WASHINGTON – Prefusion’s F-protein respiratory syncytial virus (RSV) vaccine candidates have been shown to be safe in adults 60 and older while demonstrating an ability to thwart lower respiratory tract disease, including severe cases , showed two large phase III trials.
A single dose of an RSV prefusion protein F vaccine (RSVPreF3 OA) resulted in 82.6% vaccine efficacy against lower respiratory tract disease (96.95% CI 57.9-94.1 ), meeting the primary endpoint of the study, and vaccine efficacy landed at 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, at the annual IDWeek meeting.
In the second trial, a single dose of another RSV prefusion F-protein vaccine (RSVPreF) showed 66.7% efficacy against at least two lower respiratory tract RSV symptoms (96 ,66%: 28.8-85.8) and 85.7% against three or more symptoms (96.66% CI 32.0-98.7), meeting the co-primary endpoints of study, according to Edward Walsh, MD, of the University of Rochester in New York.
Currently, no vaccine exists to protect against RSV infection. According to CDC data, approximately 177,000 elderly people in the United States were hospitalized due to RSV infections in 2017 alone, and 14,000 died.
“For someone who has been in the field for a very long time, I couldn’t be more excited about the progress we’re seeing, especially with respiratory syncytial virus vaccines,” said session moderator Kathleen Neuzil. , MD, of the University of Maryland in Baltimore, presenting the scheduled trials.
The phase III AReSVi-006 (adult respiratory syncytial virus) trial in osteoarthritis RSVPreF3 presented by Ison included 24,960 adults aged 60 years and older (mean 69.5 years) who were randomized 1 :1 to receive the vaccine or the placebo. The case definition for the study was the presence of lower respiratory symptoms or signs for at least 24 hours with RSV detected by RT-PCR. By this definition, seven people who received the vaccine developed lower respiratory tract disease from RSV compared to 40 in people who received the placebo.
Severe cases involved at least two lower respiratory signs or were assessed as severe by the investigator and confirmed by the external screening committee, or were based on the use of supportive therapy. One case of severe lower respiratory disease occurred in the vaccinated group and 17 in the placebo group.
The treatment and placebo groups were similarly matched for age: 56% were 60-69 years old, 36% were 70-79 years old, and 8% were 80 years or older. Most participants were white (about 79%), while 9% were black and 7.6% were Asian.
For the primary endpoint, the vaccine showed similar results in all RSV subgroups and age groups:
- RSV A: 84.6%
- RSV B: 80.9%
- Age 60-69: 81.0%
- Age 70-79: 93.8%
In people 80 and older and 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 judged to be prefrail and 80% for those deemed suitable.
Baseline comorbidities were reported in just under 40% of participants and included chronic obstructive pulmonary disease (COPD), asthma, any chronic respiratory/lung disease, chronic heart failure, diabetes, and liver disease or advanced kidney disease.
The safety profile was good, Ison said. Adverse events (AEs) included arm pain, fatigue, headache and myalgia which “usually resolves very quickly”, he added. No imbalance was observed for serious AEs.
The phase III RENOIR trial included 34,284 participants aged 60 and over (mean age 68.3). Walsh presented an interim analysis of the trial with approximately 6 months of follow-up.
For the two-symptom endpoint, 11 cases of lower respiratory tract disease occurred in the treatment group versus 33 in the placebo group, with symptoms including cough, wheezing, sputum production, shortness of breath, throat, nasal congestion and runny nose. For the three-symptom endpoint, two cases occurred in the vaccine arm versus 14 in the controls.
All participants were in good health or had stable chronic medical conditions, Edwards said, and people with immunocompromised conditions were excluded.
Participants had an average age of 68, about 78% were white, 37% Hispanic, 8% were black, and 8% were Asian. The age groups were again well matched: 63% were between 60 and 69, 32% were between 70 and 79, and 6% were 80 and over.
High-risk conditions included chronic cardiopulmonary conditions in 15-16%, asthma in 9%, COPD in 6%, and congestive heart failure in 2%. In addition, 19% suffered from diabetes and 13% from heart disease.
Local reactions, including pain at the injection site, 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% versus 25.7%, respectively – these included local pain at the vaccination site, fatigue, headache, muscle aches, pain joints, diarrhea, fever, nausea and vomiting.
In his presentation, Edwards confirmed the difficulty COVID has caused for the trial, which began in August 2021 at his center.
“It was the worst possible time to conduct an efficacy trial for a non-COVID disease,” he said. “In 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 the AReSVi-006 was funded by GSK.
Walsh reported relationships with Merck and Pfizer. Several co-investigators are employees or shareholders of Pfizer.
Ison declared 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.