Drug Trials Snapshots - HYMPAVZI
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the HYMPAVZI Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
HYMPAVZI (marstacimab)
him-PAV-zee
Pfizer Inc.
Original Approval date: October 11, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
HYMPAVZI is a drug used to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A or hemophilia B. It is to be used in patients who have not developed an immune response known as factor VIII or factor IX inhibitors or antibody.
Hemophilia A and hemophilia B are inherited blood-clotting disorders that affect primarily males. It is caused by missing or abnormal clotting protein (factor VIII in hemophilia A) or (factor IX in hemophilia B) that make it more difficult to stop bleeding.
How is this drug used?
HYMPAVZI is a preventative (prophylactic) treatment injected under the skin (subcutaneous injection), with a first dose (loading dose) of HYMPAVZI of 300 mg (two 150 mg injections), followed by a weekly dose of 150 mg injection under the skin.
Who participated in the clinical trials?
The FDA approved HYMPAVZI based on evidence from a one clinical trial, BASIS (NCT03938792), which included 116 adults and pediatric patients 12 years of age and older with hemophilia A (congenital factor VIII deficiency) without factor VIII inhibitors and hemophilia B (congenital factor IX deficiency) without factor IX inhibitors. The trial was conducted at 52 sites in 19 countries in Bulgaria, Canada, China, Croatia, France, Hong Kong, India, Italy, Japan, Republic of Korea, Mexico, Oman, Russian Federation, Saudi Arabia, Serbia, South Africa, Spain, Turkey, and the United States. There was one patient from the United States and 115 patients from outside the United States enrolled in the trial.
How were the trials designed?
BASIS enrolled patients 12 years of age and older, weighing at least 35 kg, with hemophilia A or hemophilia B, without inhibitors.
Patients who were receiving factor on-demand treatment at the start of the trial continued to receive factor on-demand for a 6-month observation period and then were switched to receive HYMPAVZI prophylaxis for a 12-month treatment period (Observation On-Demand Group). Patients who were receiving factor prophylaxis at the start of the trial continued to receive factor prophylaxis for a 6-month observation period and then were switched to receive HYMPAVZI prophylaxis for a 12-month treatment period (Observation Prophylaxis Group).
The benefit of HYMPAVZI was assessed in BASIS by comparing the number of bleeding episodes that required treatment when receiving HYMPAVZI compared to the number of bleeding episodes that required treatment when receiving factor, either on-demand or prophylaxis.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the BASIS study used to evaluate the safety and efficacy of HYMPAVZI.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the BASIS study used to evaluate the safety and efficacy of HYMPAVZI.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the BASIS study used to evaluate the safety and efficacy of HYMPAVZI.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity were enrolled in the BASIS study used to evaluate the safety and efficacy of HYMPAVZI.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, BASIS
| Characteristic | Observation On-Demand Group N=33 | Observation Prophylaxis Group N=83 | All Patients N=116 |
|---|---|---|---|
| Sex, n (%) | |||
| Male | 33 (100) | 83 (100) | 116 (100) |
| Age, years | |||
| Mean (SD) | 31.9 (11.04) | 32.6 (14.81) | 31.9 (13.8) |
| Median (min, max) | 29 (15, 58) | 31 (13, 66) | 29 (12, 66) |
| Age group, years, n (%) | |||
| <18 | 2 (6.1) | 17 (20.5) | 19 (16.4) |
| 18 to 44 | 27 (81.8) | 43 (51.8) | 70 (60.3) |
| 45 to 64 | 4 (12.1) | 22 (26.5) | 26 (22.4) |
| 65 to 74 | 0 | 1 (1.2) | 1 (0.9) |
| Race, n (%) | |||
| Asian | 22 (66.7) | 36 (43.4) | 58 (50.0) |
| Black or African American | 0 | 1 (1.2) | 1 (0.9) |
| White | 11 (33.3) | 45 (54.2) | 56 (48.3) |
| Missing | 0 | 1 (1.2) | 1 (0.9) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 3 (9.1) | 9 (10.8) | 12 (10.3) |
| Not Hispanic or Latino | 30 (90.9) | 74 (89.2) | 104 (89.7) |
| Hemophilia type, n (%) | |||
| Hemophilia A | 26 (78.8) | 65 (78.3) | 91 (78.5) |
| Hemophilia B | 7 (21.2) | 18 (21.7) | 25 (21.5) |
| Geographical region, n (%) | |||
| Asia | 21 (63.6) | 30 (36.1) | 51 (44) |
| Europe | 7 (21.2) | 32 (38.6) | 39 (33.6) |
| Middle East | 2 (6.1) | 10 (12) | 12 (10.3) |
| North America (Canada, Mexico, United States) | 3 (9.1) | 11 (13.3) | 14 (12.1) |
Source: Adapted from FDA Review
What are the benefits of this drug?
