COVID-19 update: Your latest questions about Johnson & Johnson’s investigational vaccine candidate answered
With its Phase 3 clinical trial now fully enrolled, the Global Head of Research & Development at Janssen brings us up to speed on the progress of the company’s vaccine candidate, including upcoming key milestones.
Johnson & Johnson is one of many companies hard at work on an investigational COVID-19 vaccine candidate—work that included recruiting adults of all ages and ethnicities for a Phase 3 clinical trial known as ENSEMBLE, which is now fully enrolled with approximately 45,000 participants.
Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson, has been helping to spearhead these efforts since last January. His goal: ensure a safe, effective and easily distributed and administered vaccine is accessible at scale for people around the globe.
With company scientists anticipating efficacy and safety data for this trial for review by the end of this month, we sat down with Dr. Mammen for an update on his team’s latest research and development milestones as they work toward a once-in-a-century public health achievement.
It can take years to develop a vaccine. How were scientists at Janssen able to mobilize so quickly?
The unprecedented speed of our vaccine development was dependent upon several things: collaborations and partnerships with government, regulatory authorities and the scientific community around the world, both in terms of funding and pooling knowledge; our ability to streamline the production process based on past experience with vaccine development; and our ability to invest at scale well ahead of clinical studies. Unfortunately, the fact that the virus has been circulating so abundantly in the world also made it possible to test the vaccine candidate against COVID-19 substantially faster.
Last January, we obtained the novel coronavirus’ sequence information from China—that is, information about its genome, or genetic material—and validated it.
Due to our extensive previous experience with vaccine technology—we used the same technology to create our European Commission-approved Ebola vaccine—scientists already had a good sense of the best doses to use for the investigational COVID-19 candidate.
From there, we collaborated closely with Dan Barouch, M.D., Ph.D., and his team at the Center for Virology and Vaccine Research at the Beth Israel Deaconess Medical Center, an affiliate of Harvard Medical School, to design a large number of potential candidates for the vaccine. We had previously collaborated with Dr. Barouch on preclinical work for our Zika and HIV vaccine candidates.
We also partnered with the Biomedical Advanced Research and Development Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, to commit equally to more than $1 billion to cofund research, development and clinical testing for a potential COVID-19 vaccine.
From March to June, we experimented with various candidates, whittling the field down to two in June—and finally getting it down to one in July.
We then combined the traditional first two research phases of a clinical trial into one phase, known as Phase 1/2a, so we could examine our candidate’s safety and immune response within a couple of months. A traditional approach may have taken up to a year.
This was possible, in part, because our discovery and manufacturing teams were able to execute several steps in parallel that they normally would have executed sequentially. And due to our extensive previous experience with vaccine technology—we used the same technology to create our European Commission-approved Ebola vaccine—scientists already had a good sense of the best doses to use for the investigational COVID-19 vaccine candidate.
Once we had strong interim data from the Phase 1/2a trial, we were able to move into Phase 3 clinical trials with a chosen dose. During Phase 3, many more people receive the vaccine to thoroughly test safety and efficacy. And the more people who can be vaccinated at this point, the sooner researchers can gather conclusive results.
How is your Phase 3 single-dose ENSEMBLE trial going?
It’s proceeding very well. We began recruiting participants for it at the end of September, once we got the Phase 1/2a data in.
We used extensive disease modeling and simulation from our data science team, in partnership with MIT, to predict where COVID-19 incidence at a regional level would be highest, and where the populations we wished to focus on were based. We picked our trial sites based on this Janssen-MIT machine learning model, and have benefited significantly in speed from these choices.
The trial is now fully enrolled with roughly 45,000 adult participants. In fact, ENSEMBLE is the fastest enrolled trial in Johnson & Johnson history—we secured these participants in less than four months.
A lot of effort was also put toward ensuring all races, ethnicities, ages and medical backgrounds are represented in our clinical trials. While diversity is important in all of our research at Janssen, it’s especially crucial for the investigational COVID-19 vaccine, because the virus disproportionately affects Black and Latinx communities, for example. So we have been committed to ensuring that these populations are well represented in our clinical trials.
Our site selection model was very important in placing us in areas of high diversity for this clinical trial. We then employed a large number of methods to ensure that we pulled through diverse participants.
Our ENSEMBLE study protocol includes both 14-day and 28-day endpoints. (Endpoints are the primary outcomes being measured in a clinical trial, like physical symptoms or test results showing protection against disease.) Our expectation is that full immunity is reached after day 28, and that we may see some protection as early as 14 days.
