Data from ongoing Phase 3 clinical trials show that Genentech’s Hemlibra (emicizumab-kxwh) prophylaxis — or preventive treatment — greatly outperforms current standard-of-care therapies, leading to significant reductions in the number of bleeds in hemophilia A patients regardless of inhibitor status.
Promising results from these pivotal studies may lead to Hemlibra treating more hemophilia A patients — with a choice of dosing regimes — should they be accepted by the FDA and other regulatory bodies, a company medical director said in an interview with Hemophilia News Today. (An upcoming article, based on the interview, will look more closely at this treatment and these trials).
The HAVEN 3 and HAVEN 4 updates were part of presentations made at the World Federation of Hemophilia (WFH) 2018 congress in Glasgow, Scotland, running through May 24.
Patients ages 12 and older are taking part in the trials: those without factor VIII inhibitors in HAVEN 3, and those with or without factor VIII inhibitors in HAVEN 4. Hemlibra is already approved in the U.S., Europe and elsewhere to treat hemophilia A patients with inhibitors.
HAVEN 3 (NCT02847637) recruited 152 patients previously treated with a factor VIII therapy, either on a as-needed or prophylaxis basis, and randomized them into three groups or study arms. Data covered at least 24 weeks of treatment.
Hemlibra prophylaxis was administered every week or every two weeks to patients in two arms; the third group served as controls and were given Hemlibra as needed (episodically) for bleeds. Results presented at WFH showed a 96% reduction in treated bleeds among those on weekly treatment (1.5 mg/kg) and a 97% reduction in those treated every two weeks (3 mg/kg), compared to patients in the control arm.
Moreover, 55.6% and 60% of patients given Hemlibra prophylaxis every week or two weeks, respectively, had no new bleeds requiring treatment — while all patients in the non-prophylactic group experienced new bleeds.
A survey also found that 93.7% of patients preferred Hemlibra to prior factor VIII treatments (89 respondents), and 97.8% of those in an intra-patient comparison of prior prophylaxis users favored Hemlibra (45 respondents).
Importantly, the study’s researchers said, that intra-patient comparison of prior factor VIII prophylaxis — the standard therapy for hemophilia A patients without factor VIII inhibitors — showed once-weekly Hemlibra to be more the effective treatment, with 68% fewer treated bleeds. (The comparison involved patients previously enrolled in a prospective non-interventional study.)
“HEMLIBRA is the first medicine to show superior efficacy to prior factor VIII prophylaxis … as demonstrated by a statistically significant reduction in treated bleeds in the HAVEN 3 study intra-patient comparison,” Johnny Mahlangu, with the faculty of health sciences at the University of the Witwatersrand and NHLS in Johannesburg, South Africa, said in a press release.
The therapy’s safety profile also remained consistent with that of previous trials, with the most common adverse effects — reactions at the injection site, joint pain (arthralgia), common cold symptoms (nasopharyngitis), headache, upper respiratory tract infection, and influenza — reported in at least 5% of HAVEN 3 patients.
In the single-arm HAVEN 4 (NCT03020160) study, 48 patients were treated with Hemlibra as prophylaxis at 6 mg/kg every four weeks. Data showed that 56.1% had zero bleeds, and 90.2% had three or fewer bleeds over at least 24 weeks.
In a survey answered by 41 of these patients, all preferred Hemlibra to previous therapies. Adverse effects were again consistent with previous findings, with the most common being injection site reactions.
“The ultimate goal for the development program, when we started, was to have Hemlibra approved for hemophilia A patients with and without inhibitors,” Gallia Levy, associate group medical director at Genentech, said in the interview from the conference site.
“The Haven 3 and 4 trials will hopefully support the expansion to hemophilia A patients without inhibitors,” Levy added.
Improving care is a key goal for hemophilia patients, as shown by a real-world study also presented at the conference. Children with factor VIII inhibitors reported that a marked detrimental impact on their quality of life, both physically and mentally.
Adults and adolescents without inhibitors also reported a higher quality of life when using prophylactic factor VIII treatments, resulting in fewer school and work days skipped compared to only episodic, or as-needed, VIII treatment.
“The beauty of that questionnaire is data in not easily misinterpreted, so that you get a very clear answer. But data — reasons why — are still being investigated, and will be published in the future,” Levy said.
Data from the Haven 3 study supported a U.S. Food and Drug Administration decision to grant Breakthrough Therapy Designation to Hemlibra for people with hemophilia A without factor VIII inhibitors in April.
Based on findings from two previous Phase 3 trials, Hemlibra was approved to treat bleeding episodes in hemophilia A patients with factor VIII inhibitors in the U.S. in November 2017, and throughout the European Union in March.