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0610 Novavax QA
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Novavax U.S. Phase III results unblinded next week, EUA submission in 3Q

Jun 11, 2021 | 12:30 AM GMT

Novavax expects to disclose results from the U.S. Phase III trial of its COVID-19 vaccine next week, Stanley Erck, its president and CEO, said Thursday at an event marking the start of construction of the company’s new campus in Gaithersburg, Maryland.

The company plans to submit an emergency use authorization (EUA) application to FDA in the third quarter, President of R&D Gregory Glenn told BioCentury. Novavax Inc. (NASDAQ:NVAX) had hoped to submit an EUA earlier this year based on data from a U.K. Phase III study and a Phase II study conducted in South Africa, but FDA pushed for the U.S data.

The U.S. trial results will include sequencing data that will provide insights into the vaccine candidate’s ability to protect against SARS-CoV-2 variants. The trial of the Novavax vaccine candidate, a protein-based product adjuvanted with the company’s proprietary saponin-based Matrix-M, is likely to be the last large, placebo-controlled COVID-19 vaccine trial conducted in the U.S., Glenn said.

In a conversation with BioCentury Thursday, Glenn discussed the trial, expectations that immunity will wane over time, and the need for boosters and possibly vaccines optimized to protect against specific variants. Novavax is one of seven COVID-19 vaccine manufacturers participating in a U.K. mix-and-match study of boosters. 

The conversation, edited for clarity, follows.

BioCentury: What's the timing for completion of your Phase III trial and submission of an EUA in the United States?

Gregory Glenn: Very shortly we'll unblind our last pivotal trial, the U.S. trial, and that data will be part of our EUA package. That was an incredible effort. The start of the trial was late December. That was in the context of some vaccines beginning to get EUAs and especially some of the target high-risk populations [getting vaccinated]. It is really amazing that we got the trial done. I'm quite certain we're going to have a robust result and we'll know that shortly.

BioCentury: Do you have data on efficacy in protecting against different variants that were circulating during the trial?

Glenn: Yes, we will have [that]. The trial was a collaboration with the NIH and NIAID. They had a big contribution, one of which was to do the sequencing of the virus at the University of Washington. Not every sample had enough virus to be actually sequenced, which is much more rigorous than actually detecting whether it's COVID or not, but most of the viruses we will have sequences on. That will be very interesting, to see what's going on in a controlled way in the U.S. with viruses.

We expect that there's a lot of migration to the B.1.1.7, the U.K. virus, which is highly transmissible. We expect a lot of those, but also other variants because this virus really mutates. It is going to be important evidence as to whether our vaccine could protect against the variations that we see in the field.

BioCentury: Are you concerned that when efficacy of your vaccine is reported it's not going to be apples-to-apples in comparison to the mRNA vaccines that were tested at a time when there weren't many variants circulating?

Glenn: That’s a good point. We are able to [determine] if some of the viruses are similar to the prototype, if you will. We actually have called that out as a key analysis, so we will be able to get an idea of the apples-to-apples situation and the variants.

BioCentury: You will unblind the U.S. Phase III trial soon. Do you expect the same kind of speed on the EUA process as happened with the previous vaccines?

Glenn: What we've been guiding for is a quarter three submission. Not having had a manufacturing facility, we had to build the company and the infrastructure, so we won't see a scenario like [those for vaccines from established manufacturers], but the package is very mature.

We're talking to a number of regulators, from the U.S., the U.K., EMA as well as India.

BioCentury: At this point in the U.S. and Europe any new vaccine is most likely to be used as a booster. What’s the regulatory pathway for a booster?

Glenn: It's not something FDA or anybody has really outlined, but everybody knows boosting is going to be important.

Typically, what you do is do a trial addressing a subject of interest, provide robust safety and immunogenicity data in this case to regulators and say, here's the support for the use of this as a booster. I think that's going to be quite critical.

In the U.S. it's likely that most people will have had some experience with the vaccine, but we know immunity to vaccines is going to wane, especially in populations that were originally naive. My prediction is that in six to 12 months we’ll see immunity going back to baseline. We don't want the virus to come back in a big way, so boosting is going to play a major role.

We're trying to position ourselves with data from very well-conducted studies where we're doing mix-and-match with different regimens already given. We are boosting, for example, our subjects who were in the Phase II trial. They've been boosted at six months. We'll have both the immune response at six months, and from the boost, which we expect to be dramatic, and we're doing that at 12 months as well.

Those create data packages that can support safety. In this case, it will likely be just immunogenicity data. We've come to understand that immune responses are protective.

BioCentury: So you think you'll be able to get authorization or approval for a booster based on immunogenicity data?

Glenn: I think the days of doing randomized placebo-controlled trials [of COVID-19 vaccines] are over. At least in the U.S. we're closing the chapter on that. If there are available vaccines, it's not really ethical to conduct placebo-controlled trials.

In our trial, because this is such a transition, we offered a crossover where people knew that at the end of the trial they were going to get an active vaccine. They always had the ability to elect to get an EUA vaccine. In the first month or so of the trial we had a lot of dropouts of people who wanted to be sure that they got a vaccine and since our safety profile is so good they didn't have an idea of whether they received a placebo or a vaccine.

BioCentury: What's your strategy on variants? Will there be an overlap period when the original version of the vaccine is marketed along with one aimed at variants?

Glenn: It is possible because our vaccine presents conserved epitopes — and we're going to see from the data in the U.S. and we already have seen some data in the U.K. — that we cover variants quite well.

The other piece of that though, is what happens in six or 12 months when immunity is waning. That's when the rubber is going to hit the road. Based on the data we have, it could be that boosting is sufficient because our vaccine is very immunogenic.

We are also making [vaccine candidates for] all the known variants and even for a few Frankensteins, things that are mixed and matched with some of the major mutations.

We intend to test the B.1.351, which is a South African variant, in a clinical trial. The important feature of that vaccine would be does the immune response coverage include the prototype strains [as well as] other variants of that are of interest.

I think, going back to the U.S. trial, that we're going to have a very interesting situation because we'll get to answer the question of how our vaccine works against variants of interest or of concern.

We want to be ready if there is a call for variant vaccination. We will have a good candidate and it would be built on the safety, efficacy, immunogenicity and CMC package submitted to regulators.

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