Pfizer: Pfizer Announces Positive Top-Line Data of Phase 3 Global Maternal Immunization Trial for its Bivalent Respiratory Syncytial Virus (RSV) Vaccine Candidate

Pfizer Inc. (NYSE: PFE) today announced positive top-line data from the Phase 3 clinical trial (NCT04424316) 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 pre-planned, 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 six-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 six-month follow up period.

Pre-planned 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.

“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,” said Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer, Vaccine Research & Development, Pfizer. “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 U.S. Food and Drug Administration (FDA), Pfizer has stopped enrollment in the study. Based on these positive results Pfizer plans to submit a Biologics License Application (BLA) to the FDA by the end of 2022 for the vaccine candidate followed by other regulatory authorities in the coming months.

“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,” said Eric A.F. Simões, M.D., Clinical Professor, Pediatrics-Infectious Diseases, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora. “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.”

MATISSE is an ongoing randomized, double-blinded, placebo-controlled Phase 3 study designed to evaluate the efficacy, safety, and immunogenicity of RSVpreF against medically attended lower respiratory tract illness (MA-LRTI) and severe MA-LRTI in infants born to healthy women vaccinated during pregnancy. The study enrolled approximately 7,400 pregnant individuals. Maternal participants ≤ 49 years of age were randomized in a 1:1 ratio to receive a single dose of either 120 µg of Pfizer’s RSVpreF or placebo during the late second to third trimester of their pregnancy. The trial also assessed safety throughout the study and immunogenicity of the vaccine in pregnant individuals and their infants. Maternal participants were followed for safety through vaccination and for six months after delivery. Infants were followed for at least one year for safety and efficacy, with over half of the infants followed for two years. This was a global study in 18 countries and started in June 2020, so it spanned multiple RSV seasons in both the northern and southern hemisphere.

Pfizer intends 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 six months of age by active immunization of pregnant women. The FDA designation was informed by the results of the Phase 2b proof-of-concept study of RSVpreF (NCT04032093), which evaluated the safety, tolerability and immunogenicity of RSVpreF in vaccinated pregnant women ages 18 through 49 and their infants. This followed the FDA’s November 2018 decision to grant Fast Track status to RSVpreF.

Burden of RSV in Infants
RSV is a contagious virus and a common cause of respiratory illness.1 The virus can affect the lungs and breathing passages of an infected individual and can be potentially life-threatening for young infants, persons with certain chronic medical conditions, and older adults.2,3,4,5 In the United States alone, approximately 2.1 million outpatient visits and 58,000 hospitalizations due to RSV occur each year among children younger than five years old.6,7 Worldwide, RSV results in death of approximately 102,000 children annually, with about half of those in infants less than 6 months old and the vast majority in developing countries.8,9

RSV bronchiolitis is the leading cause of infant hospitalization due to viral respiratory illness, characterized by respiratory distress that can result in death. There is no specific treatment for RSV, only supportive care measures like oxygen and fluids. Currently there is no vaccine to prevent RSV. The only available preventive agent is recommended for use in limited settings in the highest-risk infants as a monthly injection with 5 doses administered during the RSV season, leaving most infants without protection.