Drug Trials Snapshot: ALHEMO
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 ALHEMO 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).
ALHEMO (concizumab)
al-HEE-mo
Novo Nordisk Inc
Original Approval date: December 20, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ALHEMO is a tissue factor pathway inhibitor (TFPI) antagonist that is used to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with:
- Hemophilia A (congenital factor VIII deficiency) with FVIII inhibitors
- Hemophilia B (congenital factor IX deficiency) with FIX inhibitors
How is this drug used?
ALHEMO is administered by subcutaneous injection to the abdomen or thigh with daily rotation of injection sites.
Who participated in the clinical trials?
The FDA approved ALHEMO based on evidence from one clinical trial of 133 patients with hemophilia A with inhibitors (HAwI) and hemophilia B with inhibitors (HBwI). The trial was conducted at 69 sites in a total of 26 countries in North America, Europe, Africa, Asia, and Oceania of which the majority (95%, 126 patients) were from outside the United States. The same trial was used to evaluate the safety of the drug.
How were the trials designed?
ALHEMO was evaluated in 133 patients with HAwI and HBwI. The Explorer7 trial (NCT04083781), was a multi-national, multi-center, open-label, phase 3 trial that investigated the safety and efficacy of ALHEMO for routine prophylaxis in 91 adults (58 patients with HAwI and 33 patients with HBwI) and 42 adolescents (22 patients with HAwI and 20 patients with HBwI). All participants were patients who have been prescribed, or are in need of, treatment with bypassing agents.
The trial was comprised of four arms, two randomized arms and two non-randomized arms:
- Arms 1 and 2 included 52 patients (27 HAwI and 25 HBwI), previously treated on-demand, who were randomized 1:2 to no prophylaxis (Arm 1: on-demand treatment with bypassing agents) or ALHEMO prophylaxis (Arm 2), with stratification by hemophilia type (HAwI or HBwI) and prior 24-week bleeding rate (<9 or ≥9).
- Arms 3 and 4 consisted of 81 additional patients (53 HAwI and 28 HBwI) treated with ALHEMO prophylaxis.
Treatment with ALHEMO included a loading dose of 1 mg/kg on the first day and a once-daily dose of 0.20 mg/kg starting on the second day. The dose was individualized to 0.25 mg/kg or 0.15 mg/kg if ALHEMO plasma concentration (measured once after four weeks of treatment) was <200 ng/mL or >4000 ng/mL, respectively. Measurement of ALHEMO plasma concentration after four weeks was used to optimize the daily maintenance dose.
The benefit of ALHEMO was assessed by comparing the number of bleeding episodes that required treatment when receiving ALHEMO prophylaxis (Arm 2) compared to the number of bleeding episodes that required treatment when receiving factor on-demand therapy (Arm 1).
DEMOGRAPHICS SNAPSHOT
Baseline Demographics by Sex
All patients enrolled were male.
Figure 1 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of ALHEMO.
Figure 1. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of ALHEMO.
Figure 2. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by ethnicity were enrolled in the clinical trial used to evaluate the efficacy of ALHEMO.
Figure 3. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Safety Population
| ALHEMO PPX | ||||
|---|---|---|---|---|
| Characteristic | No PPX Arm 1 Main N=19 | Arm 2 Main N=33 | Arm 3 Overall N=21 | Arm 4 Overall N=60 |
| Sex, n (%) | ||||
| Male | 19 (100) | 33 (100) | 21 (100 | 60 (100) |
| Age, years | ||||
| Mean (SD) | 32.3 (17.6) | 24.9 (14.3) | 37.9 (12) | 27.6 (13.2) |
| Median (min, max) | 27 (15, 67) | 17 (12, 61) | 35 (20, 61) | 25.5 (12, 79) |
| Age group, years, n (%) | ||||
| ≥12 to <18 | 6 (31.6) | 18 (54.5) | 0 | 18 (30.0) |
| ≥18 to <65 | 12 (63.2) | 15 (45.5) | 21 (100) | 41 (68.3) |
| ≥65 to <85 | 1 (5.3) | 0 | 0 | 1 (1.7) |
| Age group ≥65, years, n (%) | ||||
| ≥65 | 1 (5.3) | 0 | 0 | 1 (1.7) |
| Age group ≥75, years, n (%) | ||||
| ≥75 | 0 | 0 | 0 | 1 (1.7) |
| Race, n (%) | ||||
| American Indian or Alaska Native | 1 (5.3) | 1 (3.0) | 0 | 1 (1.7) |
| Asian | 6 (31.6) | 14 (42.4) | 4 (19.0) | 13 (21.7) |
| Black or African American | 1 (5.3) | 4 (12.1) | 0 | 4 (6.7) |
| White | 9 (47.4) | 12 (36.4) | 17 (81.0) | 40 (66.7) |
| Not reported | 2 (10.5) | 2 (6.1) | 0 | 2 (3.3) |
| Ethnicity, n (%) | ||||
| Hispanic or Latino | 1 (5.3) | 3 (9.1) | 0 | 2 (3.3) |
| Not Hispanic or Latino | 16 (84.2) | 29 (87.9) | 21 (100) | 56 (93.3) |
| Not reported | 2 (10.5) | 1 (3.0) | 0 | 2 (3.3) |
| Region of participation, n (%) | ||||
| Africa | 1 (5.3) | 4 (12.1) | 0 | 11 (18.3) |
| Asia | 5 (26.3) | 14 (42.4) | 4 (19.0) | 17 (28.3) |
| Europe | 11 (57.9) | 10 (30.3) | 16 (76.2) | 26 (43.3) |
| North America | 2 (10.5) | 4 (12.1) | 1 (4.8) | 3 (5.0) |
| Oceania | 0 | 1 (3.0) | 0 | 3 (5.0) |
| Region group of participation, n (%) | ||||
| Outside the United States | 18 (94.7) | 30 (90.9) | 20 (95.2) | 58 (96.7) |
| United States | 1 (5.3) | 3 (9.1) | 1 (4.8) | 2 (3.3) |
Source: Adapted from FDA Review
Abbreviation: PPX, prophylaxis; SD, standard deviation
What are the benefits of this drug?
