As the COVID-19 pandemic continues to challenge humankind worldwide, the medical industry and professionals alike are developing vaccines at lightspeed, hoping that they can offer an exit strategy that will last.
Recent news regarding COVID-19 vaccine development is certainly a shining light on some dark times this year, but much remains to be accomplished. We spoke with our experts about next steps in the vaccine development journey and what the results from Moderna and Pfizer mean for vaccine development as a whole.
Pfizer and Moderna are two drug development companies who have surged ahead with mRNA-based vaccine development, achieving 95% efficacy in reported analyses of their studies. An mRNA vaccine involves a person receiving an injection of genetic material that encodes a viral protein, instead of just the protein injection like with other vaccines. mRNA can most easily be described as instructions for the cell on how to make a piece of the “spike protein” that is unique to the COVID-19 virus. That protein causes the immune system to begin producing antibodies and fight off what it thinks is an infection.
As Pfizer and Moderna move forward to bring their vaccines to the public, they are now applying for Emergency Use Authorizations (EUAs) with regulatory authorities in the US and Europe.
It’s important to recognize that in nine months—not years, which is how long vaccine trials typically take—humankind came up with a strategy to develop a vaccine. Experts at Pfizer and Moderna used their knowledge and expertise to develop a vaccine, test it, and submit it for approval. This is truly groundbreaking, as it has never happened in the history of vaccine development.
This news is certainly a shining light on some dark times this year, but the vaccine journey is not over. We spoke with the following experts about next steps in the fight for a COVID-19 vaccine:
- Lynlee Burton, Exec Director and Head: Center for Vaccine Research
- Darin Seehafer, Senior Director of Therapeutic Expertise - Vaccines
- Jay Lieberman, M.D., Medical Director
- Mark Lane, Exec Director, Global Drug Development
- Elizabeth Harrison, Project Manager, Medical Informatics
The question on everyone’s mind: Is 95% efficacy “good”? What can we compare it to/what context can we consider in evaluating?
JL: It’s not just good—it's extraordinary. There was no guarantee when vaccine development for COVID-19 began that an effective vaccine could be found, because we still don’t have effective vaccines for other respiratory tract pathogens that have been known for much longer. It’s remarkable that we will have effective vaccines available soon. The expectation of efficacy was much lower than 95%.
DS: A few months ago, Anthony Fauci went on record saying that 50 to 65% protective efficacy would be considered a win. When Moderna and Pfizer’s data was released, we were all excited by how they exceeded those expectations.
In less than a year, we’ve experienced sequencing of the COVID-19 virus to almost certain vaccine approval. This would usually take much longer. Do you feel this sets a precedent for changes in drug development timelines?
DS: The global consensus is simply that a vaccine needed to happen. With that consensus came funding. Often, funding really does dictate the pace of research, but this is just one out of many factors as each case needs to be evaluated on an individual basis. That said, just because you can do something faster doesn't mean you should. I believe aspects of our industry will forever change in how quickly we do studies.
COVID-19 by its very nature forced sponsors to start accepting integration of technology into clinical trials. That means we’re able to do new things that we couldn’t do before—for instance, the use of Decentralized Clinical Trial designs using innovative Digital Health Technologies. We’re seeing the benefits of operating remotely and having telehealth visits with physicians. This is going to be key as we start to think about who these vaccines benefit. The only way you're going to reach those underserved populations, for example, is with a decentralized model.
LB: The world learned an important lesson from Ebola and responded with the help of organizations like CEPI to support companies, allowing them to prioritize research in diseases that are devastating many parts of the world. As a result, companies with the right technologies were able to respond to COVID-19.
ML: I think you may see companies taking a few more risks and being more innovative in their development programs utilizing technology (i.e., not using paper patient diaries but using online patient diaries) and doing appropriate activities in parallel. We’re definitely at the beginning of a shift in thinking.
DS: I think COVID-19 shines a light on the need to consider new platform technologies. There’s been 1.4 million total COVID-19-related deaths to date. Yet, there's 1.4 million people that die every year from TB, but it's not considered a pandemic. CRO investment into emerging infectious diseases, along with technological capabilities, are what will put our industry at the forefront of this arena.
