Pfizer’s RSV Vaccine Springs Another Surprise, This Time In Maternal Use

Sanofi’s monoclonal antibody is still expected to lead the market in respiratory syncytial virus, but Pfizer may have just overturned expectations about maternal vaccination with its product.

Interim analysis of the Phase IIb study showed 85% efficacy against RSV infection for infants born to vaccinated mothers.

Pfizer Inc has released data from its maternal respiratory syncytial virus (RSV) vaccine candidate which suggest strong efficacy, and could see it take a bigger than expected slice of a soon-to-be multi-billion dollar market.

An abstract from a Phase IIb study being presented at the RSV Vaccines for the World Conference (RSVVW) conference (being held on 10-11 November) marks the first efficacy data from Pfizer’s RSVpreF vaccine, and shows it to reach 85% efficacy protection against RSV infection or hospitalization for infants born to vaccinated mothers.

That rate of protection is better than the 75% achieved by Sanofi and AstraZeneca’s nirsevimab, an antibody-based prophylactic product that is given directly to infants,  in the pivotal Phase III MELODY study earlier this year. (Also see "AstraZeneca And Sanofi March Ahead With Positive Phase III RSV Data" - Scrip, 26 Apr, 2021.)

While cross-trial comparisons are problematic, the results are still eyebrow-raising as the maternal vaccination approach used by Pfizer has failed on numerous earlier occasions, including in a Novavax study which read out in 2019.

Vaccination of a pregnant mother requires a very high level of immunogenicity: enough of the mother’s antibodies must pass through the placenta and remain in the child to provide immune protection in the infant for up to 12 months after birth. 

Novavax’s failure convinced many observers that the approach was a dead end, but Pfizer’s positive results have revived interest. Also being presented at the congress are immunogenicity data from RSVpreF and a Phase II study of another maternal vaccine contender, GSK’s RSVPreF3. Both vaccines induced more than ten-fold increases in RSV-A/B neutralizing antibodies (NAbs) in vaccinated mothers, well above the two- to three-fold increases reported in the Novavax study.

Geoffrey Porges, analyst at SVB Leerink wrote in a 1 November note: “GSK and Pfizer’s results suggest that maternal vaccines could be more attractive than we had anticipated, provided their impressive efficacy holds up in Phase III (and presuming they offer better protection than infant antibody prophylaxis).”

SVB Leerink currently estimates that the infant RSV prophylaxis market could generate $3bn in sales by 2030, and that the new data might help maternal vaccines capture more than a third of the market, versus a two-thirds share for the infant antibodies from Sanofi/AstraZeneca and Merck’s candidate MK-1654.

Sanofi Still Expected To Lead

However, Sanofi is still expected to lead the market, and is gearing up to submit its nirsevimab data with the European Medicines Agency in Q1 2022 and with the US Food and Drug Administration the following quarter.

That should set it up to reach the market by 2023, where analysts expect it to become standard of care (SOC). It is expected to replace the AstraZeneca-developed Synagis (palivizumab), which is used only in pre-term infants where maternal vaccination is unlikely to provide protection,  and have expanded use beyond this population, depending on its final efficacy results and pricing.

Having sounded out physician sentiment on the wave of potential new choices in RSV, the SVB Leerink analysts remarked: “Our conversations with European KOLs suggested on balance a preference for antibodies in that geography, while US KOLs noted both modalities could be adopted if similarly effective. We expect this could become a multi-year debate amongst regulators with variable outcomes across countries.”

A Second Surprise From Pfizer

RSV is not only of the most common causes of hospitalization of infants worldwide, but is also a major cause of hospitalization and mortality in immunocompromised patients and the elderly.

To that end, the pipeline is also bulging with RSV vaccines in adults, with many results expected in 2022.

Pfizer sprang a surprise in this age category too, when in July it announced 100% observed efficacy against mild-to-moderate symptomatic infection in people 60 years in a small challenge study. It followed this up by initiating its pivotal Phase III RENOIR study in this age group in early September, helping it to steal ahead of its main competitors. (Also see "J&J Sets The Pace In Race To $10bn RSV Vaccine Market" - Scrip, 4 Oct, 2021.)

RENOIR is due to read out in Q1 2022, with results expected to be accelerated by a surge in global RSV cases triggered by post-lockdown lifting of social distancing measures.

SVB Leerink predicts the overall RSV market will exceed $7bn by 2030, with consensus estimates forecasting nirsevimab revenues of  €514m by 2025.

Existing consensus estimates for Pfizer’s RSV vaccine across adult and maternal uses are $655m for 2025, most of which is expected from use in adult populations. This figure is likely to be raised following the new data release, and a similar uplift is expected to current projections of £176m for GSK in maternal RSV in 2025 revenues.

 

Given the high level of competition, and flood of results expected next year, there is still much to play for in terms of RSV market share. Two other notable contenders in the field are Moderna, which is using its mRNA platform for its candidate currently in Phase I studies and J&J, which has a vaccine in Phase III, plus its oral antiviral rilematovir in Phase I.