HOT OFF THE PRESS

First respiratory syncytial virus (RSV) vaccine approved for older adults

News Alert:

• On May 4, 2023 GlaxoSmithKline (GSK) received United States (US) Food and Drug Administration (FDA) approval for respiratory syncytial virus vaccine, adjuvanted ( Arexvy) for active immunization for the prevention of lower respiratory tract disease (LRTD) caused by RSV in adults ≥ 60 years of age

• This communication is preliminary based on information available at this time

Highlights:

• First vaccine approved in the US to prevent LRTD caused by RSV in ages ≥ 60 years

• Vaccine platform: recombinant prefusion RSV glycoprotein F (RSVPreF3) antigen with AS01E adjuvant

• Dosage form: 2 components – preservative-free 120 µg of lyophilized RSVPreF3 antigen for reconstitution packaged with the AS01E adjuvant suspension

• Dosing: Arexvy is administered as a single 120 µg (0.5 mL) intramuscular (IM) dose

• Approval is based on an ongoing, randomized (1:1), multinational, phase 3 trial. Nearly 25,000 adults ≥ 60 years of age received a single-dose IM injection of Arexvy 120 µg or placebo:

» Vaccine efficacy (VE) for Arexvy was 82.6% against laboratory-confirmed RSV LRTD and 94.1% against severe RSV LRTD

» VE against LRTD RSV varied by age: 81% VE among those 60 to 69 years and 93.8% in ages 70 to 79 years

• Safety

» Common adverse reactions in clinical studies included injection site pain, fatigue, myalgia, headache, and arthralgia

» Notably, among vaccine recipients in other studies, 1 case of Guillain-Barré syndrome considered to be related to vaccination occurred 9 days after Arexvy administration. Acute disseminated encephalomyelitis (ADEM) occurred 7 to 22 days after the dose in 2 participants given Arexvy and concomitant seasonal influenza vaccine (Fluarix Quadrivalent). One ADEM event was fatal. Within 30 days of vaccination, atrial fibrillation was reported in 10 participants who received Arexvy and 4 in the placebo group, though a causal relationship has not been determined

Market Dynamics:

• Availability: Prior to the 2023-2024 RSV season

• Cost: To be determined

• The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) is expected to convene in June 2023 to make recommendations on the appropriate use of RSV vaccines. Once ACIP’s recommendations are approved by the CDC Director and appear on CDC immunization schedules, generally, they must be covered by applicable plans

Market Impact:

RSV is a common contagious respiratory virus that usually causes mild, cold-like symptoms. However, serious illnesses, such as bronchiolitis and pneumonia, may develop in some individuals and may require hospitalization. Individuals particularly at risk for serious RSV illness include infants and older adults. In the US, RSV causes 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths each year among adults ages ≥ 65 years. RSV is also a leading cause of hospitalization in infants.

The RSV season in the US typically occurs from approximately November through April but may vary by region. Both RSV subtypes A and B tend to co-circulate during each season. Notably, in 2021-2022, the usual RSV seasonal circulating pattern was disrupted during the Coronavirus Disease 2019 (COVID-19) pandemic. In 2022-2023, RSV circulation began to revert toward the pre-COVID-19 pandemic pattern but with a higher intensity of circulation.

There is no FDA-approved medication to treat RSV infection. Moreover, RSV infection does not impart lasting immunity and re-infections can occur. The approval of GSK’s Arexvy marks the first-ever vaccine to prevent LRTD due to RSV infection in adults ≥ 60 years of age. Postmarketing studies to assess safety risks for Guillain-Barré and ADEM (FDA-required) and atrial fibrillation (not FDA-required) will be conducted.

A GSK vaccine study in adults ≥ 60 years of age is ongoing and will provide potential data on use as an annual single-dose revaccination over multiple RSV seasons. GSK is also testing the RSV vaccine in ages 50 to 59 years.

FDA decision for Pfizer’s RSV vaccine candidate (in ages ≥ 60 years) is expected later this month. Moderna is expected to apply for its mRNA RSV vaccine for older adults in the upcoming months.

Looking ahead at the pipeline, Pfizer is seeking approval for RSV maternal administration vaccine to protect infants, with an FDA decision expected in August 2023. GSK stopped its maternal vaccine study due to safety concerns. If approved, future combination vaccines that are being studied could potentially mitigate vaccine hesitancy. Furthermore, nirsevimab, AstraZeneca/Sanofi’s single-dose monoclonal antibody for protecting infants from RSV, is slated for approval in 3rd quarter of 2023.

References:

• FDA News Release: https://www.fda.gov/news-events/press-announcements/fda-approves-first-respiratorysyncytial-virus-rsv-vaccine. Accessed May 3, 2023.

• GlaxoSmithKline Press Release: https://www.gsk.com/en-gb/media/press-releases/us-fda-approves-gsk-s-arexvythe-world-s-first-respiratory-syncytial-virus-rsv-vaccine-for-older-adults/. Accessed May 3, 2023.

• Arexvy [package insert]. Durham, NC; GlaxoSmithKline. May 2023.

• Vaccines and Related Biological Products Advisory Committee Meeting March 1, 2023. Respiratory Syncytial Virus Vaccine Recombinant, Adjuvanted (Proposed Trade Name: Arexvy). https://www.fda.gov/media/165622/ download. Accessed May 2, 2023.

• GSK. RSVPreF3 OA. Sponsor briefing document. Vaccines and related biological products advisory committee. Meeting: February 29-March 1, 2023. https://www.fda.gov/media/165621/download. Accessed May 2, 2023.

• Papi A, Ison MG, Langley JM, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med 2023; 388:595-608. DOI: 10.1056/NEJMoa2209604.

• CDC. Respiratory syncytial virus infection (RSV). RSV surveillance & research. Reviewed October 28, 2022. https:// www.cdc.gov/rsv/research/index.html. Accessed May 2, 2023.

• CDC MMWR. Seasonality of Respiratory Syncytial Virus — United States, 2017–2023. https://www.cdc. gov/mmwr/volumes/72/wr/mm7214a1.htm#:~:text=The%202022%E2%80%9323%20epidemic%20 began,suggesting%20higher%20intensity%20of%20circulation. Accessed May 2, 2023.

Editorial Staff

Maryam Tabatabai, PharmD Vice President, Clinical Information

Carole Kerzic, RPh Clinical Pharmacist, Drug Information

Devon Trumbower, PharmD, BCPS Clinical Pharmacist, Drug Information