What do development timelines typically look like for comparable types of vaccines? How does this stack up to other major vaccines from the last several decades, and why/how might COVID-19’s timeline be faster?
LB: mRNA technologies, which were used to develop Moderna and Pfizer’s vaccines, have been around for decades, but there has never been a vaccine approved using mRNA technology. mRNA doesn’t require the vaccine company to actually have access to the live virus. This is a major milestone in the vaccine field.
However, with mRNA, COVID-19 vaccines can be designed using the genetic code that was released by China on January 12, 2020. The genetic sequence was available to anyone who wanted it via the internet and with the new technologies – that was all they needed. By February 24, Moderna had a vaccine candidate.
The typical technology required for obtaining a virus and weaking/inactivating it can take years. This is not necessary for mRNA. For the Moderna study, human studies began the same day animal studies started. The Oxford vaccine was built on research from the 2000 SARS and MERS outbreaks.
Through Operation Warp Speed, the US government decided to provide funds to manufacture large quantities of the vaccine at risk. This is almost never done. This was a public health emergency measure to respond to the situation, keeping in mind all of us. Pfizer is saying that the day they get the Emergency Authorization, they will be able to ship the vaccine either that day or the next. Funding was not an issue or a roadblock. CEPI (Coalition for Epidemic Preparedness Innovations), along with other foundations and governments provided funding early on in the pandemic and then regulatory agencies expedited approvals.
Pfizer’s current trial is a combined Phase I/II and III trial, which allows the company the flexibility to keep moving once they have supportive data. The pandemic demanded a global need for a vaccine, and that need was supported by people around the world. COVID-19 was a global priority, so governments had to respond.
DS: Typically, clinical studies run along three phases for licensure, along with a fourth phase for post licensure. Each phase can take several years, and to date the fastest a vaccine to ever be licensed was the mumps vaccine, which took four years.
What was done differently for COVID-19 was the phases were combined, i.e. Phase I-II or Phase II-III. This, along with adequate funding to prebuild a manufacturing infrastructure and digital gene sequencing, shaved significant time off the standard research timeline. This strategy didn't decrease the number of subjects that were needed for these studies. It didn't cut out the safety follow-up aspects or anything with regards to safety. It simply allowed the studies to move forward faster.
When you look at the historical frequency of past pandemics, you can see that they have become more frequent as you reach the present. While we certainly cannot understate just how serious the COVID-19 pandemic has been, it’s actually given the world time to get prepared for the next pandemic, which could be far worse and spread much faster. Therefore, we must use COVID-19 as a learning opportunity for possible future pandemics.
Disease X is hovering out there. It will happen again at some point, and we have to be prepared for it. We must have systems in place and be able to stand-up studies extremely fast.
The vaccine was submitted for Emergency Use Authorization (EUA). What is the difference between EUA and full approval? What, if any, are the implications of the vaccine not having full approval yet?
JL: Emergency Use Authorization allows unapproved medical products or unapproved uses of approved medical products to be used in emergencies. For this pandemic, this has already been used to authorize diagnostic tests and certain therapies. These processes operate under a different levels of stringency than would normally be used for medical products.
In an emergency and compassionate use, the benefits are perceived to outweigh the risks, and an EUA allows its use in this pandemic. Vaccines, because they are given to people who are not sick, are held to a higher standard than a therapy for patients who are ill. For vaccines, there's still a high standard to demonstrate safety and efficacy, but the evaluation is done in an expedited timeline. The longer-term safety evaluation to assess for the potential for much rarer adverse events will have to wait until the vaccines are licensed and used more widely. If there were adequate vaccine supply, they would be available for everyone. But with limited supply, the initial focus will be on those who would derive the greatest benefit or are at greatest risk of disease.
