Recombinant respiratory syncytial virus (RSV) vaccines for older adults, and pregnant women to prevent disease in their infant

Abrysvo (Pfizer)
Approved indication: active immunisation of pregnant women between 24 and 36 weeks gestation, for prevention of RSV-associated lower respiratory tract disease in their infant from birth through to 6 months of age; and active immunisation of individuals 60 years and older for prevention of RSV-associated lower respiratory tract disease
single-dose vial containing 120 micrograms of RSV pre-fusion F protein antigen (RSVPreF3) powder for reconstitution with supplied diluent

Arexvy (GlaxoSmithKline)
Approved indication: active immunisation of individuals 60 years and older, for prevention of RSV-associated lower respiratory tract disease
single-dose vial containing 120 micrograms of RSV pre-fusion F protein antigen (RSVPreF3) powder for reconstitution with supplied adjuvant suspension

Respiratory syncytial virus (RSV) is a common cause of upper and lower respiratory tract infection. The highest burden of RSV-associated lower respiratory tract disease (LRTD) is among infants and older people; hospitalisation rates decline with age after early childhood, then increase again from 50 to 65 years of age.

Two recombinant RSV protein subunit vaccines (Abrysvo and Arexvy) were recently approved for active immunisation of adults aged 60 years and older. Abrysvo is also approved for active immunisation of pregnant women to prevent RSV disease in their infant from birth through to 6 months of age (RSV neutralising antibodies are transferred across the placenta to the baby in utero). Neither vaccine is approved for active immunisation of infants after birth.^1,2,*

Both vaccines contain the RSV F glycoprotein, in its pre-fusion form (RSVPreF3), which mediates viral fusion and host cell entry. Following administration, RSVPreF3 elicits an immune response, which protects against RSV-associated LRTD. The Abrysvo vaccine is a bivalent vaccine, containing RSVPreF3 from the two major circulating antigenic subgroups RSV-A and RSV-B. The Arexvy is a single-valent vaccine containing RSVPreF3 from an RSV-A strain; it contains an adjuvant to improve immunogenicity.

In adults aged 60 years and older, efficacy of the Abrysvo and Arexvy vaccines has been demonstrated in ongoing, large placebo-controlled clinical trials conducted across multiple countries in both hemispheres.^3,4 In the Abrysvo trial (n=34,284 at interim analysis),³ through one RSV season (mean follow-up 7 months) vaccine efficacy against PCR-confirmed RSV-associated LRTD was 66.7% in older adults with 2 or more symptoms, and 85.7% in older adults with 3 or more symptoms (2 cases in the vaccine group and 14 in the placebo group). In the Arexvy trial (n=24,966 at interim analysis),⁴ through one RSV season (median 6.7 months follow-up) vaccine efficacy against PCR-confirmed RSV-associated LRTD in older adults was 82.6%. Efficacy against severe RSV-related LRTD (assessed on the basis of clinical signs) was 94.1% (one case in the vaccine group and 17 in the placebo group).⁴ Arexvy has also demonstrated moderate vaccine efficacy (67%) against severe disease in older adults across 2 complete RSV seasons in the northern hemisphere (up to 22 months after vaccination).⁵ Both Abrysvo and Arexvy appear to have efficacy against the two major RSV subgroups A and B.^3,4

In pregnant women (for prevention of RSV disease in their infant from birth), efficacy of the Abrysvo vaccine was evaluated in an ongoing placebo-controlled trial conducted across multiple countries in both hemispheres (n=7358 women [median gestation 31.3 weeks], n=7128 infants at interim analysis).⁶ Within 90 days after birth, medically attended severe PCR-confirmed RSV-associated LRTD occurred in 6 infants (0.17%) of women in the vaccine group and 33 infants (0.93%) of women in the placebo group (vaccine efficacy 81.8%). Within 180 days after birth there were 19 (0.53%) and 62 (1.74%) cases of severe LRTD in the vaccine and placebo groups respectively (vaccine efficacy 69.4%).⁶

Common adverse effects for both vaccines, in older adults and pregnant women, included injection-site reactions (pain, redness and swelling), fatigue, myalgia and headache. There was no difference in the rates of serious adverse events in vaccinated people compared with those who received placebo in clinical trials.^3,4,6 Postmarketing studies are underway that may detect rare adverse events.

Administration of both vaccines is by intramuscular injection as a single dose. In older adults, the vaccines can be given at any time of the year, but just before an RSV season may be preferable to optimise protection over at least 2 seasons. Both vaccines can be co-administered with COVID-19 and influenza vaccines in older adults. There is insufficient evidence to determine the need for revaccination.^2,5 In pregnant women, the Abrysvo vaccine can be administered between 24 and 36 weeks gestation (it takes at least 2 weeks after vaccination for RSV neutralising antibodies to develop and be transferred to the baby in utero). Revaccination in subsequent pregnancies has not been studied.² The Arexvy vaccine is not approved for use in pregnant women.

At the time of writing, the Australian Technical Advisory Group on Immunisation (ATAGI) had published recommendations for the Arexvy vaccine only. ATAGI recommended a single dose of the vaccine in the following groups:⁵

• all adults aged 75 years and over
• Aboriginal and Torres Strait Islander peoples aged 60 years and over
• adults aged 60 to 74 years with medical conditions that increase their risk of severe disease due to RSV (e.g. cardiac disease, chronic respiratory disease).

The 2 new RSV vaccines are a significant step forward in the prevention of RSV-associated severe respiratory disease. At the time of writing, Abrysvo is registered but not yet marketed in Australia, and neither RSV vaccine is available on the National Immunisation Program or listed on the Pharmaceutical Benefits Scheme.

* There are 2 RSV monoclonal antibodies approved in Australia for passive immunisation of infants after birth (palivizumab and nirsevimab); at the time of writing these are not widely available.

This new drug comment was finalised on 27 May 2024.

🅃 🅃 manufacturer provided additional useful information. The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.

At the time the comment was prepared, information about these drugs was available on the websites of the Food and Drug Administration in the USA, the European Medicines Agency and the Therapeutic Goods Administration.

 

References

1. Therapeutic Goods Administration. Australian Production Information - AREXVY recombinant respiratory syncytial virus pre-fusion F protein vaccine. Department of Health and Aged Care; 2024. [cited 2024 May 28]
2. Therapeutic Goods Administration. Australian Product Information - ABRYSVO recombinant respiratory syncytial virus pre-fusion F protein bivalent vaccine. Department of Health and Aged Care; 2024. [cited 2024 May 28]
3. Walsh EE, Perez Marc G, Zareba AM, Falsey AR, Jiang Q, Patton M, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med 2023;388:1465-77.
4. Papi A, Ison MG, Langley JM, Lee DG, Leroux-Roels I, Martinon-Torres F, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med 2023;388:595-608.
5. Australian Technical Advisory Group on Immunisation. ATAGI statement on the clinical use of Arexvy (RSV PRE-F3) vaccine for RSV. Department of Health and Aged Care; 2024. [cited 2024 May 6]
6. Kampmann B, Madhi SA, Munjal I, Simoes EAF, Pahud BA, Llapur C, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med 2023;388:1451-64.

 

The new drug commentaries in Australian Prescriber are prepared by the editors and reviewed by the Editorial Advisory Committee. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Advisory Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.