Patients who received factor on-demand had more bleeds requiring treatment (estimated per year) compared to when they were receiving HYMPAVZI (estimated per year).
Patients who received factor prophylaxis had approximately the same number of bleeds requiring treatment (estimated per year) compared to when they were receiving HYMPAVZI (estimated per year).
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2 and Table 3 summarize efficacy results for the group of patients who received factor on-demand during the observation period and for the group of patients who received factor prophylaxis during the observation period. The primary measure for efficacy was annualized bleeding rate. This was evaluated separately for bleeding events that required treatment (treated bleeds), bleeding events that occurred without trauma and required treatment (spontaneous bleeds, treated), bleeding events occurring in a joint that required treatment (joint bleeds, treated), all bleeding events whether or not treatment was required (total bleeds, treated and untreated), and bleeding events in target joints that required treatment (target joints, treated).
Table 2. Efficacy Results Comparing HYMPAVZI Prophylaxis With Factor On-Demand in Patients ≥12 Years of Age Without Factor VIII or Factor IX Inhibitors, BASIS
| Endpoints | Factor On-Demand During Observation Period N=33 | HYMPAVZI Prophylaxis During Treatment Period N=33 |
|---|---|---|
| Treated bleeds | ||
| ABR, model-based (95% CI) | 38.00 (31.03, 46.54) | 3.18 (2.09, 4.85) |
| Ratio vs. on-demand (95% CI) | 0.084 (0.059, 0.119) | |
| p-value | <0.0001 | |
| Spontaneous bleeds, treated | ||
| ABR, model-based (95% CI) | 30.93 (24.12, 39.67) | 2.44 (1.61, 3.69) |
| Ratio vs. on-demand (95% CI) | 0.079 (0.054, 0.114) | |
| p-value | <0.0001 | |
| Joint bleeds, treated | ||
| ABR, model-based (95% CI) | 32.86 (26.15, 41.29) | 2.83 (1.81, 4.44) |
| Ratio vs. on-demand (95% CI) | 0.086 (0.059, 0.125) | |
| p-value | <0.0001 | |
| Total bleeds, treated & untreated | ||
| ABR, model-based (95% CI) | 47.76 (39.60, 57.60) | 7.39 (5.08, 10.74) |
| Ratio vs. on-demand (95% CI) | 0.155 (0.116, 0.207) | |
| p-value | <0.0001 | |
| Target joint bleeds, treated | ||
| ABR, model-based (95% CI) | 23.18 (17.20, 31.24) | 1.84 (1.06, 3.17) |
| Ratio vs. on-demand (95% CI) | 0.079 (0.051, 0.124) | |
| p-value | <0.0001 | |
Source: Adapted from HYMPAVZI Prescribing Information.
p-value for the null hypothesis that the ratio = 0.5.
The estimated mean, ratio, and CIs for the ABR come from a negative binomial regression model.
Bleed definitions adapted based on ISTH criteria: Treated bleeds = bleeds treated with factor VIII or factor IX; Total bleeds = bleeds treated and not treated with factor VIII or factor IX.
Abbreviations: ABR, annualized bleeding rate; CI, confidence interval; ISTH, International Society on Thrombosis and Haemostasis
Table 3. Efficacy Results Comparing HYMPAVZI Prophylaxis With Factor Prophylaxis in Patients ≥12 Years of Age Without Factor VIII or Factor IX Inhibitors, BASIS
| Endpoints | Factor Prophylaxis During Observation Period N=83 | HYMPAVZI Prophylaxis During Treatment Period N=83 |
|---|---|---|
| Treated bleeds | ||
| ABR, model-based (95% CI) | 7.85 (5.09, 10.61) | 5.08 (3.40, 6.77) |
| Difference vs. RP (95% CI) | -2.77 (-5.37, -0.16) | |
| Spontaneous bleeds, treated | ||
| ABR, model-based (95% CI) | 5.86 (3.54, 8.19) | 3.78 (2.25, 5.31) |
| Difference vs. RP (95% CI) | -2.09 (-4.23, 0.06) | |
| Joint bleeds, treated | ||
| ABR, model-based (95% CI) | 5.66 (3.33, 7.98) | 4.13 (2.59, 5.67) |
| Difference vs. RP (95% CI) | -1.53 (-3.70, 0.64) | |
| Total bleeds, treated & untreated | ||
| ABR, model-based (95% CI) | 8.84 (5.97, 11.72) | 5.97 (4.13, 7.81) |
| Difference vs. RP (95% CI) | -2.87 (-5.61, -0.12) | |
| Target joint bleeds, treated | ||
| ABR, model-based (95% CI) | 3.36 (1.59, 5.14) | 2.51 (1.25, 3.76) |
| Difference vs. RP (95% CI) | -0.86 (-2.41, 0.70) | |
Source: Adapted from HYMPAVZI Prescribing Information.
