On Oct. 6, 2020, Pfizer and BioNTech announced the initiation of a rolling submission to the European Medicines Agency (EMA) for BNT162b2, the lead candidate from the companies’ vaccine development program against COVID-19. The EMA’s decision to start a rolling review follows the encouraging preliminary results from pre-clinical and early clinical studies in adults, which suggest that BNT162b2 triggers the production of neutralizing antibodies and TH-1 dominant CD4+ and CD8+ T cells that target SARS-CoV-2. A combination of an antibody and T cell response is believed to be important in eliciting protection against viral infection and disease. BioNTech and Pfizer plan to work with the EMA’s Committee for Medicinal Products for Human Use (CHMP) to complete the rolling review process to facilitate the final Marketing Authorization Application (MAA).

As part of the rolling review, the CHMP has begun evaluating data generated in pre-clinical trials. The formal MAA submission could be finalized following the rolling review process, pending demonstration of vaccine efficacy and safety and confirmation from the EMA that the submitted data are adequate. The vaccine candidate will remain subject to the EMA’s diligent standards for quality, safety and efficacy.

The BNT162b2 vaccine candidate is based on BioNTech’s proprietary mRNA technology and supported by Pfizer’s global vaccine development and manufacturing capabilities. It encodes an optimized SARS-CoV-2 full-length spike glycoprotein (S), which is a target of virus neutralizing antibodies. The vaccine candidate is currently being evaluated in a global Phase 3 study ongoing at more than 120 clinical sites worldwide including the United States, Brazil, South Africa and Argentina. To date, the trial has enrolled approximately 37,000 participants with more than 28,000 having received their second vaccination.

Preliminary data from the Phase 1/2 portions of the study have demonstrated that BNT162b2 was well tolerated with mild to moderate adverse events in all age groups. The vaccine candidate generated dose level-dependent immunogenicity, as measured by receptor binding domain (RBD)-binding IgG concentrations and SARS-CoV-2 neutralizing titers. In addition, BNT162b2-vaccinated human participants displayed a favorable breadth of epitopes recognized in T cell responses specific to the SARS-CoV-2 spike antigen, and BNT162b2 demonstrated a concurrent induction of high magnitude CD4+ and CD8+ T cell responses which were TH-1 dominant against the RBD and the remainder of the full spike glycoprotein.

Normally, all data on an investigational medicine’s efficacy, safety and quality and all required documents must be submitted at the start of the evaluation in a complete application for marketing authorization. In the case of a rolling review, the EMA’s CHMP reviews data as they become available from ongoing studies, before a complete application is submitted. Once the CHMP decides that sufficient data are available, the complete application should be submitted by the company. By reviewing the data as they become available, the CHMP can reach its opinion sooner on whether or not the investigational medicine or vaccine should be authorized. After a positive opinion, if adopted by the CHMP, it is the European Commission’s role to grant a Marketing Authorization.