WASHINGTON. Prefusion F-protein vaccine candidates for respiratory syncytial virus (RSV) were shown to be safe in adults aged 60 years and older and demonstrated the ability to thwart lower respiratory tract disease, including severe cases, a pair of researchers showed. large phase III trials.
A single dose of an RSV prefusion protein F vaccine (RSVPreF3 OA) produced a vaccine efficacy of 82.6% against lower respiratory tract disease (96.95% CI: 57.9-94, 1), which met the study’s primary endpoint, with vaccine efficacy reaching 94.1% against severe disease. RSV disease (95% CI: 62.4-99.9), reported Michael Ison, MD, MS, of Northwestern University Feinberg School of Medicine in Chicago, in the annual WeekID meeting.
In the second trial, a single dose of another RSV prefusion protein F vaccine (RSVPreF) showed 66.7% efficacy against two or more lower respiratory tract symptoms of RSV (96.66% CI: 28, 8-85.8) and 85.7% against three or more symptoms (96.66% CI: 32.0-98.7), meeting the study’s co-primary endpoints, according to Edward Walsh, MD, of the University of Rochester in New York.
Currently, there are no vaccines to protect against RSV infection. According to data from the Centers for Disease Control and Preventionapproximately 177,000 older adults in the US were hospitalized due to RSV infections in 2017 alone, and 14,000 died.
“For someone who has been working in the field for a long time, I couldn’t be more excited about the advances we’re seeing, particularly with respiratory syncytial virus vaccines,” said session moderator Kathleen Neuzil, MD, of the University of Maryland in Baltimore, presenting the anticipated judgments.
Phase III AReSVi-006 (Respiratory syncytial virus in adults) The RSVPreF3 OA trial presented by Ison included 24,960 adults aged 60 years and older (mean 69.5 years) who were randomized 1:1 to vaccine or placebo. The case definition for the study was the presence of lower respiratory symptoms or signs for at least 24 hours along with RSV detected by RT-PCR. By this definition, seven people who received the vaccine developed lower respiratory tract illness due to RSV versus 40 among those who received placebo.
Severe cases involved at least two lower respiratory signs or were assessed as severe by the investigator and confirmed by the external adjudication committee, or were based on the use of supportive therapy. One case of severe lower respiratory tract illness occurred in the vaccine group and 17 in the placebo group.
The treatment and placebo groups were similarly matched by age: 56% were 60 to 69 years old, 36% were 70 to 79 years old, and 8% were 80 years or older. Most of the participants were white (about 79%), while 9% were black and 7.6% were Asian.
For the primary endpoint, the vaccine performed similarly across RSV subgroups and age groups:
- RSV A: 84.6%
- RSV B: 80.9%
- Age 60-69 years: 81.0%
- Age 70-79 years: 93.8%
In people 80 and older, and in frail people, too few cases have occurred to assess effectiveness, according to Ison. Efficacy against lower respiratory tract disease appeared consistent regardless of comorbidity status (72.5% for none and 94.6% for one or more) and was 92.9% for those considered pre-frail and 80% for those considered pre-frail. % for which they were considered suitable.
Baseline comorbidities were reported in just under 40% of participants and included chronic obstructive pulmonary disease (COPD), asthma, any chronic lung/respiratory disease, chronic heart failure, diabetes, and advanced liver or kidney disease.
The safety profile was good, Ison said. Adverse events (AEs) included arm pain, fatigue, headache and myalgia that “generally resolved very quickly,” she added. No imbalances were observed for serious AEs.
Phase III RENOIR The trial included 34,284 participants aged 60 years or older (mean age 68.3 years). Walsh presented an interim analysis of the trial with approximately 6 months follow-up.
For the two-symptom endpoint, 11 cases of lower respiratory tract illness occurred in the treatment group versus 33 in the placebo group, with symptoms including cough, wheezing, sputum production, shortness of breath, pain throat, nasal congestion and runny nose. For the three-symptom endpoint, two cases occurred in the vaccine arm versus 14 among controls.
All participants were in good health or had stable chronic medical conditions, Edwards said, and people with immunocompromised conditions were excluded.
Participants had a mean age of 68 years, approximately 78% were white, 37% Hispanic, 8% black, and 8% Asian. The age groups were again well matched: 63% were 60-69 years old, 32% were 70-79 years old, and 6% were 80 years old or older.
High-risk conditions included chronic cardiopulmonary conditions in 15-16%, asthma in 9%, COPD in 6%, and congestive heart failure in 2%. Additionally, 19% had diabetes and 13% had heart disease.
Local reactions, such as injection site pain, redness and swelling, were observed in 12.1% of the treatment group versus 6.6% of the placebo group. Overall AEs were seen in 27.4% vs. 25.7%, respectively; these included local pain at the vaccination site, fatigue, headache, muscle pain, joint pain, diarrhoea, fever, nausea and vomiting.
In his presentation, Edwards confirmed the difficulty that COVID created for the trial, which began in August 2021 at his center.
“This was the worst possible time to do an efficacy trial for a non-COVID disease,” he said. “Within our center we had more COVID than other types of respiratory infections.”
Both trials will report 1-year follow-up data when available.
The RENOIR study was funded by Pfizer, while AReSVi-006 was funded by GSK.
Walsh reported relationships with Merck and Pfizer. Multiple co-investigators are employees or shareholders of Pfizer.
Ison disclosed relationships with GSK, Adagio Therapeutics, Adamis Pharmaceuticals, ADMA Biologics, AlloVir, Atea Pharmaceuticals, Cidara Therapeutics, CSL Behring, Genentech/Roche, Janssen, Merck, Pulmocide, Shionogi, Seqirus, Takeda, Talaris Therapeutics, and Viracor Eurofins. Several co-investigators are employees or shareholders of GSK.