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Clinical Trials

Date: 2017-12-09

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at The American Society of Hematology (ASH) 2017

Company: Roche (Switzerland)

Product: emicizumab (ACE910 - anti-factor IXa x anti-factor X humanized bispecific antibody)

Action mechanism:

  • bispecific antibody. Emicizumab is a bispecific antibody that mimics coagulation factor VIII. It is currently investigated as a therapy for people with hemophilia A. Emicizumab was designated as a Breakthrough Therapy by the FDA in September 2015.

Disease: hemophilia A

Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases

Country: Costa Rica, Germany, Italy, Japan, South Africa, Spain, Turkey, UK, USA

Trial details:

  • HAVEN 2 is a single-arm study that will enroll children (less than 12 years of age) and adolescents (12 to 17 years of age) with hemophilia A and FVIII inhibitors who are currently receiving treatment with bypassing agents. Participants will receive weekly subcutaneous doses of emicizumab for a designated period of 52 weeks. All participants will continue to receive standard of care/background treatment with their usual episodic bypassing agent therapy to treat breakthrough bleeds as needed. (NCT02795767)
  • HAVEN 2 is the second phase III study in the emicizumab clinical development programme to report results.
  • Two additional phase III studies of emicizumab are ongoing:
  • HAVEN 3, evaluating emicizumab prophylaxis dosed once weekly or once every other week in people 12 years of age or older with haemophilia A without inhibitors to factor VIII.
  • HAVEN 4, evaluating emicizumab prophylaxis dosed every four weeks in people 12 years of age or older with haemophilia A with or without inhibitors to factor VIII.

Latest news:

