Page 20 - Roche Hemlibra Non-inhibitors - Product Monograph

7.2. EFFICACY OF HEMLIBRA ®

HAVEN 3 (Mahlangu J et al. 2018)
The HAVEN clinical trial programme by Roche is one of the largest pivotal clinical trial

programmes in hemophilia. It is designed to assess the efficacy and safety of HEMLIBRA in
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people with and without FVIII inhibitors. The programme also assesses the potential of
HEMLIBRA to help overcome current clinical challenges:
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• the short-lasting effects of existing treatments

• the development of FVIII inhibitors
• the need for frequent venous access (Roche release. 2019)

Study design

Arm A: emicizumab
n = 36 1.5 mg/kg QW maintenance
(NIS r = 10)
Pre-study R † Arm B: emicizumab
episodic* FVIII 2:2:1 n = 35 3 mg/kg Q2W maintenance
(NIS n = 10)
Screening 24-week primary efficazy analysis Emicizumab continuation
Severe
haemophiliamA without n = 18 Arm C: no prophylaxis
FVIII inhibitors (NIS n = 5)

Pre-study Arm D: emicizumab
FVIII n = 63 1.5 mg/kg QW maintenance
prophylaxis (NIS n = 48)

* 24-week bleed rate 5 for participants receiving episodic FVIII
† Randomisation stratified based on 6-month bleed rate of <9 or 9
F, factor; NIS, non-interventional study; QW, once weekly; Q2W, every 2 weeks; R, randomised

Primary efficacy outcomes

Arm A Arm B Arm C
emicizumab QW emicizumab Q2W no prophylaxis
prophylaxis n = 36 prophylaxis n = 35 n = 18

Duration of efficacy period, 29.6 (17.3–49.6) 31.3 (7.3–50.6) 31.3 (7.3–50.6)
weeks Median (min–max)
Treated bleeds (with FVIII)
ABR, model based* (95% CI) 1.5 (0.9–2.5) 1.5 (0.9–2.5) 1.5 (0.9–2.5)

% risk reduction† 96% 97%
RR, p-value 0.04, p<0.0001 0.03, p<0.0001

Median ABR, calculated (IQR) 0.0 (0.0–2.5) 0.0 (0.0–1.9) 40.4 (25.3–56.7)
Participants with zero 55.6 (38.1–72.1) 60.0 (42.1–76.1) 0 (0.0–18.5)
bleeds, % (95% CI)

Participants with 91.7 (77.5–98.2) 94.3 (80.8–99.3) 0 (0.0–18.5)
0–3 bleeds, % (95% CI)

* Data from 48 participants in Arm D who participated in the non-interventional study
† The ABR was calculated with the use of a negative binomial-regression model
ABR, annualised bleed rate; CI, confidence interval; IQR, interquartile range; NIS, non-interventional study; QW, once weekly; RR, rate ratio

HEMLIBRA Monograph-Non-inhibitors | 18
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