Pfizer announced positive top-line data from the phase III clinical trial, MATISSE (MATernal Immunization Study for Safety and Efficacy), investigating its bivalent RSV prefusion vaccine candidate, RSVpreF or PF-06928316, when administered to pregnant participants to help protect their infants from RSV disease after birth.
The preplanned, interim efficacy analysis conducted by an external and independent Data Monitoring Committee (DMC) met the success criterion for one of two primary endpoints. The observed efficacy for severe medically attended lower respiratory tract illness (severe MA-LRTI) was 81.8% (CI: 40.6%, 96.3%) through the first 90 days of life. Substantial efficacy of 69.4% (CI: 44.3%, 84.1%) was demonstrated for infants over the 6-month follow-up period.
Although the statistical success criterion was not met for the second primary endpoint, clinically meaningful efficacy was observed for MA-LRTI of 57.1% (CI: 14.7%, 79.8%) in infants from birth through the first 90 days of life. Efficacy for MA-LRTI of 51.3% (CI: 29.4%, 66.8%) was observed over the 6-month follow-up period.
Preplanned safety reviews conducted at regular intervals throughout the duration of the study by the DMC also indicate the investigational vaccine is well-tolerated, with no safety concerns for both the vaccinated individuals and their newborns.
MATISSE is a randomized, double-blinded, placebo-controlled phase III study designed to assess the efficacy, safety, and immunogenicity of RSVpreF against MA-LRTI and severe MA-LRTI in infants born to healthy women vaccinated during pregnancy. The study enrolled around 7,400 pregnant women. Study participants aged 49 years and younger were randomized in a 1:1 ratio to receive a single dose of either 120 mcg of Pfizer’s RSVpreF or placebo during the late second to third trimester of their pregnancy. The trial also evaluated safety throughout the study and immunogenicity of the vaccine in pregnant women and their infants.
The study participants were followed for safety through vaccination and for 6 months after delivery. Infants were followed for at least 1 year for safety and efficacy, with over one-half of the infants followed for 2 years. This was a global study in 18 countries starting in June 2020, so it spanned multiple RSV seasons in both the northern and southern hemisphere. The manufacturer plans to submit these results for peer-review in a scientific journal.
On March 2, 2022, Pfizer announced that its vaccine candidate received Breakthrough Therapy Designation from the FDA for the prevention of RSV-associated lower respiratory tract disease in infants up to age 6 months by active immunization of pregnant women. The FDA designation was informed by the results of the phase IIb proof-of-concept study of RSVpreF, which evaluated the safety, tolerability, and immunogenicity of RSVpreF in vaccinated pregnant women aged 18 through 49 years and their infants. This followed the FDA’s November 2018 decision to grant Fast Track status to RSVpreF.
Annaliesa Anderson, PhD, senior VP and chief scientific officer of vaccine research and development at Pfizer, stated, “We are thrilled by these data as this is the first-ever investigational vaccine shown to help protect newborns against severe RSV-related respiratory illness immediately at birth. These data reinforce Pfizer’s resolve to bring our expertise in the research and development of innovative vaccines to address critical public health needs using new approaches and technologies. We look forward to working with the FDA and other regulatory agencies to bring this vaccine candidate to expectant mothers to help protect their infants against severe RSV during their most vulnerable first six months of life, which has the highest burden of RSV illness in infants. We would like to thank the pregnant women who volunteered for this trial, along with their infants, and all the investigators around the world who participated in the study for their contribution to this landmark research.”
At the recommendation of the DMC, and in consultation with the FDA, the manufacturer has halted enrollment in the study. Based on these positive results, the manufacturer intends to submit a Biologics License Application to the FDA by the end of 2022 for the vaccine candidate, followed by other regulatory authorities in the coming months.
Eric A.F. Simões, MD, clinical professor of pediatrics-infectious diseases at the University of Colorado School of Medicine and Children’s Hospital Colorado in Aurora, stated, “Every year we see high levels of RSV cases among babies in the U.S. with some regions reporting hospital admission rates higher than normal this year. A maternal vaccine with high efficacy that can help protect infants from birth could substantially reduce the burden of severe RSV among newborns through six months of age, and, if approved by regulatory authorities, will likely have a significant impact on disease in the U.S. and globally.”
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Published November 11, 2022