In the early part of 2016, headlines were dominated by the Zika outbreak in large parts of South America. Linked to birth defects, the Zika virus is believed to cause microcephaly, a condition affecting brain development. As concerns over the outbreak have risen, the pharma industry stepped up efforts to find a vaccine to combat the virus.
CTA spoke to Joel Maslow, Chief Medical Officer of GeneOne Life Science. As part of the company’s Zika vaccine trial, being conducted in collaboration with Inovio Pharmaceuticals, GeneOne is running the first and second first-in-man trials to assess the safety and immunogenicity of the vaccine. In this interview, Maslow explains the challenges in conducting the vaccine trial.
Clinical Trials Arena: What challenges have you faced in getting this trial off the ground?
Joel Maslow: Unlike many other diseases that people have gone to develop vaccines or therapeutics for, Zika had a dearth of information. There was no information to allow us to know the correlates of protection, meaning what kind of immune response is needed to have protection. There was little information as far as understanding the epidemiology and there had been no work up until the latter part of last year on developing a vaccine.
And so what all of the vaccine manufacturers had to do, and what we did, was that all the necessary parts in vaccine development had to be done in parallel whereby normally you go in series – first you have a disease, you understand the disease with some of the basic science and the epidemiology of the illness. You start testing different vaccine candidates for what might protect and what might provide protection, and you can build a sense of history and understanding to enable you to finally pick a vaccine to take forward into human clinical trials.
For instance, the Ebola virus had a 30-year history before the recent epidemic, although research was limited by funding constraints. It was only because of the West African epidemic in 2014 that provided the impetus to bring vaccines forward that had been in developments for 10-15 years. With Zika, prior to October/November 2015, when the first microcephaly cases were reported, there was no reason to think that Zika was anything more than a nuisance illness and we needed to get involved. We started our vaccine program in early November and so all of the basic science research and the planning for the clinical trial were ongoing simultaneously.
CTA: What data were you able to collect that were enough to justify you gaining approval to run a vaccine trial?
JM: There were three parts that allowed us to move forward. One was a basic understanding of whether this was a safe platform for a vaccine.DNA vaccines have been in development since circa 1998 – 20 years now. The safety of the platform has been well established. The way DNA vaccines work is that the vaccine is injected into tissue and the body makes proteins from the DNA to then generate an immune response. The DNA only lasts in the body for a few weeks. That helped us move forward considering there were no inherent safety concerns. The bigger question is what information did we need to allow the vaccine program to move forward? We had to make the decision to start to take a vaccine candidate through the manufacturing process, with the concomitant/financial commitments that were required of us – while we were completing the basic science to determine that we were assured that this vaccine was the one to bring forward into clinical trials.
We determined that the vaccine candidate worked well in cells, and then showed that mice and other animals including monkeys generated strong immune responses that would be consistent with protection from Zika infection. Finally, we were able to prove that vaccination of immune deficient mice were fully protected from Zika virus infection, even after a single dose of our vaccine candidate, whereas unvaccinated mice die after being infected with Zika. Importantly, immune serum from vaccinated monkeys was also able to protect immune deficient mice from infection. So we knew before we went to government agencies, that we had demonstrated immune responses and had shown protection in mice and thought that the vaccine candidate would be a strong contender to also protect humans from infection. Thus, the filing package was as or more complete than any other prior vaccine candidate as far as safety and effectiveness in animals – despite having such a short time to gather and complete all of the necessary parts.
When we decided to go forward in production, there was a large financial commitment before we had all necessary data knowing that if the vaccine candidate did not work, it could all be for naught.
CTA: Are the initial signs encouraging?
JM: As far as progress is concerned, the responses will be determined at our primary endpoint which is our week 14 reading. Our vaccine trial is a three-vaccination series. The first is given at study entry, the second four weeks later, and then at 12 weeks from the start of each person that enters the study. The first read out will be given two weeks after the final vaccination. The study enrolled quickly and is progressing well.
CTA: In instances where you have an epidemic, how difficult is it to develop a vaccine quickly and efficiently?
JM: Although there are many similarities between Zika and Ebola in terms of developing a vaccine, there are noticeable differences. One similarity is that you need to have a proper readout that demonstrates whether or not the vaccine is working. With a disease like Ebola, a significant challenge was the ethics of having a control group – a group that doesn’t get the vaccine but is part of the trial. If you truly believe the vaccine will work then you need to have protections in place to enable the trial to be terminated if there’s a sign that the vaccine is working.
With Zika, the group we’re attempting to immunise are women who can potentially become pregnant. Zika has only rarely caused fatal disease. This means we can go forward with a control group. The real concern with Zika is that the epidemic is changing in real time, almost as though you’re trying to jump on to a moving train where you can’t even see the train. As Zika goes through one region, that region might already have had enough infections that there aren’t enough people to get infected. If an epidemic moves quickly, by the time you decide to go into a country and get everything set up to conduct a trial, the epidemic might have already passed. When we decided to start our second trial in Puerto Rico, that planning started early in the year to say where do we think the epidemic will be so we may have chance to see if the vaccine might work.
CTA: Is the industry winning the battle against Zika?
JM: The response to Zika has been exceptionally strong. There have been many companies that have looked to develop diagnostics and therapeutics. I think that the lessons from Ebola were very fresh in everybody’s mind.
Zika will require a very large international effort. The ability to protect people will likely rely on an effective vaccine but certainly one of the most important ways to combat the virus, even with an effective vaccine, is by local mosquito control.
*Joel Maslow is the Chief Medical Officer of GeneOne Life Science
PHOTO CREDIT: Animal Diversity Web via Flickr