Vaccine Information: Comirnaty (Page 4 of 8)

14.2 Primary Series With COMIRNATY – Efficacy in Participants 16 Years of Age and Older

Study 2 is an ongoing, multicenter, multinational, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate–selection, and efficacy study in participants 12 years of age and older. Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, were included as were participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).

In Study 2, based on data accrued through March 13, 2021, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of COMIRNATY or placebo. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.

Overall, among the total participants who received COMIRNATY or placebo, 51.4% or 50.3% were male and 48.6% or 49.7% were female, 79.1% or 79.2% were 16 through 64 years of age, 20.9% or 20.8% were 65 years of age and older, 81.9% or 82.1% were White, 9.5% or 9.6% were Black or African American, 1.0% or 0.9% were American Indian or Alaska Native, 4.4% or 4.3% were Asian, 0.3% or 0.2% Native Hawaiian or other Pacific Islander, 25.6% or 25.4% were Hispanic/Latino, 73.9% or 74.1% were non-Hispanic/Latino, 0.5% or 0.5% did not report ethnicity, 46.0% or 45.7% had comorbidities [participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease: defined as subjects who had at least 1 of the Charlson comorbidity index category or body mass index (BMI) ≥30 kg/m² ], respectively. The mean age at vaccination was 49.8 or 49.7 years and median age was 51.0 or 51.0 in participants who received COMIRNATY or placebo, respectively.

Efficacy Against COVID-19

The population for the analysis of the protocol pre-specified primary efficacy endpoint included 36,621 participants 12 years of age and older (18,242 in the COMIRNATY group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. The population in the protocol pre-specified primary efficacy analysis included all participants 12 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 through November 14, 2020. Participants 18 through 55 years of age and 56 years of age and older began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020.

For participants without evidence of SARS-CoV-2 infection prior to 7 days after Dose 2, vaccine efficacy against confirmed COVID-19 occurring at least 7 days after Dose 2 was 95.0% (95% credible interval: 90.3, 97.6), which met the pre-specified success criterion. The case split was 8 COVID-19 cases in the COMIRNATY group compared to 162 COVID-19 cases in the placebo group.

The population for the updated vaccine efficacy analysis included participants 16 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 during blinded placebo-controlled follow-up through March 13, 2021, representing up to 6 months of follow-up after Dose 2. There were 12,796 (60.8%) participants in the COMIRNATY group and 12,449 (58.7%) in the placebo group followed for ≥4 months after Dose 2 in the blinded placebo-controlled follow-up period.

SARS-CoV-2 variants of concern identified from COVID-19 cases for this age group from this data cutoff include B.1.1.7 (Alpha) and B.1.351 (Beta). Representation of identified variants among cases in vaccine versus placebo recipients did not suggest decreased vaccine effectiveness against these variants.

The updated vaccine efficacy information is presented in Table 13.

Table 13: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Age Subgroup – Participants 16 Years of Age and Older Without Evidence of Infection and Participants With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population During the Placebo-Controlled Follow-up Period

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2) and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis. † Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original). ‡ N = Number of participants in the specified group. § n1 = Number of participants meeting the endpoint definition. ¶ Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period. # n2 = Number of participants at risk for the endpoint. Þ Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the surveillance time.
First COVID-19 occurrence from 7 days after Dose 2 in participants Without evidence of prior SARS-CoV-2 infection *
Subgroup	COMIRNATY † N ‡ =19,993 Cases n1 § Surveillance Time ¶ (n2 # )	Placebo N ‡ =20,118 Cases n1 § Surveillance Time ¶ (n2 # )	Vaccine Efficacy % (95% CI Þ )
All participants	776.092 (19,711)	8335.857 (19,741)	91.1(88.8, 93.1)
16 through 64 years	704.859 (15,519)	7094.654 (15,515)	90.5(87.9, 92.7)
65 years and older	71.233 (4192)	1241.202 (4226)	94.5(88.3, 97.8)
First COVID-19 occurrence from 7 days after Dose 2 in participants With or without * evidence of prior SARS-CoV-2 infection
Subgroup	COMIRNATY † N ‡ =21,047 Cases n1 § Surveillance Time ¶ (n2 # )	Placebo N ‡ =21,210 Cases n1 § Surveillance Time ¶ (n2 # )	Vaccine Efficacy % (95% CI Þ )
All participants	816.340 (20,533)	8546.110 (20,595)	90.9(88.5, 92.8)
16 through 64 years	745.073 (16,218)	7264.879 (16,269)	90.2(87.5, 92.4)
65 years and older	71.267 (4315)	1281.232 (4326)	94.7(88.7, 97.9)

Subgroup analyses of vaccine efficacy (although limited by small numbers of cases in some subgroups) did not suggest meaningful differences in efficacy across genders, ethnic groups, geographies, or for participants with obesity or medical comorbidities associated with high risk of severe COVID-19.

Efficacy Against Severe COVID-19

Efficacy analyses of secondary efficacy endpoints supported the benefit of COMIRNATY in preventing severe COVID-19. Vaccine efficacy against severe COVID-19 is presented only for participants with or without prior SARS-CoV-2 infection (Table 14) as the COVID-19 case counts in participants without prior SARS-CoV-2 infection were the same as those in participants with or without prior SARS-CoV-2 infection in both the COMIRNATY and placebo groups.

Table 14: Vaccine Efficacy – First Severe COVID-19 Occurrence in Participants 16 Years of Age and Older With or Without * Prior SARS-CoV-2 Infection Based on Protocol † or Centers for Disease Control and Prevention (CDC)‡ Definition From 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population During the Placebo-Controlled Follow-up

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting).
* Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2) and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis. † Severe illness from COVID-19 is defined in the protocol as confirmed COVID-19 and presence of at least 1 of the following:• Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per minute, saturation of oxygen ≤93% on room air at sea level, or ratio of arterial oxygen partial pressure to fractional inspired oxygen <300 mm Hg);• Respiratory failure [defined as needing high flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)];• Evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or requiring vasopressors);• Significant acute renal, hepatic, or neurologic dysfunction;• Admission to an Intensive Care Unit;• Death. ‡ Severe illness from COVID-19 as defined by CDC is confirmed COVID-19 and presence of at least 1 of the following:• Hospitalization;• Admission to the Intensive Care Unit;• Intubation or mechanical ventilation;• Death. § Vaccine encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original). ¶ n1 = Number of participants meeting the endpoint definition. # Total surveillance time in 1000 person-years for the given endpoint across all participants within each group at risk for the endpoint. Time period for COVID-19 case accrual is from 7 days after Dose 2 to the end of the surveillance period. Þ n2 = Number of participants at risk for the endpoint. ß Two-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the surveillance time.
Vaccine Efficacy – First Severe COVID-19 Occurrence
	COMIRNATY § Cases n1 ¶ Surveillance Time # (n2 Þ )	Placebo Cases n1 ¶ Surveillance Time # (n2 Þ )	Vaccine Efficacy % (95% CI ß )
7 days after Dose 2ß	16.353 (20,540)	216.237 (20,629)	95.3(70.9, 99.9)
Vaccine Efficacy – First Severe COVID-19 Occurrence Based on CDC Definition
	COMIRNATY § Cases n1 ¶ Surveillance Time # (n2 Þ )	Placebo Cases n1 ¶ Surveillance Time # (n2 Þ )	Vaccine Efficacy % (95% CI ß )
7 days after Dose 2ß	06.345 (20,513)	316.225 (20,593)	100(87.6, 100.0)