  • • On December 9, 2017, Roche announced that new data from the ongoing Hemlibra® (emicizumab) clinical development programme were presented at the 59th American Society of Hematology (ASH) Annual Meeting. These data include longer-term results from the pivotal HAVEN 2 study in people with haemophilia A with inhibitors to factor VIII, showing once-weekly subcutaneous Hemlibra® prophylaxis demonstrated superior efficacy compared to prior treatment with bypassing agents (BPAs) as prophylaxis or on-demand. In updated results from the HAVEN 2 study with six additional months of data and 40 more children (younger than 12 years of age), 94.7% (95% CI: 85.4; 98.9) of children with haemophilia A with inhibitors who received Hemlibra® prophylaxis had zero treated bleeds (n=57). The intra-patient analysis comparing the effects of different therapies in the same child (n=13) showed a 99% reduction in treated bleeds with Hemlibra prophylaxis compared to prior treatment with a BPA, either as prophylaxis (n=12) or on-demand (n=1). Substantial improvements in health-related quality of life and aspects of caregiver burden, measured by the haemophilia-specific quality of life short form (Haemo-QoL-SF) and adapted health-related quality of life in haemophilia patients with inhibitors (Inhib-QoL) questionnaires, were also observed with Hemlibra® prophylaxis compared to prior BPA prophylaxis. These data were featured today in the official press programme of the ASH Annual Meeting. With nearly ten additional months of follow-up, updated results from the HAVEN 1 intra-patient analysis of adults and adolescents showed an 88% (risk rate [RR]=0.12, 95% CI: 0.05; 0.28) reduction in treated bleeds with Hemlibra® prophylaxis compared to prior BPA prophylaxis (n=24). The results also showed a 95% (RR=0.05, 95% CI: 0.02; 0.12) reduction in treated bleeds in patients who received Hemlibra® prophylaxis compared to prior on-demand BPA treatment (n=24). After more than one year, substantially more patients continued to experience zero bleeds with Hemlibra® prophylaxis compared to their prior prophylaxis or on-demand BPA treatment across bleed endpoints, including treated bleeds and all bleeds. The previously reported improvement in health status after 24 weeks, measured by the haemophilia-specific quality of life (Haem-A-QoL) and EuroQol 5-Dimensions 5-level (EQ-5D-5L) questionnaires, was also maintained with longer follow-up. Data from HAVEN 1 and HAVEN 2 are being reviewed under accelerated assessment by the European Medicines Agency (EMA) and submissions to health authorities around the world are ongoing.
  • • On November 2, 2017, Chugai Pharmaceutical announced that oral and poster presentations will be given with regard to emicizumab at The American Society of Hematology (ASH) 2017 in Atlanta, Georgia, United States. Data from additional six-month follow-up of global Phase lll studies in hemophilia A with inhibitors to factor VIII, HAVEN 1 study and HAVEN 2 study will be shown at the conference.
  • • On July 10, 2017,  Roche announced that interim analysis of the phase III HAVEN 2 study of emicizumab in children are being presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress. Interim results from the single arm HAVEN 2 study in children younger than 12 years of age with haemophilia A with inhibitors who received emicizumab prophylaxis are consistent with the positive results from the HAVEN 1 study. After a median observation time of 12 weeks, the study showed that only one of 19 children receiving emicizumab reported a treated bleed. There were no reported joint or muscle bleeds.
  • An intra-patient comparison (n=8) in a subset of these children who were previously enrolled in the NIS, showed that all experienced a 100% reduction in treated bleeds following treatment with emicizumab (previous annualised bleeding rate [ABR] ranged from 0 to 34.24); this group included seven children who had received prior BPA prophylaxis, and one who had received prior on-demand BPA. The data also indicate that the same dose of emicizumab is appropriate for children as for adults and adolescents, based on the levels of emicizumab in the blood (pharmacokinetics) of the children compared with the levels of emicizumab in the blood of adults and adolescents. The most common AEs with emicizumab in the HAVEN 2 study were mild injection site reactions and common cold symptoms (nasopharyngitis). No TE or TMA events were observed.
  • Data from both HAVEN 1 and HAVEN 2 have been submitted for approval consideration to the European Medicines Agency (EMA) and the FDA.
  • Summary of HAVEN2 study interim results:
  • • On June 26, 2017,  Chugai Pharmaceutical and Genentech announced results from the interim analysis of HAVEN 2 study. The data will be presented on July 10 at the upcoming 26th International Society on Thrombosis and Haemostasis (ISTH) Meeting in Berlin, Germany (July 8 to 13). The interim analysis was conducted with 19 children younger than 12 years of age with haemophilia A with inhibitors who require treatment with BPAs.  Interim results are consistent with the positive results from the HAVEN 1 study. After a median observation time of 12 weeks, the study showed that only one of 19 children receiving emicizumab reported a treated bleed. There were no reported joint or muscle bleeds. An intra-patient comparison (n=8) in patients who were previously enrolled in the NIS showed that all patients experienced a 100 percent reduction in treated bleeds following treatment with emicizumab (previous ABR ranged from 0 to 34.24); this included seven children who had received prior BPA prophylaxis and one who had received prior on-demand BPA. The data also indicate that the same dose of emicizumab is appropriate for children as for adults and adolescents, based on the levels of emicizumab in the blood (pharmacokinetics) of the children compared with the level of emicizumab in the blood of adults and adolescents. The most common AEs with emicizumab in the HAVEN 2 study were mild injection site reactions and common cold symptoms (nasopharyngitis).
  • • On April 17, 2017, Roche announced interim results from the phase III HAVEN 2 study evaluating emicizumab prophylaxis in children less than 12 years of age with haemophilia A and inhibitors to factor VIII. At this interim analysis after a median of 12 weeks of treatment, emicizumab prophylaxis showed a clinically meaningful reduction in the number of bleeds over time. These findings are consistent with results from the phase III HAVEN 1 study in adults and adolescents (12 years of age or older) with haemophilia A and inhibitors to factor VIII, in which emicizumab prophylaxis showed a statistically significant and clinically meaningful reduction in the number of bleeds over time compared to no prophylaxis, as well as compared to prior prophylaxis with bypassing agents. The most common adverse events with emicizumab in the HAVEN 2 study were injection site reactions and nasopharyngitis.
  • • On June 7, 2016, a Phase 3 trial sponsored by Roche was published on the NIH website ClinicalTrials.gov for emicizumab and is currently recruiting participants.

Is general: Yes