Pfizer, BioNTech Choose Full Spike Protein for Pivotal Vaccine Test

Xconomy New York — 

Pfizer and BioNTech’s COVID-19 vaccine research started with multiple approaches—four shots on the messenger RNA goal. The partners have narrowed their choices to one for pivotal testing, and that candidate takes the same tack as other companies trying to address the novel coronavirus.

BNT162b2, the vaccine candidate that Pfizer (NYSE: PFE) and BioNTech (NASDAQ: BNTX) will advance to a Phase 2/3 study, is designed to get cells to produce the full spike protein of the novel coronavirus as a way to spark immunity. The choice is somewhat of a surprise. Earlier this month, the companies published preliminary Phase 1 data for BNT16b1, a candidate that codes for one piece of the spike protein called the receptor binding domain.

In preclinical and clinical testing so far, both candidates showed encouraging immune responses, including the production of neutralizing antibodies that can stop the novel coronavirus. But patient comfort appears to be a deciding factor. The companies said that the candidate that codes for the full spike protein was better tolerated by patients, with the resulting systemic events—fever, chills, and fatigue—considered mild to moderate in acuity and clearing up within two days. That candidate also did not produce any serious adverse events, the companies said.

Another factor is BNT162b2’s potential to better protect older adults, who are more vulnerable to the novel coronavirus. In adults age 65 to 85, the candidate that codes for the full spike protein displayed more epitopes, parts of an antigen that stimulate an immune response. This could be important for producing an immune response that is not only robust, but also longer lasting. Some studies of patients who have recovered from COVID-19, as well as clinical tests of experimental vaccines, suggest that antibodies to the novel coronavirus decline over time.

The emphasis on T cell activity shows the importance that companies are placing on this immune response in addition to the production of neutralizing antibodies, SVB Leerink analysts wrote in a research note. They add that China-based CanSino Biologics, which is in late-stage testing with its vaccine candidate, has reported data showing that T cell responses to its vaccine candidate did not decline with age.

The CanSino vaccine isn’t an mRNA vaccine, like the ones in development from Moderna (NASDAQ: MRNA) and Pfizer and BioNTech. It’s made from an adenovirus engineered to express the novel coronavirus’s spike protein. Oxford University and AstraZeneca (NYSE: AZN) are taking a similar approach with their experimental COVID-19 vaccine.

Pfizer and BioNTech’s vaccine candidate selection means that all of the leading COVID-19 vaccine companies are targeting the spike protein, according to the SVB Leerink note. The analysts are awaiting Phase 2 and 3 efficacy data to compare the mRNA candidates. Early data so far suggest that the Pfizer/BioNTech vaccine candidate elicits stronger T cell responses than Moderna’s candidate, the analysts wrote. If that stronger response holds up, and if that response proves to be critical for conferring immunity across a broader population, the Pfizer and BioNTech candidate could have an edge.

The BNT162b2 Phase 2/3 study is expected to enroll up to 30,000 volunteers, ages 18 to 85, at 120 clinical trial sites around the world. Participants will be randomly assigned to receive either the vaccine candidate or a placebo. The main goals are prevention of COVID-19 in those who have not been previously infected by the novel coronavirus, and prevention of the disease regardless of whether or not a person has been previously infected. Secondary goals include prevention of severe infection in those groups.

If the study is successful, the companies say an application seeking emergency authorization or other form of regulatory approval could be filed as early as October. If given the green light, they say that they can produce up to 100 million doses by the end of the year, ramping up to 1.3 billion doses by the end of 2021.

Pfizer and BioNTech aren’t completely shelving the other three COVID-19 vaccine candidates from their research collaboration. They are continuing to collect Phase 1/2 data on all four candidates, which they say will be submitted for peer review and potential publication “in the near future.”

Image: iStock/rimglow 

 

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