critical to prevent health system burden. Manufacturer experience and the competitive landscape will also play a part in pricing. While the government will likely set the list price, many factors that will impact pricing (e.g., demand, disease burden, efficacy) are still evolving.

View “Cutting Through the Noise: Market Evolution and Pathways to Access for COVID-19 Vaccines and Therapeutics.”