The vaccine is here. Three questions about what happens next
Editor’s Commentary: With COVID-19 vaccines on the verge of rollout, policymakers and physicians should brace for a slew of queries
With COVID-19 vaccines on the verge of rollout, policymakers and physicians should brace for a slew of queries about the details.
The COVID-19 vaccine rollout is starting in the U.K., and is on the doorstep in the U.S. and Europe, building to a collective huge sigh of relief. The efficacy, at least for the first two, seems to be in the bag. But with the big issues addressed, questions about the details begin.
While the vaccines’ arrival is unquestionably an astonishing achievement in such a compressed time frame, obtaining regulatory authorization or approval is not the finish line. Getting them to enough people to achieve maximal effectiveness is the goal.
The vaccines’ success will depend not only on how well-thought-out the distribution is, but on how much governments and industry can learn on the fly to respond in real time to needs and data as they arise.
Next week, the U.K. will start vaccinating its highest priority group — residents and staff in care homes for older adults — with BNT162b2, the COVID-19 vaccine from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX) that received MHRA authorization Wednesday.
If ever there was a time for real-world data to step into center stage, this is it.
Within a few weeks, it’s likely the U.S. will start deploying the same vaccine, along with mRNA-1273 from Moderna Inc. (NASDAQ:MRNA), which will be discussed at FDA advisory committee meetings on Dec. 10 and Dec. 17, respectively.
Europe is fast on their heels, with CHMP scheduled to complete the review of the Pfizer-BioNTech and Moderna vaccines at extraordinary meetings on Dec. 29 and Jan. 12, respectively. If CHMP recommends approval, the EC has committed to accelerate its process to approve the vaccines within days.
At least one or two of the other front-runner vaccines will likely follow shortly.
AZD1222 from AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and the University of Oxford is under review at MHRA, and JNJ-78436735 from Johnson & Johnson (NYSE:JNJ) could receive emergency use authorization (EUA) from FDA in February, according to Moncef Slaoui, chief scientific adviser of the U.S. government’s Operation Warp Speed.
The U.K. has defined its order of priorities for distributing the vaccine, and CDC’s allocation will follow the same or similar lines.
So the top question, “when will I get it?” will be answered soon. Here are three of the next ones.
Question 1: Is there a comprehensive plan to track outcomes among people who have been administered the vaccine?
If ever there was a time for real-world data to step into center stage, this is it.
The information gained by tracking outcomes is not only important for learning about adverse events, but for understanding demographics of uptake and responses, how long immunity lasts, and how these factors vary between the different vaccines being deployed.
It’s unlikely individuals will get a choice if multiple vaccines are approved, but to understand the true effectiveness of each product — which is defined at a population level — a national if not global system to track outcomes will be imperative.
The U.K. has an inbuilt registry via its NHS system, which could massively facilitate the logistics of distributing the vaccine, but it’s not clear to what extent the country will use that asset to track outcomes.
In the U.S., plans for some form of registry are under way. On a Dec. 2 call with reporters, Slaoui said FDA and CDC are working to put together a pharmacovigilance and surveillance system using existing databases, and will be able to integrate information from Medicare, the U.S. Veterans Affairs Department and insurance carriers.
Still, distribution of the vaccine will be handled at a state level, and if the COVID-19 public health strategies are anything to go by, the chances of a uniform system are pretty low. Many individuals may get the vaccine outside of insurance carriers, including members of minority communities who are already disproportionately affected by the disease.
A fractured distribution system and a lack of insurance coverage for many individuals will make pulling off a nationwide surveillance system that much harder.
The biology of COVID-19 is still unfolding. New features of its pathology continue to be uncovered, and the advent of vaccines may elicit more unknowns. Failure to track problems and respond in real time will hamstring the effort to properly attack this disease.
Question 2: If you receive a vaccine that is 70% effective, will you be able to find out if you responded, and if not, can you get one of the other vaccines?
The AstraZeneca vaccine appears to be 62-90% effective, depending on the dose, and it’s highly possible that other candidates may fall short of the 95% efficacy reported by Pfizer and Moderna for their respective products.
