Pfizer Announces Positive Top-Line Results from Second Phase 3 Study of 20vPnC in Adults, Demonstrating Consistent Immunogenicity Across Manufacturing Lots

May 14, 2020 /BioonBIOON/ --PfizerPfizer recently announced the top-line results of the second Phase III clinical study (NCT03828617) of its 20-valent pneumococcal polysaccharide conjugate vaccine (20vPnC), PF-06482077. This randomized, open-label study enrolled a total of 1,718 adults aged 18–49 years with no prior history of pneumococcal vaccination, aiming to characterize the safety of three different batches of 20vPnC and to assess the consistency of immune responses.

The results showed that the immune responses elicited by three different batches of 20vPnC vaccination were consistent, meeting the primary immunogenicity endpoint of the study. In this study, the safety profile of 20vPnC was similar to that of the Prevnar 13 (Prevnar 13, 13-valent pneumococcal conjugate vaccine [diphtheria CRM197 protein]) control group. This clinical batch consistency study is expected to satisfy the U.S. Food and Drug Administration (FDA) and other national regulatory authorities' approval requirements for production consistency.

Pfizer plans to announce the full results of the study in the future, following a comprehensive analysis of the safety and immunogenicity data.

Dr. Kathrin U. Jansen, Senior Vice President and Head of Vaccine Research and Development at Pfizer, stated, “We are excited about the progress of the 20vPnC adult development program, as this marks the second Phase III trial to report positive top-line data for this investigational vaccine. These new data underscore Pfizer’s strong legacy, expertise, and proven track record in manufacturing highly complex biological products, such as pneumococcal conjugate vaccines. Demonstrating lot consistency is critical to helping ensure that vaccine recipients receive an equivalent level of protection, regardless of which production lot is administered.”

Streptococcus pneumoniae (S. pneumoniae, image source: paramedicsworld.com)

In March this year, Pfizer announced positive top-line results from the first Phase III study (NCT03760146) of 20vPnC. This randomized, double-blind study enrolled a total of 3,880 adults aged ≥18 years with no prior history of pneumococcal vaccination. The study evaluated the immune response induced by 20vPnC in older adults aged ≥60 years and compared it with the immune responses in control groups receiving either Prevnar 13 or PPSV23 (primary endpoint). The study also assessed20vPnC inThe immune response induced in adults aged 18–59 years (secondary endpoint), and the safety of 20vPnC in all adults aged ≥18 years was described.

The results showed that the study met its primary immunogenicity objective: one month after vaccination, in adults aged ≥60 years, 20vPnC demonstrated non-inferior immunogenicity to all 13 serotypes contained in Prevnar 13 and to 6 of the 7 additional new serotypes contained in PPSV23; for the remaining one of the 7 additional new serotypes in PPSV23, non-inferiority was not met due to a small margin.

Regarding secondary immunogenicity endpoints, the immunogenicity of all 20 serotypes met the non-inferiority criteria in the 18–59 years and 60–64 years age groups. The safety endpoint was met in the overall population aged ≥18 years, demonstrating that the safety and tolerability of 20vPnC were comparable to those of Prevnar 13 and PPSV23.

The key Phase III adult program for 20vPnC includes three Phase III clinical studies (NCT03760146, NCT03828617, NCT03835975), which evaluated the efficacy and safety of the 20vPnC vaccine in preventing invasive disease and pneumococcal pneumonia in adults aged ≥18 years. The three studies enrolled a total of more than 6,000 adults, including those with or without a history of pneumococcal vaccination.

All three studies have been completed, with data from one remaining study (NCT03835975) yet to be published. This study aims to describe the safety and immune response of 20vPnC in adults aged ≥65 years. Pfizer previously stated that it had planned to submit a Biologics License Application (BLA) for the adult indication of 20vPnC to the U.S. Food and Drug Administration (FDA) by the end of 2020.

Pfizer’s 20-valent candidate vaccine, 20vPnC, includes the 13 serotypes contained in Prevnar 13 (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) as well as seven new serotypes (8, 10A, 11A, 12F, 15BC, 22F, and 33F). These seven new serotypes are all global causes of invasive pneumococcal disease, with six of them (8, 10A, 11A, 15BC, 22F, and 33F) associated with high case-fatality rates, and four associated withAntibioticsAssociated with drug resistance (11A, 15BC, 22F, and 33F) and/or meningitis (10A, 15BC, 22F, and 33F).

Globally, pneumococcal pneumonia is estimated to cause approximately 500,000 deaths and 30 million infections annually among adults aged 70 years and older. In summary, the 20 serotypes included in the 20-valent pneumococcal conjugate vaccine (20vPnC) collectively account for the majority of pneumococcal disease currently circulating in the United States and worldwide.

From a regulatory perspective, in September 2018, the U.S. FDA granted Breakthrough Therapy Designation (BTD) to 20vPnC for the prevention of invasive disease and pneumonia in adults aged 18 years and older. In September 2017 and May 2019,FDAFast Track designation was granted separately for 20vPnC for adult and pediatric indications.

Prevnar 13 (沛儿13) is a blockbuster pneumococcal vaccine marketed by Pfizer, with global sales reaching $5.847 billion in 2019.

Prevnar 13 (Pneumovax 13) has been approved: (1) for adults aged ≥18 years, to prevent pneumococcal disease and invasive disease caused by 13 serotypes of Streptococcus pneumoniae; (2) for children aged 6 weeks through 17 years (before their 18th birthday), to prevent invasive disease caused by 13 serotypes of Streptococcus pneumoniae; (3) for children aged 6 weeks through 5 years (before their 6th birthday), to prevent ear infections caused by 7 of the 13 serotypes of Streptococcus pneumoniae.

Prevnar 13 is not 100% effective and can only help prevent the 13 serotypes covered by the vaccine. (Bioon.com)

Original Source: Pfizer Announces Positive Top-Line Results From Phase 3 Lot Consistency Study of 20-Valent Pneumococcal Conjugate Vaccine in Pneumococcal Vaccine-Naive Adults 18 Through 49 Years of Age