Based on the data presented today, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) believed the benefits outweighed the safety concerns.
The FDA’s VRBPAC met today and voted in favor of the safety and efficacy of the GSK investigational RSV vaccine, RSVPreF3 +AS01E (Arexvy).
The meeting was convened to review the data of the biologics license application (BLA) GSK filed for use of this vaccine for people who are 60 years of age and older for the prevention of lower respiratory tract disease (LRTD).
At today’s meeting, The committee voted on two questions looking at the safety and effectiveness of the vaccine for seniors.
VRBPAC members were instructed to vote “Yes” or “No” on the following 2 questions:
Question #1: Are the available data adequate to support the safety of Arexvy (RSVPreF3 +AS01E ) Vaccine when administered to individuals 60 years of age and older for the prevention of lower respiratory tract disease caused by RSV?
Question #2: Are the available data adequate to support the effectiveness of Arexvy (RSVPreF3 +AS01E ) Vaccine for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older?
The voting results for Question #1 were: 10 members voted yes, 2 members voted no, and 0 members abstained.
The voting results for Question #2 were: 12 members voted yes, 0 members voted no, and 0 members abstained.
GSK Vaccine Safety Profile
Peggy Webster, MD, MBA, vice president & head of vaccine safety, GSK presented information of the safety profile and adverse effects of the vaccine.
There were five phase 3 studies. The most common local events reported pain at the injection site, erythema, and fever. “Most of the systemic events were mild in severity and resolved quickly,” Webster said in her presentation.
GSK reported 3 Grade 3 AEs in the studies. There was 1 case of Guillain Barre Syndrome (GBS) and there were 2 cases of acute disseminated encephalomyelitis (ADEM).
For the GBS case, the following was reported:
There was 1 case of GBS in a 78 year-old female. She had an elevated CSF protein, serum GM1-IgG positive, and BC Level 3. Her condition was considered resolved after a hospital stay and treatment.
For the ADEM cases, the following was reported:
One case was a 71 year-old female and no investigations were performed. This was a BC Level 3 and the participant was not considered resolved at the time of reporting.
There was one other case and that was a 71 year-old male who had 2 prior strokes with Wallerian demyelination. This was a BC Level 3 and he had a fatal outcome.
In his presentation, Nicholas Geagan, DO, FDA/CBER Office of Vaccines Research and Review Division of Vaccines and Related Products Applications, reviewed the efficacy and safety data. He mentioned the 3 aforementioned adverse events, and mentioned the case of the fatal outcome. In a slide in his presentation, he noted the one death due to ADEM was considered by FDA as possibly related to the influenza or RSVPreF3 vaccine.
It is important to note, both cases of ADEM occurred in study 007, where an influenza vaccine was given concurrently with the GSK RSV vaccine. In Study 007 there were 890 vaccinees.
Study 007 was a concomitant administration with the GSK vaccine and FLU-QIV (Fluarix Quadrivalent). It had a total of 885 participants who were randomized 1:1 to one of two study groups:
No cases of ADEM were observed in Study 006, which was the largest of the five clinical studies, or the others outside of Study 007. There were 12,467 RSV vaccines administered in Study 006, and there were 2370 vaccinees in other studies.
Webster said they will continue to monitor for any adverse events in post-marketing. “The benefits outweigh the risk,” Webster said in conclusion of her presentation.
During the afternoon Q&A with GSK, the committee members asked a variety of questions surrounding the safety, adverse events, and the make-up of the vaccine and if that had any connection to some of the AEs.
Hana El Sahly, MD, chair, VRBPAC Professor, Department of Molecular Virology and Microbiology Baylor College of Medicine, who served as the host of the VRBPAC meeting had concerns on the GBS risks, and expressed the aforementioned desire of post-marketing data to help inform adverse events and safety. She voted no on the first question, but yes on the second question.
Vaccine efficacy against severe RSV lower respiratory tract disease (RSV-LRTD), defined by at least 2 lower respiratory signs or otherwise assessed as severe, was 94.1%. Efficacy against first occurrence was 82.6%. Among participants with preexisting comorbidities, including cardiorespiratory or endocrinometabolic conditions, vaccine efficacy was 94.6%. For adults 70-79 years of age, vaccine efficacy was 93.8%. This observed vaccine effectiveness was consistent for both RSV-A and RSV-B subtypes, with respective efficacies of 84.6% and 80.9%.
As this is an older patient population, it was pointed out that there is a big difference in a patient population on the younger side (60-year-olds) vs a frail, older population who might be in their late 70s or 80s.
To find out more about the data and efficacy, check out this Contagion interview with Michael Ison, MD, MS, who studied the vaccine.
This VRBPAC meeting was the first step in deciding upon the GSK vaccine. The next stop for the vaccine is for the FDA to take the VRBPAC’s recommendation and decide if they want to move forth with the GSK vaccine for administration to the indicated audience.