That may increase demand for the Pfizer and Moderna vaccines, but not everyone will be able to receive them.
Pfizer’s BNT162b2 and Moderna’s mRNA-1273 are both mRNA-based vaccines. Together, they represent 25% of the 800 million vaccine doses procured by Operation Warp Speed, and 13 % (47 million doses) of the U.K.’s vaccine war chest. By contrast, AZD1222 represents about 37% of the OWS procurement, and 28% of the U.K.’s.
The balance consists of non-mRNA modalities, and it’s anyone’s guess where they will fall in the efficacy spectrum.
Strategies to ensure all sectors of the population have access to a vaccine are not enough; equity must extend to outcomes.
J&J has a viral vector-based vaccine, the same modality AZ has chosen; Novavax Inc. (NASDAQ:NVAX) has a protein-based vaccine, as have partners Sanofi (Euronext:SAN; NASDAQ:SNY) and GlaxoSmithKline plc (LSE:GSK; NYSE:GSK); and Valneva SE (Euronext:VLA), which has secured a commitment for 60 million doses from the U.K., has an inactivated whole virus vaccine.
AZ’s efficacy easily clears the 50% bar set by FDA for EUA, and falls well within the range of other vaccines, such as the flu vaccine. At a population level, this means that with time, if there is broad uptake, these COVID-19 vaccines could allay the disease, meaning, most likely, downgrade it to endemic status.
But on an individual level, if a person does not respond to the vaccine, they remain vulnerable to COVID-19. Persuading people to take a vaccine that is inferior to others that are available, without recourse to take the better one if needed, could precipitate an avalanche of problems in public trust — which will translate to lower uptake.
There’s little information about what activities are taking place to ascertain who among recipients will have responded. And if there is an option for individuals to receive a second, different, vaccine, surveillance will be needed to identify safety issues that could arise from following one vaccine with another.
Again, the registry and real-world data will be important here.
Equally important will be to ensure there are therapies available — free to the patient — for vaccinated individuals who don’t respond and develop severe disease.
Strategies to ensure all sectors of the population have access to a vaccine are not enough; equity must extend to outcomes, and ensuring all individuals can be COVID-free is the goal.
The U.S. government has laid the groundwork, with Operation Warp Speed covering costs for the antiviral Veklury remdesivir from Gilead Sciences Inc. (NASDAQ:GILD) as well as the antibody cocktails from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Eli Lilly and Co. (NYSE:LLY). The mAbs in particular are limited in supply and require infusion, making them complex to administer on a mass scale.
The national stockpile will need to extend to other agents in development for COVID-19. Hundreds are in development, and with more than 100 possible Phase III readouts by 2Q21, there’s reason to hope some will lead to alternative and better options.
Question 3: Will people who have had symptomatic COVID-19 get the vaccine as well?
Plans are under way to triage the population by risk, but it’s not clear if people who have had COVID-19 will automatically receive the vaccine along with their respective risk tier or demographic group, or if they will be deprioritized to let people who likely have zero immunity go first.
Many patients who have recovered from COVID-19 will likely have high antibody levels, though little is known about the longevity of disease-induced immunity, or how it differs from vaccine-induced immunity.
Nor is it known how the vaccine would work in individuals who already have high antibody levels, because the clinical trials for the front-runner vaccines tested for SARS-CoV-2 positivity on enrollment, but not for antibody levels.
While serology tests can determine previous exposure, they aren’t sufficiently reliable to rule anyone in or out for receiving a vaccine. The Infectious Disease Society of America recommends the tests’ use for serosurveillance at a population level to track the disease, but has stated that there is not enough evidence from them to infer protection.
Will individuals be asked to disclose if they previously had the disease to receive a vaccine?
If the vaccine has no added benefit to a recovered patient, the only downside is the use of a scarce resource that could have gone to a vulnerable individual. But if the vaccine causes harm in those individuals the consequences are not only terrible for the patients, but could amplify resistance among vaccine skeptics.
Signed commentaries do not necessarily reflect the views of BioCentury.