[Updated 7/2/2020, 9:27 a.m. See below.] A BioNTech messenger RNA vaccine candidate for COVID-19 has shown in a small study that it can elicit an immune response to the novel coronavirus.
The 45-patient US study tested three doses of the experimental mRNA vaccine, BNT162b1, along with a placebo. Early results now available show higher levels of the antibodies hoped to neutralize the virus compared to what has been observed in patients who recovered from COVID-19. No serious safety problems were reported in the Phase 1/2 clinical trial results announced Wednesday, which were also published in a preprint, a research paper that has not yet been peer reviewed.
Speaking on a conference call to discuss the data, BioNTech (NASDAQ: BNTX) CEO Ugur Sahin described the early findings as “positive,” but also listed several caveats. The level of T cell response elicited by the vaccine is not yet available. Those responses were measured in a separate German clinical trial, the results of which will be published next week, Sahin said. He added that even though the vaccine candidate generated high levels, or titers, of antibodies, it’s still unknown if those levels are enough to offer protection. Another open question is the durability and safety of the vaccine. Sahin noted that the early results don’t go beyond two weeks after patients received the second dose.
“This is of course important for public health use of the vaccine,” he said. “A vaccine should have high titers over longer periods of time.”
BioNTech plans to gather additional data in the coming months to learn more about the immune response and safety of the vaccine. But in the nearer term, the initial results will be used to choose which vaccine and dose to test in a Phase 2b/3 clinical trial, which the company anticipates will start by July’s end, Sahin said.
The vaccines in development by BioNTech are based on an experimental technology that gets mRNA, snippets of genetic information with instructions for producing proteins, into cells. The idea is to coax the cell into making a protein from the virus. That protein by itself doesn’t cause infection but it’s hoped to be enough to spark a response that confers immunity.
Other companies are also working on potential mRNA vaccines to tackle the pandemic’s spread. Cambridge, MA-based Moderna (NASDAQ: MRNA) is furthest along, gearing up for a Phase 3 test of an mRNA vaccine that codes for the spike protein on the outer shell of the novel coronavirus. Sanofi (NYSE: SNY) and Translate Bio (NASDAQ: TBIO) have struck up a COVID-19 vaccine alliance to develop mRNA vaccines, but haven’t yet advanced a candidate into human testing.
The spike protein being targeted by Moderna and others is also the focus of BioNTech, but the company is pursuing four different approaches in its effort to neutralize the virus. The results released Wednesday are for a vaccine that carries the genetic instructions for the receptor binding domain, a spot on the tip of the spike protein. It’s one of two vaccines that BioNTech is developing for that target. The other two vaccine candidates carry the genetic instructions for the entire spike protein. All of the candidates are part of “Project Lightspeed,” the German company’s coronavirus vaccine partnership with Pfizer (NYSE: PFE).
The volunteers in the BioNTech study received two doses, 21 days apart, of either 10 micrograms or 30 micrograms of BNT162b1, or a placebo. Another group was given a single 100-microgram dose of the BioNTech vaccine.
According to the results released Wednesday, after 28 days—one week after the second dose—all patients who received the low or middle dose had elevated levels of the antibody for the receptor-binding domain. In the lowest dose group, comprised of 12 patients, that level was eight times higher than what was observed in those who had recovered from COVID-19. In the middle dose group, also comprised of 12 patients, the levels of antibodies to receptor-binding domain were 46.3 times higher. No second injection was given to the 12 patients in the highest dose group after a higher number of patients experienced reactions to the vaccine without showing a significant increase in an immune response compared to the mid-dose group, BioNTech said.
In the low dose group, the average level of neutralizing antibodies—the type that can stop the virus—was 1.8 times higher compared to levels in patients who have recovered from COVID-19. In the middle dose group, neutralizing antibody levels were 2.8 times higher.
The vaccine was well tolerated by patients, with pain at the injection site being the most common reaction. In the group given the highest dose, one patient reported severe pain, Sahin said. Systemic problems, such as fever, fatigue, and chills were more common after the second dose. Most of those problems peaked the day after receiving the injection and resolved within a week.
The patients enrolled in the study were between the ages of 18 and 55. Sahin cautioned that it’s not yet known what kind of immune response the vaccine will elicit in older people, who are at higher risk for severe illness from COVID-19. Later-stage tests will have a more diverse enrollment, and, in addition to evaluating the vaccine in older people, include those with chronic and underlying health conditions, who are also more at risk, he said.
[The following two paragraphs added with analyst comments.] In a Thursday research note, SVB Leerink analysts wrote that the promising antibody and immune response data for the BioNTech vaccine were expected. The next steps bring greater challenges as the companies must translate those responses into meaningful clinical efficacy in a larger group of patients. As Project Lightspeed progresses to a larger study, the focus shifts to the capabilities of Pfizer. The pharmaceutical giant expects that a pivotal clinical trial starting later this month could be fully enrolled in August, then produce early efficacy data in September.
SVB Leerink anaylsts said the ambition of Pfizer’s timeline is laudable, but challenging. Recruiting 30,000 patients in four weeks is unprecedented; the fastest enrollment that the firm could find was a GlaxoSmithKline (NYSE: GSK) flu vaccine confirmatory study in 2005 that enrolled 6,213 patients in one month. “Maintaining high quality in a global trial of this scale and speed is incredibly difficult and, for us, remains a risk for the program,” the research note said.