Fewer side effects helped spur Pfizer, BioNTech to advance BNT162b2 over earlier COVID-19 vaccine candidate

Pfizer and BioNTech released more details about why they recently selected their experimental coronavirus vaccine BNT162b2 over another candidate to advance into late-stage testing. According to a paper available on the medRxiv preprint server presenting additional Phase I data from an ongoing US trial of their BNT162 mRNA-based vaccine programme, both BNT162b2 and the previous leading candidate, BNT162b1, induced similar immune responses in both younger and older adults, but BNT162b2 was found to be "associated with less systemic reactogenicity, particularly in older adults."

The companies previously indicated that BNT162b2 was chosen over BNT162b1 "based on the totality of available data" from preclinical and clinical testing, "including select immune response and tolerability parameters."

The trial recruited healthy adults from 18 to 55 years, as well as an older cohort of people between 65 and 85, who were randomised to receive two doses at 21-day intervals of placebo, or either of the two nucleoside-modified RNA vaccine candidates. BNT162b1 encodes a secreted trimerised SARS-CoV-2 receptor-binding domain (RBD), while BNT162b2 encodes a prefusion stabilised membrane-anchored SARS-CoV-2 full-length spike. Positive interim findings of BNT162b1 in younger adults were previously reported from the US study, as well as from a German cohort.

Milder systemic events

In the new data, younger adults given BNT162b1 reported mild-to-moderate local reactions, primarily pain at the injection site, within seven days after an injection, which was more frequent after the second dose. Among older adults, BNT162b1 elicited "similar, but milder" local reactions, with mild-to-moderate injection site pain reported by 92% after the first dose and 75% after the second. "A similar pattern was observed after vaccination with BNT162b2," the companies said, adding that "no older adult who received BNT162b2 reported redness or swelling [and] no participant who received either BNT162 vaccine reported a Grade 4 local reaction."

Meanwhile, systemic events after administration of BNT162b2 were milder than those with BNT162b1. Specifically, after the second dose of BNT162b1 at 30 mcg, 75% of the younger and 33% of the older participants reported fever ranging from 38.0 to 38.9 °C, whereas among those given 30 mcg of BNT162b2, the rates were 17% and 8%, respectively. Further, severe systemic events such as fatigue, headache, chills, muscle pain, and joint pain were reported in "small numbers" of younger BNT162b2 recipients and were "transient and manageable," while no severe systemic events were reported by older BNT162b2 recipients. There were also no reports of Grade 4 systemic events by any BNT162 recipient.

Neutralising GMTs

In terms of efficacy, both vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralising antibody geometric mean titers (GMTs) in the younger and older adults. Pfizer and BioNTech said that seven days after the second dose, BNT162b2 at 30 mcg induced neutralising GMTs among the younger adults that were 3.8 times the GMT of a panel of 38 sera of convalescent patients. In older adults, it was 1.6 times the GMT of the same panel.

The companies previously said that compared to the BNT162b1 candidate, BNT162b2-vaccinated participants also displayed a "favourable breadth of epitopes recognised in T-cell responses." They said BNT162b2 also triggered high magnitude CD4+ and CD8+ T-cell responses against the virus' RBD, as well as against the remainder of the spike glycoprotein that is not contained in BNT162b1.

'On track' for October filing

"It is important to us to continue sharing data and related information on our COVID-19 vaccine lead candidate," commented BioNTech CEO Ugur Sahin, adding that "the favourable safety profile of BNT162b2 and the breadth of T-cell responses we previously announced have supported our decision to select this candidate for the pivotal Phase II/III study." He noted that the companies have already dosed more than 11,000 participants with BNT162b2 in that study, which aims to enrol up to 30,000 people between 18 and 85 years of age.

Pfizer and BioNTech also noted they are on track to seek regulatory review for BNT162b2 as early as October and reiterated that their aim is to supply up to 100 million doses globally by the end of 2020, and approximately 1.3 billion doses by the end of next year.

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