As of today, all participants have been randomized to receive either one dose of the vaccine or a placebo. The next step in the process is to review the efficacy and safety data from that trial, which we anticipate receiving by the end of this month. As an “event-based study,” meaning that we need a certain number of randomly occurring events to occur prior to analysis, the exact timing of when we will see data is somewhat uncertain.
You are also studying a two-dose regimen. Can you tell us more about this?
At Johnson & Johnson, we’re extremely thorough and driven by science. The ENSEMBLE 2 study, which we’re now recruiting for, will give participants two doses of the vaccine spaced two months apart. The reason we are running this second study is to see if a second dose might provide greater, or longer, protection.
What percentage efficacy are you looking for?
COVID-19 vaccine manufacturers are reporting efficacy rates greater than 90%, and we too would like high efficacy.
We do have long-term safety data for our vaccine platform; more that 140,000 people have received vaccines and vaccine candidates using the platform.
And we feel very confident in our one-dose regimen. Since we spent so much time and effort in zeroing in on one specific antigen, we were able to optimize it and make it as strong as possible.
Can you tell us more about how your investigational vaccine works?
Unlike mRNA vaccines, which use messenger RNA to create a protein that prompts an immune response in the body, our investigational COVID-19 vaccine uses an adenovirus—a type of virus that causes the common cold—that has been made unable to replicate. The adenovirus carries a gene from the coronavirus into human cells, which then produce the coronavirus spike protein, but not the coronavirus itself. This spike protein is what primes the immune system to fight off a subsequent infection by the virus.
There are a couple advantages to this approach. First, the adenovirus is well known in the human population. And we’ve used it before, in our Ebola vaccine and in investigational vaccines for HIV and RSV, so we have a lot of long-term safety data for it.
Secondly, it helps make a vaccine temperature stable.
The vaccine technology we’ve used can remain stable for two years at -4° F, and at least three months at 35-46° F, which is about the temperature of your home refrigerator. It may be stable for even longer at refrigerator temperatures, and we are actively collecting stability data now to see how long we can go. We believe this stability will help make it easier to transport and distribute our COVID-19 vaccine candidate without the need for shipping at special temperatures.
What are the next key milestones for your vaccine candidate?
Once we receive efficacy and safety data from our Phase 3 study, which should come in later this month, we’ll be looking for very specific endpoints.
We’re hoping these milestones can come together by February, so that we can then consider applying for an emergency use authorization of our vaccine with the FDA, as well as regulatory filings in other countries.
Our endpoint looks at whether our investigational vaccine prevents someone from getting sick with moderate to severe COVID-19—meaning they show at least two symptoms, such as a fever and cough—as well as if that person has a positive PCR test, which detects the virus’ genetic material. We measure this at different timepoints to see when the protection will kick in.
The other big milestone is manufacturing. We need to ensure all aspects of our COVID-19 vaccine development program meet our safety and quality standards, and that all of our manufacturing and distribution processes comply with all applicable regulations. This includes our raw materials and other components; procedures; manufacturing facilities; testing laboratories, including equipment and analytical methods; shipping and routes; and shelf life and stability.
We’re hoping these milestones can come together by February, so that we can then consider applying for an Emergency Use Authorization (EUA) of our vaccine with the U.S. Food and Drug Administration (FDA), as well as regulatory filings in other countries.
We’ve committed to not-for-profit pricing during the pandemic period if we are granted EUA (or its equivalent) in any region of the world. We want to bring an affordable vaccine to the public, with the goal of providing 1 billion doses in 2021 and more after that.
What do you personally think is most remarkable about the race to create a potential COVID-19 vaccine?
The devotion of every single person involved in these clinical trials.
There are so many employees who are pouring immense creativity into this program and working nonstop as part of the effort to deliver a vaccine at record speed. I also have immense gratitude for our study investigators and coordinators, nurses and other frontline healthcare workers.
I have also been very pleased with the collaboration across our industry. I led a vaccine group under the COVID R&D Alliance in which different organizations helped one another in all sorts of ways, and ensured that the industry was going to deliver a definitive solution to this pandemic. I have never seen such collaborative behavior across companies in my career.
On a final note, I have so much admiration and respect for all the people who have signed up to be in our clinical trials. They wanted to help wage the war against COVID-19 and make our world a safer, better place. They are heroes.