|Roche(SIX: RO, ROG; OTCQX: RHHBY) today announced full results from the phase IIIHAVEN 3 study evaluating Hemlibra® (emicizumab) prophylaxis administered everyweek or every two weeks in people with haemophilia A without factor VIIIinhibitors and the phase III HAVEN 4 study evaluating Hemlibra prophylaxisadministered every four weeks in people with haemophilia A with or withoutfactor VIII inhibitors. Data from both pivotal studies were presented today aslate-breaking abstracts at the World Federation of Hemophilia (WFH) 2018 WorldCongress in Glasgow, Scotland.
“Hemlibrais the first medicine to show superior efficacy to prior factor VIIIprophylaxis, the current standard of care therapy, as demonstrated by astatistically significant reduction in treated bleeds in the HAVEN 3 studyintra-patient comparison,” said Johnny Mahlangu, Faculty of Health Sciences,University of the Witwatersrand and NHLS, Johannesburg, South Africa. “Evenwith current prophylactic treatments, many people with haemophilia A continueto have bleeds that can lead to long-term joint damage, and there is a need formore treatment options.”
In the phase IIIHAVEN 3 study, adults and adolescents aged 12 years or older without factorVIII inhibitors who received Hemlibra prophylaxis every week or every two weeksshowed a 96% (p<0.0001) and 97% (p<0.0001) reduction in treated bleeds,respectively, compared to those who received no prophylaxis. In addition, 55.6%(95% CI: 38.1; 72.1) of people treated with Hemlibra every week and 60% (95%CI: 42.1; 76.1) of people treated with Hemlibra every two weeks experiencedzero treated bleeds, compared to 0% (95% CI: 0.0; 18.5) of people treated withno prophylaxis. Importantly, in an intra-patient comparison, in patients whowere previously enrolled in a prospective non-interventional study (NIS),once-weekly Hemlibra prophylaxis showed superior efficacy compared to priorfactor VIII prophylaxis, the standard of care for people with haemophilia Awithout factor VIII inhibitors, as demonstrated by a 68% reduction(p<0.0001) in treated bleeds. Additionally, 93.7% (n=89/95; 95% CI, 86.8;97.7) of all participants who completed a treatment preference survey preferredHemlibra to their previous haemophilia treatment, with 97.8% (n=45/46) of thosein the intra-patient comparison preferring Hemlibra to their prior factor VIIIprophylaxis. There were no unexpected or serious adverse events (AEs) relatedto Hemlibra, and the most common AEs were consistent with previous studies. Themost common AEs occurring in 5% or more of people in the HAVEN 3 study wereinjection site reactions, joint pain (arthralgia), common cold symptoms(nasopharyngitis), headache, upper respiratory tract infection and influenza.
“These new pivotaldata show that Hemlibra controlled bleeds in people with haemophilia A, whileoffering the flexibility of less frequent subcutaneous dosing options,” saidSandra Horning, MD, Roche’s Chief Medical Officer and Head of Global ProductDevelopment. “With this data, we now have positive results from all four of ourphase III trials that reinforce the overall efficacy and safety of Hemlibra andits potential to improve care for all people with haemophilia A.”
In the single-armphase III HAVEN 4 study, adults and adolescents aged 12 years or older with orwithout factor VIII inhibitors receiving Hemlibra prophylaxis every four weekshad a median annualised bleeding rate for treated bleeds of 0.0 (IQR: 0.0; 2.1),with 56.1% (95% CI: 39.7; 71.5) of people experiencing zero treated bleeds and90.2% (95% CI: 76.9; 97.3) experiencing three or fewer treated bleeds. Theseresults demonstrate that Hemlibra administration every four weeks can provideclinically meaningful control of bleeding in people with haemophilia A with orwithout factor VIII inhibitors. Additionally, all participants (n=41/41; 95%CI, 91.4; 100.0) who responded to a patient preference survey preferredHemlibra to their previous haemophilia treatment. There were no serious AEsrelated to Hemlibra, and the most common AEs were consistent with previousstudies. Injection site reaction was the most common AE, occurring in ninepeople in the HAVEN 4 study.
Separately,real-world data from the NIS on the impact of haemophilia A on health-relatedquality of life (HRQoL) and the burden of current treatment (either on-demandor prophylactic bypassing agents or factor VIII replacement therapy, dependingon inhibitor status and local clinical guidelines) were also presented. Resultsfrom a cohort of the NIS in children with haemophilia A with factor VIIIinhibitors showed that living with and managing the condition has asubstantially negative impact on physical and emotional health and results in asignificant burden for caregivers. In another cohort of the NIS, adults andadolescents with haemophilia A without factor VIII inhibitors reported higherHRQoL with prophylactic factor VIII treatment compared to episodic factor VIIItreatment, based on validated tools including Haem-A-QoL and Haemo-QoL-SF. Inaddition, prophylactic factor VIII therapy resulted in fewer school and workdays missed compared to episodic treatment. This NIS represents one of thelargest studies of this type in people with haemophilia A with or withoutfactor VIII inhibitors, and collected prospective real-world data for use as avalid historical control for pivotal studies in patients with haemophilia A.
In April 2018, the USFood and Drug Administration (FDA) granted Breakthrough Therapy Designation toHemlibra for people with haemophilia A without factor VIII inhibitors, based ondata from the HAVEN 3 study. Hemlibra was approved by the FDA in November 2017for routine prophylaxis to prevent or reduce the frequency of bleeding episodesin adults and children with haemophilia A with factor VIII inhibitors based onresults from the HAVEN 1 study and interim results from the HAVEN 2 study.Hemlibra was also recently approved by regulatory authorities in othercountries around the world, including by the European Commission in February2018 for routine prophylaxis of bleeding episodes in people with haemophilia Awith factor VIII inhibitors. Data from both the HAVEN 3 and HAVEN 4 studies arebeing submitted to health authorities around the world for approvalconsideration.
About HAVEN 3 (NCT02847637)
HAVEN 3 is arandomised, multicentre, open-label, phase III study evaluating the efficacy,safety and pharmacokinetics of Hemlibra prophylaxis versus no prophylaxis(episodic/on-demand factor VIII treatment) in people with haemophilia A withoutfactor VIII inhibitors. The study included 152 patients with haemophilia A (12years of age or older) who were previously treated with factor VIII therapyeither on-demand or for prophylaxis. Patients previously treated with on-demandfactor VIII were randomised in a 2:2:1 fashion to receive subcutaneous Hemlibraprophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the endof study (Arm A), subcutaneous Hemlibra prophylaxis at 3 mg/kg/wk for 4 weeks,followed by 3 mg/kg/2wks for at least 24 weeks (Arm B), or no prophylaxis (ArmC). Patients previously treated with factor VIII prophylaxis receivedsubcutaneous Hemlibra prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5mg/kg/wk until the end of study (Arm D). Episodic treatment of breakthroughbleeds with factor VIII therapy was allowed per protocol.
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