SARS-CoV-2 Vaccine Shows Signs of Activity in Phase 1/2 Study

BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA vaccine candidate expressing the SARS-CoV-2 receptor binding domain (RBD), elicited promising early signs of immune activity in a placebo-controlled phase 1/2 study, according to early data reported by Pfizer and BioNTech, the companies co-developing the vaccine.

Various doses of the vaccine were assessed in the phase 1/2 study, with the highest level of subsequent IgG and neutralizing antibodies seen in subjects receiving BNT162b1 as an initial immunization followed by a booster. Subjects receiving this schedule of the vaccine (n = 24) had 8.0 to 46.3 times higher geometric mean concentrations (GMCs) of SARS-CoV-2 RBD-binding IgG antibodies compared with sera from patients who had recovered from SARS-CoV-2. Moreover, geometric mean titers (GMTs) were 1.8 to 2.8 times higher for SARS-CoV-2 neutralizing antibodies in vaccinated subjects compared with sera from convalescent patients.

“These preliminary data are encouraging in that they provide an initial signal that BNT162b1, targeting the RBD SARS-CoV-2, is able to produce neutralizing antibody responses in humans at or above the levels observed in convalescent sera—and that it does so at relatively low dose levels," Ugur Sahin, MD, CEO and co-founder of BioNTech, said in a statement. "We look forward to providing further data updates on BNT162b1.”

The preliminary results were published in a medRxiv preprint, and included data for 45 patients: 24 received two injections of BNT162b1 21 days apart (10 µg or 30 µg as a starting dose following by a switch to the alternative dose) and 12 received a single 100 µg injection of the vaccine. There were 9 subjects who received a matched placebo (3 matched for each starting dose). The mean age of participants was 35.4 years (range, 19-54), 51.1% were male, and most participants were white (82.2%). SARS-CoV-2 RBD-binding IgG concentrations were assessed at baseline, day 7, day 28, and day 35 following immunization. A panel of 38 sera samples from patients who had recovered from SARS-CoV-2 were also assessed as part of the analysis.

Across all vaccination dose levels at day 21, IgG GMC levels in the subjects ranged from 534 to 1778 units/ml. In convalescent sera panels, IgG GMC at ≥14 days after confirmed SARS-CoV-2 PCR diagnosis was 602 units per mL, suggesting comparable levels between groups. In subjects receiving a booster of the vaccine, there was a significant increase in IgG GMC levels 7 days following the day-21 dose (day 28). In these groups, IgG GMCs ranged from 4813 to 27,872 units/ml. An increase from day 21 to day 28 was not observed in the single-dose arm. By day 35, IgG GMCs remained elevated in the vaccinated group at 5880 to 16,166 units per ml.

Increases in SARS-CoV-2 neutralizing antibodies were observed across all doses, with the highest increase seen in the dual dose arm. In this group, 50% SARS-CoV-2 neutralizing GMTs reached 168 to 267 compared with 94 in the convalescent plasma group. Data for this end point continue to be evaluated. Findings for IgM were not yet reported.

The most frequent adverse events (AEs) were pain at the injection site, which was reported after the first dose for 58.3% of patients receiving 10 µg, for 100% of those receiving an initial 30 µg or 100 µg dose, and for 22.2% of those in the placebo arm. For those receiving a second dose, injection site pain was reported for 83.3% of those receiving the smaller dose and for 100% of subjects receiving the larger dose. This occurred for 16.7% of participants in the placebo group. Pain was rated as mild or moderate, except for 1 instance of severe pain in the 100-µg arm.

Other common systemic AEs included fatigue, headache, chills, muscle pain, and fever. AEs were more common in the 100-µg dose arm (58.3% of participants) compared with the dual dose arm (50%) and the placebo group (11.1%). There were two severe AEs reported, including grade 3 pyrexia 2 days after vaccination in the 30-µg group and a sleep disturbance in the 100-µg group. In the dual dose group, 8.3% of patients experienced fever (≥38.0 °C) following a second dose of 10 µg compared with 75% of those receiving BNT162b1 at 30 µg.

“We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings,” Kathrin U. Jansen, PhD, senior vice president and Head of Vaccine Research & Development, Pfizer, said in a statement. “We are dedicated to develop potentially groundbreaking vaccines and medicines, and in the face of this global health crisis, we approach this goal with the utmost urgency. We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible.”

Pfizer, which is assessing a number of potential vaccines for SARS-CoV-2, expressed plans to begin a phase 2b/3 study later this month for the most promising candidate. The company indicated the ability, should approval be granted, to manufacture more than a million doses of a vaccine candidate by the end of 2020 and more than 1.2 billion doses by the end of 2021.