Pfizer (PFE) and BioNTech (BNTX) announced positive data evaluating the safety, tolerability, and immunogenicity of two omicron-adapted COVID-19 vaccine candidates: one monovalent and the other bivalent, a combination of the Pfizer-BioNTech COVID-19 vaccine and a vaccine candidate targeting the spike protein of the Omicron BA.1 variant of concern. Data from the Phase 2/3 trial found that a booster dose of both omicron-adapted vaccine candidates elicited a substantially higher immune response against Omicron BA.1 as compared to the companies' current COVID-19 vaccine. The robust immune response was seen across two investigational dose levels, 30 microgram and 60 microgram. The Omicron adapted vaccine candidates studied in the Phase 2/3 trial in 1,234 participants 56 years of age and older elicited substantially higher neutralizing antibody responses against Omicron BA.1 when compared to the companies' current COVID-19 vaccine. The pre-specified criterion for superiority was measured by the ratio of neutralizing geometric mean titers with the lower bound of the 95% confidence interval greater than 1. The geometric mean ratios for the monovalent 30 microgram and 60 microgram vaccines compared to the current COVID-19 vaccine were 2.23 and 3.15, respectively. The GMRs for the bivalent 30 microgram and 60 microgram vaccines compared to the current COVID-19 vaccine were 1.56 and 1.97, respectively. The monovalent Omicron-adapted vaccine 30 microgram and 60 microgram achieved a lower bound 95% confidence interval for GMR of greater than1.5, consistent with the regulatory requirement of super superiority. Demonstration of superiority against omicron and safety are regulatory requirements for potential emergency use authorization of a variant-adapted vaccine. One month after administration, a booster dose of the omicron-adapted monovalent candidates increased neutralizing geometric mean titers against Omicron BA.1 13.5 and 19.6-fold above pre-booster dose levels, while a booster dose of the Omicron-adapted bivalent candidates conferred a 9.1 and 10.9-fold increase in neutralizing GMTs against Omicron BA.1. Both omicron-adapted vaccine candidates were well-tolerated in participants who received one or the other omicron-adapted vaccine. In a SARS-CoV-2 live virus neutralization assay tested on sera from participants over 56 years of age and older, sera efficiently neutralized BA.4/BA.5 with titers approximately 3-fold lower than BA.1. Pfizer and BioNTech will continue to collect additional study data on Omicron BA.4/BA.5 over the coming weeks.

Ionis Pharmaceuticals announced that GSK (GSK) presented results from an interim analysis of the Phase 2b B-Clear clinical study of bepirovirsen - formerly IONIS-HBVRx, an investigational antisense medicine for the treatment of patients with chronic hepatitis B virus. The data were presented in an oral late-breaker session at the European Association for the Study of the Liver's International Liver Congress 2022 in London, U.K. The final results from the study will be submitted for presentation at a scientific congress later this year, and for publication in a peer-reviewed journal. In the study, 28% of patients on standard of care, which is stable nucleoside/nucleotide analogue, and 29% of patients not on NA treatment, experienced a virologic response on 300 mg of bepirovirsen weekly, following 24 weeks of treatment. Virologic response is defined as serum/plasma levels of hepatitis B virus DNA and hepatitis B surface antigens below the lower limit of quantification. Up to 68% of patients on NA therapy and up to 65% of patients not on NA achieved HBsAg less than100 IU/mL at the end of treatment. End-of-treatment virologic responses were observed in patients with high or low baseline HBsAg levels, who were hepatitis B e-antigen negative or positive, and who were receiving NA treatment or not, indicating that bepirovirsen has the potential to treat broad segments of the CHB population. Durability of the responses is being assessed. Treatment-related serious adverse events were observed in less than 1% of patients receiving NA treatment and 1% of patients who were not on NA. SAEs were reported in 3% and 4% of patients receiving NA treatment and those who were not on NA, respectively. There were no clinically meaningful differences in adverse events across treatment arms in either trial. GSK is also exploring combinations of bepirovirsen and other therapeutic modalities in the following trials. Combination treatments could increase functional cure rates in more patients, thereby further reducing the global disease burden of CHB. Trials include: