View the results of the HAVEN 1-HAVEN 4 trials, which provided the primary analysis data supporting the approval of HEMLIBRA.
These studies don't prove that HEMLIBRA prevents bleeds during all types of physical activity. Everyone’s experience is different – talk to your doctor about what’s right for you.
TSUBASA Study: Describing Physical Activity and Bleed Events for People With Hemophilia A on HEMLIBRA
What did the study look at?
TSUBASA was an observational study evaluating the association between physical activity and bleeding in people with hemophilia A without factor VIII inhibitors receiving HEMLIBRA. An observational study describes real-world experiences without changing care and is not designed to show definitive benefit.
These data are a descriptive analysis and therefore should be interpreted with caution.
Who was part of the study?
- 129 participants without factor VIII inhibitors from 50 institutions in Japan enrolled and 73 people ≥ 6 years recorded ≥ 1 physical activity event*
- Median age was 39 years
- 82% had severe hemophilia A
- 13 had target joints at start of study
How were results tracked?
- Physical activity and any bleeds were tracked by participants over 5 different 8-day periods, using an app to record what activities they did and if any bleeding happened
How was HEMLIBRA given and for how long?
- HEMLIBRA was given according to prescription instructions
- People were observed for 97 weeks unless the study doctor or person decided to stop
- Everyone had prior exposure to coagulation factor products. There were 9 prophylactic uses of factor VIII within 24 hours prior to exercise in 6 people†
These results show what happened in the study, but they weren’t tested to rule out chance.
*In total, 129 people without factor VIII inhibitors enrolled in the study and received HEMLIBRA across 50 institutions in Japan. Physical activity data were collected from participants aged ≥6 years. Out of the 129 people who took part in the study, 104 met this age requirement.
†100 people (78%) received 1,403 doses of non-HEMLIBRA hemostatic agents; during exercise assessments, 30 (23%) received 77 doses.
Physical activity and bleeding events reported in TSUBASA
- 2 exercise events were linked to a bleed, both in people with severe hemophilia A
- Basketball (moderate risk)
- Fishing (low risk)
- The participants had no reported bleeding events in 24 weeks prior to the study and no target joints
- 968 exercise events were carried out by 73 participants, including:
- 58 high-risk activities
- 182 moderate risk activities
- 556 low-risk activities
- The average number of bleeds that needed additional treatment per year: 1.9
Physical activities were categorized by risk level according to National Bleeding Disorders Foundation (NBDF) guidelines.
Physical Activity Reported by 73 Participants ≥6 Years of Age
| NBDF Risk Level n=number of participants |
Number of physical activity events |
| Low (n=58) | 556 |
| Walking | 374 |
| Stretching to music | 84 |
| Weight training | 34 |
| Fishing | 27 |
| Golf | 18 |
| Swimming | 7 |
| Darts | 5 |
| Aqua dance | 3 |
| Trekking (climbing) | 3 |
| Hiking | 1 |
| Moderate (n=27) | 182 |
| Cycling/biking | 112 |
| Jogging/running | 20 |
| Tennis | 16 |
| Basketball | 10 |
| Dodgeball | 7 |
| Rubber-ball baseball | 4 |
| Table tennis | 4 |
| Jumping rope | 3 |
| Softball | 3 |
| Bowling | 2 |
| Soft tennis | 1 |
| High (n=14) | 58 |
| Soccer | 13 |
| Athletics/marathon | 9 |
| Trampoline | 8 |
| Weight lifting | 6 |
| Badminton | 5 |
| Karate | 4 |
| Volleyball | 4 |
| Motorcycle sports | 3 |
| Handball | 2 |
| Kendo | 2 |
| Football | 1 |
| Judo | 1 |
TSUBASA safety profile
- No new safety concerns were identified
- No side effects led to people switching off HEMLIBRA
- No HEMLIBRA-related serious side effects
- No people developed factor VIII inhibitors
| HEMLIBRA (N=129) |
|
| Total number of side effects | 137 |
| Patients with ≥1 side effect | 62 (48%) |
| Side effects leading to withdrawal from HEMLIBRA | 0 (0%) |
| Side effects related to HEMLIBRA | 7 (5%)‡ |
| People with ≥1 serious side effect | 13 (10%) |
| Side effects of special interest Blood clots |
0 (0%) |
‡7 people reported 10 side effects related on HEMLIBRA; 2 injection-site erythema and 5 injection-site reactions in 6 people. Headache, vertigo, and alopecia all occurred in 1 person.
Limitations
The study had no comparison group (everyone received HEMLIBRA) so these results cannot show how people would have done without HEMLIBRA.
Results are limited to people observed in the study and may not be applicable to individuals with different characteristics. Results are dependent on what people recorded in the app and how they interpreted their experiences.
There is potential for underestimation of activity-related bleeds due to any additional physical activity performed beyond 5 studied time periods.
BEYOND ABR: Joint Health and Physical Activity in People Switching From Factor VIII to HEMLIBRA
What the study looked at
BEYOND ABR (annualized bleed rate) is an ongoing 3-year Phase IV study evaluating joint health and physical activity in people with hemophilia A without factor VIII inhibitors who switched from factor VIII prophylaxis to HEMLIBRA.
The results shown here are from an interim analysis conducted after one year of the study. The study is still ongoing, so the final results may be different.
These data are a descriptive analysis and therefore should be interpreted with caution.
What did the study track?
- Joint health* as measured by:
- HJHS, a common joint health assessment tool used for people with hemophilia
- Numerical changes in problem joints†
- Number of target joints that had <3 bleeds in a year
- Physical activity data
- Number of people with zero treated bleeds
- Safety through number of and seriousness of side effects
Who was part of the study and for how long?‡
- 136 people with moderate to severe hemophilia A average age of 29 years
- Age range was 13-63 years
- 24% had at least 1 joint with previous surgery or procedure
- 82% had severe hemophilia A
- The rest had moderate hemophilia A
- The median treatment duration with HEMLIBRA was 76 weeks. HEMLIBRA was dosed according to label
- Range of 13-122 weeks
These results are from the first year of HEMLIBRA treatment in this study.
These results show what happened in the study, but they weren’t tested to rule out chance.
*People or single joints with a medical history of joint surgery/procedure were not included in the HJHS (hemophilia joint health score) analysis.
†Defined as long-lasting joint pain (in neck, shoulders, elbows, wrists, knees, hips, ankles, spine) or trouble moving joints, with or without ongoing bleeding.
‡Eligible participants had received prophylaxis factor VIII treatment for at least 24 weeks before joining the study. People who had a joint replacement or other joint procedure within the past 2 years were not included.
Joint health results
Joint health was measured before starting HEMLIBRA and again at 6 and 12 months using HJHS (hemophilia joint health score), a common joint health assessment tool used for people with hemophilia A.
Meaningful changes in HJHS were ≥4 points at the participant level.
Average joint health scores decreased from 10 to 8 after 1 year on HEMLIBRA
The average joint health score decreased by 2.0 points from baseline after 6 months of HEMLIBRA treatment (93 people) and by 2.8 points after 1 year (88 people).
Changes in individual joint health scores from the start of the study
Change defined as ≥4-point increase or decrease in joint health score. <4-point increase or decrease defined as no change.
In 88 people after 1 year on HEMLIBRA:
- 26% had a decrease in joint health scores
- 68% had no change in joint health scores
- 6% had an increase in joint health scores
Changes in reported problem joints from the start of the study
In people who remained in the study for at least 1 year, all baseline target joints were resolved (27/27) in 15 people, meaning the target joint experienced fewer than 3 spontaneous or traumatic bleeds over a 1-year period.
Change defined as ≥1-point increase or decrease in participant-reported problem joints.
In 117 people after 1 year on HEMLIBRA:
- 30% of people had decreased the number of problem joints
- 56% of people had no change in the number of problem joints
- 14% of people had increased the number of problem joints
Physical activity results
Physical activity was measured using the International Physical Activity Questionnaire (IPAQ), a survey that looks at how active people are in daily life.
From the start of the study after 1 year on HEMLIBRA, the proportion of participants reporting:
- High activity levels increased 6 percentage points
- Moderate activity levels increased 3 percentage points
- Low activity levels decreased 10 percentage points
Overall Physical Activity Levels Measured by iPAQ Scores
‖The same individuals are included in both the baseline and Month 12 groups. This graph shows how the percentage of people doing low, moderate, or high levels of physical activity changed over time.
Other results while taking HEMLIBRA
- 81% (110/136) of people had zero treated bleeds between Weeks 1 to 24
- 78% (105/134) of people had zero treated bleeds between Weeks 25 to 48
- 96% (125/130) of people preferred HEMLIBRA to their previous factor VIII prophylaxis at 6 months
- 0.8% (1/130) preferred their previous treatment
- 3% (4/130) had no preference
Safety results
- No new safety concerns were identified
- No side effects leading to treatment discontinuation
- No HEMLIBRA-related serious side effects
- There were no blood clots or thrombotic microangiopathies (TMAs)
| HEMLIBRA (N=136) |
|
| Total number of side effects, n | 372 |
| Total number of patients with ≥1 side effects, n (%) | 113 (83%) |
| Serious side effects§ | 9 (7%) |
| Side effect leading to dose modification | 2 (2%) |
| HEMLIBRA-related side effects | 18 (13%) |
| Side effects of special interest, n (%)‖ Blood clots |
0 (0) |
§Included flu, vomiting blood, blood in the stool, ligament rupture, joint bleeding, chest pain, seizures, upper respiratory infection, multiple trauma, none were deemed related to treatment.
‖Included anaphylactic reaction, thromboembolic events, TMAs, drug induced liver injuries.