Taking A Deep Dive With Dr. Phil Dormitzer, Vice President and Chief Scientific Officer for Viral Vaccines at Pfizer
Q. In layman’s terms, what does it mean when you say Pfizer and BioNTech have started a global, barring China, “Phase 2/3 safety and efficacy clinical study to evaluate a single nucleoside-modified messenger RNA (modRNA) candidate from their BNT162 mRNA-based vaccine program against SARS-CoV-2.” In order to be at this stage, what has preceded it?
A. After an extensive review of the available data from our preclinical studies and our Phase 1/2 clinical trials with BioNTech, and in consultation with the FDA, we narrowed down the four vaccine candidates we had been studying and selected one candidate, BNT162b2 at 30 mcg and using a two-dose regimen, to advance into our Phase 2/3 global trial. This portion of the trial will determine if the vaccine candidate protects against COVID-19 disease and provides data needed to file for authorization or licensure of the vaccine by regulators for use in the general public.
This is a major milestone for our development program which began back in April with the launch of a Phase 1/2 trial in Germany and is the culmination of an extensive, collaborative and unprecedented R&D program involving Pfizer, BioNTech, clinical investigators, and study participants with a singular focus of developing a safe and effective COVID-19 RNA vaccine.
Q. What needs to happen in this Phase 2/3 study in order for the vaccine research to advance. What could set it back? What is an anticipated timeline for this phase of the study, what would happen next?
A. In this final phase, we plan to give our potential vaccine to up to 30,000 participants at study sites around the world to test its efficacy and safety.
It’s important to note that there were key considerations we needed to look at when we were developing this study and selecting our sites. We wanted to make sure to enroll a diverse population, including those most at risk for COVID-19 and who may use the potential vaccine, and to enroll participants in areas where there is expected sufficient SARS-CoV-2 transmission so that we can determine if the vaccine is effective at preventing COVID-19.
Assuming clinical success, Pfizer and BioNTech plan to seek regulatory review as early as October 2020.
Q. How do you address fears and concerns that a vaccine is being developed at “Warp Speed,” given the traditional trajectory of a vaccine, and the lack of one for AIDs, to date? In typical vaccine trials, how long is it before scientists can determine possible side effects? Is there concern that there won’t be enough side effect data before vaccine is introduced?
A. The COVID-19 global pandemic represents an unparalleled crisis in recent history and a challenge to science.
Safety was, is and will always be our number one priority in vaccine R&D. We believe that safe and effective vaccines are key to defeating this pandemic and helping to provide protection from this devastating disease. In fact, we started our clinical Phase 1/2 development in a measured and deliberate way with patient safety at the forefront and we selected our go forward vaccine candidate using stringent safety and tolerability criteria.
Even though we are moving with extraordinary speed, preservation of high quality and safety standards is critically important throughout development. We plan to enroll in the Phase 2/3 trial of up to 30,000 subjects, half of them receiving active vaccine. The final number will include enough subjects for a safety database consistent with other large vaccine efficacy trials and vaccines that have received regulatory approvals in the past. What is different this time is that we have mustered enormous resources upfront to enroll participants as efficiently as possible and both federal agencies and Pfizer have been very focused on this vaccine and its progress.
And as in all our work to advance investigational vaccines, we will work closely with clinical trial sites and experienced investigators and regulatory agencies worldwide to ensure high quality and safety standards are applied to our development program. In addition, an independent safety data monitoring committee is in place to evaluate the safety of our vaccine candidate.
Q. How would manufacturing ramp up to make the vaccine accessible to the public, and what does that mean specifically for Pfizer’s Pearl River location?
A. Pearl River is our Vaccine Research and Development hub. It will not play a role in manufacturing the vaccine.
Pfizer is activating its extensive U.S. manufacturing network, including thousands of highly skilled U.S. workers in multiple states and localities, to prepare to produce the COVID-19 vaccine for those most in need around the world.
Assuming regulatory authorization or approval, we currently expect to manufacture up to 100 million doses by the end of 2020 and approximately 1.3 billion doses by the end of 2021, subject to the final dose selection from our clinical trial.
We are investing at risk to do what it will take to bring as many doses of a vaccine forward as quickly as possible. Pfizer anticipates making other (capital) investments over time.
Q. What role, if any, do you think, would be necessary for the government to assume to make the vaccine widely available?
A. Our objective is to ensure rapid uptake and access for patients who will need a vaccine, by ensuring early allocation of needed doses. The allocation of doses to the appropriate populations within a country is a decision for local governments based on relevant health authority guidance. We are committed to working collaboratively with governments to support the public health need, but believe that front line health care workers, essential workers, immunocompromised individuals, and public safety officials should be prioritized consistent with global public health guidelines.
Q. This virus seems to defy a common pathology; it appears to attack so many different parts of the body in so many ways. There’s so much that is still unknown, from how it spreads, whether having it gives immunity, whether someone can be infected more than once. What have you learned from studying the virus as it relates to others viruses? What similarities are gleaned? What makes it unique, and how does that present a challenge for vaccine development?
A. The key reason why COVID-19 rose to pandemic proportions, but other recent coronavirus outbreaks (causing SARS and MERS) did not is that, paradoxically, COVID-19 is less severe.
A lower proportion of those who contract COVID-19 die compared to those who contracted SARS or MERS. When a virus makes a high proportion of infected people very sick, quickly, those infected take to bed at home or in the hospital before they have the opportunity to infect many other people, and the spread of the very severe disease can be contained.
On the other hand, when most people who are infected have relatively mild disease or even no disease at all, they remain out and about, socializing, and potentially infecting others, making the disease difficult to contain.
A special challenge with SARS-CoV-2 (the virus that causes COVID-19) is that, although most of those infected do not get very sick, some people, especially older adults and those in other risk groups, do get very sick and may even die. This combination of mild disease in most people, facilitating spread, and severe disease in some people, causing great harm, has made SARS-CoV-2 a very destructive virus, globally.
We are working at an unprecedented speed – historically, vaccine development for a new pathogen takes many years. This fast pace requires close collaboration among vaccine developers, regulatory agencies, and academic investigators to advance key activities in parallel while continuing to maintain strong focus on safety. Because of the pandemic, we also are quickly increasing our capacity to distribute a vaccine globally, earlier than would typically be seen and at a much greater scale, while maintaining quality control.