The protocol specified non-inferiority criterion (upper bound of the 95% CI for the difference) was 2.5 for treated bleeds, spontaneous bleeds, joint bleeds; 1.2 for target joint bleeds; 2.9 for total bleeds.
The estimated mean, difference, and CIs for the ABR come from negative binomial regression model.
Bleed definitions adapted based on ISTH criteria: Treated bleeds = bleeds treated with factor VIII or factor IX; Total bleeds = bleeds treated and not treated with factor VIII or factor IX.
Abbreviations: ABR, annualized bleeding rate; CI, confidence interval; ISTH, International Society on Thrombosis and Haemostasis; RP, routine prophylaxis
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: All patients were males; therefore, differences in response among sexes could not be determined.
- Race: The majority of patients were Asian or White. The number of patients in other races was limited; therefore, differences in response among races could not be determined.
- Age: HYMPAVZI worked similarly in all tested age groups.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 4 and Table 5 present efficacy results by age, race, ethnicity, and hemophilia type for cohort OP-OD and OP-PPX, respectively. Analysis by sex was not performed because all patients were male. Due to the small sample size, these exploratory analyses should be interpreted with caution.
Table 4. Subgroup Analyses for the Primary Endpoint of Annualized Bleed Rate for Treated Bleeds by Subgroup for Observation Factor On-Demand Group, BASIS
| Subgroup | n | Factor On-Demand During Observation Period N=33 ABR (95% CI) | HYMPAVZI Prophylaxis During Treatment Period N=33 ABR (95% CI) | ABR Ratio (95% CI) |
|---|---|---|---|---|
| Age, years | ||||
| 12 to <18 | 2 | NE | NE | NE |
| 18 to <35 | 18 | 40.12 (30.85, 52.18) | 2.45 (1.43, 4.19) | 0.06 (0.04, 0.09) |
| ≥35 | 13 | 35.57 (24.75, 51.12) | 4.47 (2.45, 8.17) | 0.13 (0.07, 0.21) |
| Race | ||||
| White | 11 | 28.21 (18.35, 43.37) | 3.59 (1.61, 8.04) | 0.13 (0.07, 0.24) |
| Asian | 22 | 42.78 (34.55, 52.98) | 2.96 (1.87, 4.69) | 0.07 (0.05, 0.10) |
| Ethnicity | ||||
| Hispanic or Latino | 3 | NE | NE | NE |
| Not Hispanic or Latino | 30 | 39.17 (31.73, 48.35) | 3.36 (2.18, 5.17) | 0.09 (0.06, 0.12) |
| Hemophilia type | ||||
| Hemophilia A | 26 | 40.6 (32.36, 50.94) | 3.63 (2.36, 5.59) | 0.09 (0.06, 0.13) |
| Hemophilia B | 7 | 23.49 (19.27, 28.63) | 0.86 (0.26, 2.8) | 0.04 (0.01, 0.11) |
Source: Adapted from FDA Review
Abbreviations: ABR, annualized bleeding rate; CI, confidence interval; NE, not estimated due to small sample size
Table 5. Subgroup Analyses for the Primary Endpoint of Annualized Bleed Rate for Treated Bleeds by Subgroup for Observation Factor Prophylaxis Group, BASIS
| Subgroup | n | Factor On-Demand During Observation Period N=83 ABR (95% CI) | HYMPAVZI Prophylaxis During Treatment Period N=83 ABR (95% CI) | ABR Difference (95% CI) |
|---|---|---|---|---|
| Age, years | ||||
| 12 to <18 | 17 | 3.3 (0.73, 5.86) | 2.96 (0.39, 5.52) | -0.34 (-3.23, 2.55) |
| 18 to <35 | 29 | 6.31 (3.01, 9.62) | 4.45 (1.66, 7.24) | -1.86 (-4.82, 1.10) |
| ≥35 | 37 | 11.15 (5.88, 16.43) | 6.55 (3.78, 9.32) | -4.6 (-9.74, 0.54) |
| Race | ||||
| White | 45 | 6.17 (3.03, 9.31) | 4.02 (2.1, 5.94) | -2.15 (-4.78, 0.48) |
| Asian | 36 | 10.26 (5.37, 15.14) | 6.5 (3.49, 9.51) | -3.75 (-8.77, 1.26) |
| Black or African American | 1 | NE | NE | NE |
