WASHINGTON — Prefusion F protein vaccine candidates for respiratory syncytial virus (RSV) proved safe in adults 60 and up while demonstrating an ability to thwart lower respiratory tract illness, including severe cases, a pair of large phase III trials showed.
A single dose of an RSV prefusion F protein vaccine (RSVPreF3 OA) yielded a vaccine efficacy of 82.6% against lower respiratory tract illness (96.95% CI 57.9-94.1), meeting the study’s primary endpoint, and vaccine efficacy landed at 94.1% against severe RSV illness (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 an efficacy of 66.7% against two or more lower respiratory tract RSV symptoms (96.66% CI 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 the study, according to Edward Walsh, MD, of the University of Rochester in New York.
Currently, no vaccines exist to protect against RSV infection. According to data from the CDC, an estimated 177,000 older adults in the US were hospitalized due to RSV infections in 2017 alone, and 14,000 died.
“For someone that’s been working in the field for a very long time, I could not be more excited about the advances we’re seeing, particularly with the respiratory syncytial virus vaccines,” said session moderator Kathleen Neuzil, MD, of the University of Maryland in Baltimore, introducing the anticipated trials.
The phase III AReSVi-006 (Adult Respiratory Syncytial Virus) trial of RSVPreF3 OA presented by Ison included 24,960 adults age 60 and older (mean 69.5 years) who were randomized 1:1 to the vaccine or placebo. 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 individuals who received the vaccine developed lower respiratory tract illness from RSV versus 40 among placebo recipients.
Severe cases involved at least two lower respiratory signs or assessed as severe by the investigator and confirmed by the external adjudication committee, or was based on use of supportive therapy. One case of severe lower respiratory tract illness occurred in the vaccine group and 17 occurred in the placebo group.
The treatment and placebo groups were similarly matched for age: 56% were 60-69 years, 36% age 70-79 years, and 8% were 80 and older. Most 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 up, and people who were frail, too few cases occurred to assess efficacy, according to Ison. Efficacy against lower respiratory tract illness appeared consistent regardless of comorbidity status (72.5% for none and 94.6% for one or more) and was 92.9% for those deemed pre-frail and 80% for those deemed fit.
Baseline comorbidities were reported in just under 40% of participants, and included chronic obstructive pulmonary disease (COPD), asthma, any chronic respiratory/pulmonary disease, chronic heart failure, diabetes, and advanced liver or renal disease.
The safety profile was good, Ison said. Adverse events (AEs) included arm pain, fatigue, headache, and myalgia that “typically resolved very quickly,” he added. No imbalances were seen for serious AEs.
The phase III RENOIR trial included 34,284 participants age 60 and up (mean age 68.3 years). Walsh presented an interim analysis of the trial with about 6 months of 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, sore throat, nasal congestion, and nasal discharge. 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 immunocompromising conditions were excluded.
Participants had a mean age of 68 years, about 78% were white, 37% Hispanic, 8% were Black, and 8% were Asian. Age groups again were well matched: 63% were ages 60-69 years, 32% were 70-79 years, and 6% were 80 and up.
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, including injection site pain, redness, and swelling were seen in 12.1% of the treatment group versus 6.6% of the placebo group. AEs overall were seen in 27.4% versus 25.7%, respectively — these included local pain at the site of vaccination, fatigue, headache, muscle pain, joint pain, diarrhea, fever, nausea, and vomiting.
In his presentation, Edwards confirmed the difficulty COVID caused for the trial, which started in August 2021 at his center.
“This was the worst possible time to run an efficacy trial for non-COVID illness,” 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 Pfizer employees or shareholders.
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. Multiple co-investigators are GSK employees or shareholders.
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