How Much Data Is Enough To Approve A COVID-19 Vaccine?
Speakers Moderator Panelists Sarah Karlin-Smith Jonathan Ellen Holly Fernandez Lynch Senior Writer, Pink Sheet Epidemiologist & Former John Russell Dickson, MD Hospital CEO And Vice Presidential Assistant Pharma Intelligence Dean Professor of Medical Ethics Manhattan Institute University of Pennsylvania informa | Pharma Intelligence 2
FDA Guidance Traditional Approval Leads The Way “At this time, the goal of development programs should be to pursue traditional approval via direct evidence of vaccine safety and efficacy in protecting humans from SARS-CoV-2 infection and/or clinical disease.”
Traditional Approval Endpoint: The primary efficacy endpoint for a placebo-controlled trial should be at least 50%. Encourages standardization of endpoints across trials to allow for comparison of vaccines. Design: RCT, Double blind, 1:1 Randomization preferred, Potential to evaluate multiple vaxs against one placebo arm. Eventually could do non-inferiority studies with vaccine control. Safety: Pre-licensure safety database of at least 3,000 study participants vaccinated with the dosing regimen intended for licensure. Need to assess the risk of vaccine-associated enhanced respiratory disease (does vaccine make end up making worse?) Post- licensure: Evaluate serious adverse events at least six months post trial, longer if new vaccine technology. informa | Pharma Intelligence 4
We felt like this was a reasonable place to go. Can we show you some calculation of how we got there? No. If you go much lower than 50%, …vaccines may have very little efficacy. If we held that number at 70% or 80% ….we may not have a vaccine until there’s actually herd immunity that’s occurred naturally. Peter Marks Director of the Center for Biologics Evaluation and Research (CBER) at the FDA
Phase III Population • Thousands of participants, including many with medical comorbidities • Acceptable safety database for younger adult and elderly populations • Encourages enrollment of populations most impacted, specifically racial and ethnic minorities • Consider including pregnant women and women of childbearing potential • Children? • Do not need to exclude participants with history or laboratory evidence of prior SARS-CoV-2 infection. Individuals with acute COVID-19 (or other acute infectious illness) should be excluded. informa | Pharma Intelligence 6
Vaccine trials will aim to enroll 30,000 participants. …It will only take about 126 episodes where somebody with the placebo gets infected and somebody with the vaccine doesn't to know that this has worked. ….The reason to prolong the study, after that has already been achieved is…Are there any long term side effects that weren't anticipated? …And also how durable is this particular immunity? Is this vaccine going to be something that works for life or will you need a booster in a year or two. Francis Collins Director of the National Institutes of Health (NIH)
Accelerated Approval – Not So Fast • Need additional understanding of SAR-CoV-2 immunology and vaccine immune responses that might be reasonably likely to predict protection against COVID-19. • Because its novel pathogen, a surrogate endpoint reasonably likely to predict protection from COVID- 19 should ideally be derived from human efficacy studies examining clinical disease endpoints. • A potential surrogate endpoint likely would depend on the characteristics of the vaccine, such as antigen structure, mode of delivery, and antigen processing and presentation in the individual vaccinated. informa | Pharma Intelligence 8
Challenge Studies Guidance: However, If it is no longer possible to demonstrate Many issues, including logistical, human subject vaccine effectiveness by way of conducting protection, ethical, and scientific issues, would need clinical disease endpoint efficacy studies, the to be satisfactorily addressed. use of a controlled human infection model to obtain evidence to support vaccine At this time no controlled human infection models for efficacy may be considered. SARS-CoV-2 have been established or characterized. informa | Pharma Intelligence 9
Right now it gives people some ethical heartburn and scientifically it’s complicated. That being said … our current thinking is, it’s something that we would consider depending on what was put in the protocol and given the circumstances. … It’s not a no. It’s a we’ll see what you submit. Peter Marks Director of the Center for Biologics Evaluation and Research (CBER) at the FDA
Marks On The Challenges With Challenge • We don’t have something that cures 100% of the time or near 100% of the time. • Some people have a very mild illness, other people get a very serious illness and we don’t understand enough about why this happens. • Where do you keep people during trial? • What strain do you use for the infection and how much of it do you give. • If we have monoclonal antibodies that are really good at shutting down disease, that could be a game-changer for challenge studies informa | Pharma Intelligence 11
Emergency Use Authorization – High Bar Standard: Known and potential benefits of a product outweigh the known and potential risks of the product. Reality: EUA for COVID-19 vaccine would likely look closer to a traditional approval in terms of clinical trial data needed. “Issuance of an EUA for a COVID-19 vaccine prior to the completion of large randomized clinical efficacy trials could reduce the ability to demonstrate effectiveness of the investigational vaccine in a clinical disease endpoint efficacy trial to support licensure, and such clinical disease endpoint efficacy trials may be needed to investigate the potential for vaccine-associated ERD.” Manufacturing : Potential for speed might be on manufacturing review “For a vaccine for which there is adequate manufacturing information, issuance of an EUA may be appropriate once studies have demonstrated the safety and effectiveness of the vaccine but before the manufacturer has submitted and/or FDA has completed its formal review of the biologics license application.” informa | Pharma Intelligence 12
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