LB: EUA has been used for COVID-19 testing and treatments. The drug must be determined as safe to use and beneficial. In addition to that, it must meet a specific set of criteria. Still, we must emphasize that the risk is worth the benefit of putting that vaccine out there. Overall, the FDA is looking for enough safety data to warrant the risk of using those vaccines in an emergency situation for medical professionals and at-risk populations.
Pfizer submitted interim results once they had the right number of COVID-19 cases. In case-driven studies like Moderna and Pfizer’s, they give all of their study participants the vaccine or placebo and then wait for COVID-19 cases. Once they have a statistically determined number of COVID-19 cases, statisticians will compare the number of cases which occurred in the placebo group to the vaccine group to determine efficacy. It is important to note that the clinical trials will continue after the EUA is granted to continue to collect safety and efficacy data.
What changes in regulatory legislation, technologies, collaborative efforts, and innovative methods have helped expedite development of these vaccines?
JL: Technology is a huge part of this vaccine development. For a long time, there were limited ways to make vaccines. In general, a vaccine either was killed/ inactivated or a ”weakened” strain of the virus or bacteria.
Over the past few decades, we’ve gained a greater understanding of the immune system and how to elicit a protective immune response. Until now, there were no mRNA vaccines that had ever been licensed. Through these vaccines, we’re now seeing the fruits of extensive research efforts. As soon as the genetic sequence of SARS-CoV-2 was released, companies got to work in developing vaccines.
LB: Researchers’ experience with SARS-CoV-1 and MERS-CoV, which were also both coronaviruses, helped in the fight against COVID-19.
How do you think we’ll study the effects of COVID-19 vaccines in the real world, once a vaccine is widely administered?
LB: Post authorization safety surveillance will be just like what our Real World Solutions team does all the time. They conduct post-marketing studies, where they continue to study the vaccine or the drug once it becomes approved and gets distributed to the general population.
EH: There are a number of things PRA specifically is doing to study the effects of COVID-19 in the real world. These will certainly continue even after a vaccine is distributed. For instance, PRA can leverage our US patient real world data that covers over 300 million active patients across all diagnoses, with over 90% coverage of prescriptions dispensed. This data is geographically representative and covers all payers (Medicaid, Medicare and Commercial Insurers).
In addition, PRA has been tracking COVID-19 diagnosis, testing, and treatment information on a weekly basis. Once a vaccine is approved, PRA will assess the patients that received a vaccine and track them forward in time. We can evaluate if they received a COVID-19 diagnosis, as well as other conditions like sepsis, respiratory failure, and pneumonia. PRA continues to provide weekly updates of flu seasons and flu vaccines, which will prove critical to understand amongst the COVID-19 pandemic happening simultaneously.
JL: There’s nothing new here. For any new medication or vaccine, the FDA requires long-term studies to further evaluate its safety and real world effectiveness.
DS: COVID-19’s epidemiology will be monitored as it continues to evolve or fall off overtime. There's a certain percentage of the population that must receive the vaccine in order to have herd protection. Those numbers range depending on the efficacy of the vaccine, but usually 65-70% of the population must be vaccinated in order to see a significant reduction in disease.
There are now 7.5 billion people on the planet. There will need to be a lot of doses in many arms in order for us to control the spread of the disease. It’s obviously not going to happen overnight. This is going to take time, especially given the potential vaccine hesitancy that some people may have.
Together, we must figure out how to advocate strongly for this vaccine. Saying it’s safe and that no corners were cut will not be enough. We must continue to be transparent with safety data and help those who are hesitant to understand the role they play in getting vaccinated.
COVID-19 has amplified the challenges our industry is currently facing.
We’re leveraging our entrepreneurial mentality, agile infrastructure, data-driven insights, and patient-centric approach to transform clinical research in a world shaken by COVID-19. The work we do has a global impact. We’re fully committed to making it a positive change worldwide.
CRISPR-Cas9: Hot Topic, Proceed with Caution
International Master’s Program Prepares Doctors, Scientists, Researchers for Careers in Vaccines, Drug Development
Siena, a city in Tuscany, Italy and capital of the province of Siena, is one of the nation's most visited tourist destinations, known for its…