| Not reported | 1 | NE | NE | NE |
| Ethnicity | ||||
| Hispanic or Latino | 9 | 2.28 (0.02, 4.53) | 1.58 (0.37, 2.8) | -0.69 (-3.66, 2.28) |
| Not Hispanic or Latino | 74 | 8.53 (5.48, 11.57) | 5.52 (3.65, 7.39) | -3.01 (-5.91, -0.11) |
| Hemophilia type | ||||
| Hemophilia A | 65 | 9.12 (5.69, 12.56) | 5.21 (3.19, 7.23) | -3.91 (-7.10, -0.73) |
| Hemophilia B | 18 | 3.26 (1.77, 4.74) | 4.6 (1.91, 7.3) | 1.35 (-1.44, 4.13) |
Source: Adapted from FDA Review
Abbreviations: ABR, annualized bleeding rate; CI, confidence interval; NE, not estimated due to small sample size
What are the possible side effects?
The safety of HYMPAVZI was evaluated in adolescent and adult patients with severe hemophilia A or B without inhibitors (coagulation factor activity <1%) enrolled in the BASIS study. Patients (N=116) received HYMPAVZI prophylaxis 300 mg loading dose followed by 150 mg every week starting at Day 8 administered subcutaneously. Among patients receiving HYMPAVZI, 97% were exposed for 6 months or longer and 75% were exposed for at least one year.
Based on similar drugs and the way HYMPAVZI works, HYMPAVZI may increase the risk of thromboembolic complications. A serious side effect of peripheral swelling reported in one patient.
The most common adverse reactions (≥3% of participants) are injection site reaction, headache, and pruritus.
What are the possible side effects (results of trials used to assess safety)?
The side effects occurring in ≥3% of patients in the BASIS study where HYMPAVZI was used are shown in Table 6.
Table 6. Safety Results, Adverse Reactions Reported in ≥3% of Patients Treated With HYMPAVZI
| Adverse Reaction | All Patients N=116 n (%) |
|---|---|
| Injection site reaction | 11 (9) |
| Headache | 8 (7) |
| Pruritus | 4 (3) |
Source: Adapted from FDA Review
Were there any differences in side effects among sex, race, and age?
- Sex: All participants were male; therefore, differences in side effects between sexes could not be determined.
- Race: The majority of participant were Asian (50%) and White (48%). The occurrence of side effects was similar between White and Asian. The number of participants in other races was limited; therefore, differences in side effects among races could not be determined.
- Age: The occurrence of side effects was similar in patients younger and older than 18 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 7. Frequency of Adverse Events by Subgroup, Active Treatment Phase, Primary Safety Population, BASIS
| Characteristic | HYMPAVZI N=116 n/Ns (%) |
|---|---|
| Sex | |
| Male | 74/116 (63.8) |
| Age group, years | |
| <18 | 13/19 (68.4) |
| 18 to 44 | 39/70 (55.7) |
| 45 to 64 | 21/26 (80.8) |
| 65 to 74 | 1/1 (100) |
| Age group ≥65, years | |
| ≥65 | 1/1 (100) |
| Age group ≥75, years | |
| ≥75 | 0/116 (0) |
| Race | |
| Asian | 35/58 (60.3) |
| Black or African American | 0/1 (0) |
| White | 38/56 (67.9) |
| Missing | 1/1 (100) |
| Ethnicity | |
| Hispanic or Latino | 6/12 (50) |
| Not Hispanic or Latino | 68/104 (65.4) |
| Country | |
| United States | 1/1 (100) |
| Non-United States | 73/115 (63.5) |
| Hemophilia type | |
| Hemophilia A | 57/91 (62.6) |
| Hemophilia B | 17/25 (68) |
Source: Adapted from FDA Review
Primary Safety Population defined as all subjects who received at least one dose of HYMPAVZI during the 12-month treatment phase.
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.