Patients who received ALHEMO prophylaxis had a significant reduction in bleeding (annualized bleeding rate) compared to patients who received on-demand therapy.
What are the benefits of this drug (results of trials used to assess efficacy)?
Efficacy was evaluated in HAwI and HBwI when all patients in the no prophylaxis (arm 1) and ALHEMO prophylaxis (arm 2) treatment arms had completed at least 24 or 32 weeks, respectively, by comparing the number of treated bleeding episodes between ALHEMO prophylaxis (arm 2) and no prophylaxis (arm 1).
Using a negative binomial model, a ratio of the annualized bleeding rates (ABR) was estimated to 0.14 (p<0.001), corresponding to a reduction in ABR of 86% for subjects on ALHEMO prophylaxis compared to no prophylaxis. The estimated mean ABR was 1.7 (95%CI: 1.01; 2.87) for patients on ALHEMO prophylaxis (arm 2) and 11.8 (95%CI: 7.03; 19.86) for patients on no prophylaxis (arm 1).
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: Because all participants were male, differences between sexes in how ALHEMO worked could not be determined.
- Race: ALHEMO worked similarly in White and Asian patients. The number of patients of other races was small; therefore, differences in how ALHEMO worked in other races could not be determined.
- Age: Because there was only one patient older than 65 years of age, differences between patients younger and older than 65 years of age in how ALHEMO worked could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 2. Efficacy Results by Subgroupa, Efficacy Population, Arm 1 (No PPX) and Arm 2 (ALHEMO PPX)
| Subgroup | Category | Arm | N | Mean ABR (SD) |
|---|---|---|---|---|
| Race | Asian | Arm 1 | 6 | 17.6 (28.1) |
| Arm 2 | 14 | 3.5 (4.4) | ||
| Black or African American | Arm 1 | 1 | 14.3 (NE) | |
| Arm 2 | 4 | 0.8 (1.6) | ||
| White | Arm 1 | 9 | 23.9 (27.4) | |
| Arm 2 | 12 | 6.1 (19) | ||
| Other | Arm 1 | 3 | 4.9 (4.3) | |
| Arm 2 | 3 | 0 (0) | ||
| Ethnicity | Hispanic or Latino | Arm 1 | 1 | 0 (NE) |
| Arm 2 | 3 | 0 (0) | ||
| Not Hispanic or Latino | Arm 1 | 16 | 20.9 (26.2) | |
| Arm 2 | 29 | 4.3 (12.4) | ||
| Not reported | Arm 1 | 2 | 7.3 (0.8) | |
| Arm 2 | 1 | 0 (NE) |
Source: Adapted from FDA Review
a Subgroup results for sex and age were not included because all patients were male and there was only one patient older than 65 years of age.
Abbreviations: ABR, annualized bleeding rate; PPX, prophylaxis; N, number of patients; NE, not estimable; SD, standard deviation
What are the possible side effects?
ALHEMO can cause thromboembolic events, hypersensitivity, and increased laboratory values of fibrin D dimer and prothrombin fragment 1+2. The most common side effects of ALHEMO include injection site reactions and urticaria.
What are the possible side effects (results of trials used to assess safety)?
Table 3. Safety Results, Safety Population
| Adverse Reaction | ALHEMO Prophylaxis N=33% | On-Demand Treatment N=19% |
|---|---|---|
| Injection site reaction | 18 | 0 |
| Urticaria | 6 | 0 |
Source: Adapted from ALHEMO Prescribing Information
Injection site reactions included: Injection site bruising, Injection site erythema, Injection site hematoma, Injection site hemorrhage, Injection site reaction, and Injection site urticaria.
Urticaria included: Urticaria and Injection site urticaria.
Were there any differences in side effects among sex, race, and age?
- Sex: All patients in the trial were male.
- Race: The occurrence of side effects was similar between races.
- Age: There were not sufficient numbers of patients enrolled age ≥65 years to draw conclusions regarding differences in safety based on age.
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.