The efficacy of BEQVEZ was evaluated in clinical study 1 (NCT03861273) which is an ongoing, prospective, open-label, single-arm, multi-national study. The study enrolled 45 adult male patients with moderately severe to severe hemophilia B (factor IX activity ≤2 IU/dL). All patients completed a prospective lead-in study of at least six months for baseline data collection while they received routine factor IX prophylaxis in the usual care setting before entering clinical study 1. Enrolled patients then received a single intravenous infusion of BEQVEZ at a dose of 5 × 1011 vg/kg of body weight and entered a follow-up (FU) period of 6 years. Of the 45 patients, 41 completed at least 15 months of FU. The median FU of the 45 treated patients was 2.0 years (range: 0.4 to 3.2 years) from the time of infusion.
Only patients who were negative for pre-existing neutralizing antibodies to AAVRh74var capsid were eligible. Other key exclusion criteria included history of or current inhibitor to factor IX (≥0.6 Bethesda units), active hepatitis B or C infection, HIV infection with CD4 cell count ≤200 mm3 or viral load >20 copies/mL, hypersensitivity to factor IX product, ALT/AST/ALP >2 times ULN, bilirubin >1.5 times ULN, unstable liver or biliary disease, and significant liver fibrosis.
Enrolled patients were 73% White, 16% Asian and 2.2% Black. The median age was 29 years (range: 18 to 62 years). A total of 13 (29%) and 15 (33%) patients had a history of hepatitis B and C, respectively. One (2%) patient was HIV positive.
The main efficacy outcome was a non-inferiority (NI) test of annualized bleeding rate (ABR) during the efficacy evaluation period (EEP), Week 12 (Day 82) to data cutoff following BEQVEZ treatment, compared with baseline ABR during the lead-in period. The ABR included treated and untreated bleeds, excluding procedural bleeds. The NI margin on the difference between the mean EEP ABR and the mean baseline ABR was 3.0 bleeds/year.
Table 5 summarizes the efficacy results. The model derived mean ABR was 4.5 bleeds/year (95% CI: 1.9, 7.2) during the baseline period and 2.5 bleeds/year (95% CI: 1.0, 3.9) during post-BEQVEZ EEP, resulting in a difference between the mean post-BEQVEZ EEP ABR and the baseline ABR of -2.1 bleeds/year (95% CI: -4.8, 0.7). The upper bound of the 95% CI in the difference was less than 3.0 bleeds/year, meeting the NI study success criterion. Six out of 45 patients (13%) resumed routine factor IX prophylaxis after BEQVEZ treatment, starting from 0.4 years to 1.7 years after BEQVEZ infusion. An additional patient had intermittent exogenous factor IX use and had a higher ABR post BEQVEZ (5.0 bleeds/year) compared to baseline (1.2 bleeds/year) with a factor IX activity <5% (SynthASil assay) starting at 0.4 years.
| ABR = Annualized Bleeding Rate for all bleeds (treated and untreated with factor IX, excluding procedural bleeds). | ||
| CI = confidence interval. | ||
| ||
Baseline (Prospective Lead-in Period) | Post-BEQVEZ Efficacy Evaluation Period* | |
Median (range) of follow-up time (years) | 1.2 (0.6, 2.4) | 1.8 (0.2, 3.0) |
Total follow-up time (person-years) | 59 | 83 |
Median (min, max) ABR (bleeds/year)† | 1.3 (0.0, 53.9)‡ | 0.0 (0.0, 19.0) |
4.5 (1.9, 7.2) | 2.5 (1.0, 3.9) | |
n (%) of patients without any bleeds | 13 (29%) | 27 (60%) |
Total number of observed bleeds | 225 | 98 |
Number of observed spontaneous bleeds | 157 (70%) | 60 (61%) |
Number of observed joint bleeds | 184 (82%) | 71 (72%) |
The efficacy of BEQVEZ was evaluated in clinical study 1 (NCT03861273) which is an ongoing, prospective, open-label, single-arm, multi-national study. The study enrolled 45 adult male patients with moderately severe to severe hemophilia B (factor IX activity ≤2 IU/dL). All patients completed a prospective lead-in study of at least six months for baseline data collection while they received routine factor IX prophylaxis in the usual care setting before entering clinical study 1. Enrolled patients then received a single intravenous infusion of BEQVEZ at a dose of 5 × 1011 vg/kg of body weight and entered a follow-up (FU) period of 6 years. Of the 45 patients, 41 completed at least 15 months of FU. The median FU of the 45 treated patients was 2.0 years (range: 0.4 to 3.2 years) from the time of infusion.
Only patients who were negative for pre-existing neutralizing antibodies to AAVRh74var capsid were eligible. Other key exclusion criteria included history of or current inhibitor to factor IX (≥0.6 Bethesda units), active hepatitis B or C infection, HIV infection with CD4 cell count ≤200 mm3 or viral load >20 copies/mL, hypersensitivity to factor IX product, ALT/AST/ALP >2 times ULN, bilirubin >1.5 times ULN, unstable liver or biliary disease, and significant liver fibrosis.
Enrolled patients were 73% White, 16% Asian and 2.2% Black. The median age was 29 years (range: 18 to 62 years). A total of 13 (29%) and 15 (33%) patients had a history of hepatitis B and C, respectively. One (2%) patient was HIV positive.
The main efficacy outcome was a non-inferiority (NI) test of annualized bleeding rate (ABR) during the efficacy evaluation period (EEP), Week 12 (Day 82) to data cutoff following BEQVEZ treatment, compared with baseline ABR during the lead-in period. The ABR included treated and untreated bleeds, excluding procedural bleeds. The NI margin on the difference between the mean EEP ABR and the mean baseline ABR was 3.0 bleeds/year.
Table 5 summarizes the efficacy results. The model derived mean ABR was 4.5 bleeds/year (95% CI: 1.9, 7.2) during the baseline period and 2.5 bleeds/year (95% CI: 1.0, 3.9) during post-BEQVEZ EEP, resulting in a difference between the mean post-BEQVEZ EEP ABR and the baseline ABR of -2.1 bleeds/year (95% CI: -4.8, 0.7). The upper bound of the 95% CI in the difference was less than 3.0 bleeds/year, meeting the NI study success criterion. Six out of 45 patients (13%) resumed routine factor IX prophylaxis after BEQVEZ treatment, starting from 0.4 years to 1.7 years after BEQVEZ infusion. An additional patient had intermittent exogenous factor IX use and had a higher ABR post BEQVEZ (5.0 bleeds/year) compared to baseline (1.2 bleeds/year) with a factor IX activity <5% (SynthASil assay) starting at 0.4 years.
| ABR = Annualized Bleeding Rate for all bleeds (treated and untreated with factor IX, excluding procedural bleeds). | ||
| CI = confidence interval. | ||
| ||
Baseline (Prospective Lead-in Period) | Post-BEQVEZ Efficacy Evaluation Period* | |
Median (range) of follow-up time (years) | 1.2 (0.6, 2.4) | 1.8 (0.2, 3.0) |
Total follow-up time (person-years) | 59 | 83 |
Median (min, max) ABR (bleeds/year)† | 1.3 (0.0, 53.9)‡ | 0.0 (0.0, 19.0) |
4.5 (1.9, 7.2) | 2.5 (1.0, 3.9) | |
n (%) of patients without any bleeds | 13 (29%) | 27 (60%) |
Total number of observed bleeds | 225 | 98 |
Number of observed spontaneous bleeds | 157 (70%) | 60 (61%) |
Number of observed joint bleeds | 184 (82%) | 71 (72%) |
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