Long‐term safety and efficacy of emicizumab for up to 5.8 years and patients’ perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A

Abstract

Introduction Safety and efficacy results of the phase 1 study and phase 1/2 extension study of the bispecific antibody emicizumab in patients with severe haemophilia A with or without factor VIII inhibitors for up to 2.8 years were reported previously. Aim To evaluate further longer‐term data including patients’ perceptions at study completion. Methods Emicizumab was administered subcutaneously once weekly at maintenance doses of 0.3, 1 or 3 mg/kg with potential up‐titration. All patients were later switched to the approved maintenance dose of 1.5 mg/kg. Results Eighteen patients received emicizumab for up to 5.8 years. Most adverse events were mild and unrelated to emicizumab. Annualized bleeding rates (ABRs) for bleeds treated with coagulation factors decreased from pre‐emicizumab rates or remained zero in all patients. The median ABRs were low at 1.25, 0.83 and 0.22 during the 0.3, 1 and 3 mg/kg dosing periods, respectively. Of 8 patients who decreased their doses from 3 to 1.5 mg/kg, ABRs decreased in 4, remained at zero in 2, and increased in 2. Total time spent with symptoms associated with treated bleeds decreased in all patients except 2. All patients answered ‘improved’ for bleeding severity and time until bleeding stops, except 1 answering ‘slightly improved’. Most patients answered ‘improved’ or ‘slightly improved’’ for daily life and feelings; in particular, all patients except 1 answered ‘improved’ or ‘slightly improved’ for anxiety. Conclusions Long‐term emicizumab prophylaxis for up to 5.8 years was safe and efficacious, and may improve patients’ daily lives and feelings, regardless of inhibitor status.

Emicizumab for All Pediatric Patients with Severe Hemophilia A

“…This long-term observation could show the remarkable efficacy as well as safety of emicizumab, and thus highlights the improvement with regard to the severity and quantity of bleeding-associated symptoms, daily life, and mental health. 32…”

“…The longest reported observation time is around 3 years in HAVEN 1-4 and 5.8 years in the phase 1 and 1/2 dose finding study. 31,32 Additionally, it is regularly discussed how important peak levels are for long-term outcome. Is emicizumab prophylaxis sufficient for high activity sports to prevent bleedings, or do we need peak levels?…”

Haemophilia: factoring in new therapies

“…Additionally, patients reported improved health‐related QoL with 100% preference of emicizumab over prior therapies in adolescents and adults without inhibitors in HAVEN 4 38 . Long‐term safety data continues to be collected with 5·8 years of data currently available and ongoing surveillance studies 41 . There is ongoing post‐marketing vigilance for thrombosis or TMA, but it is recommended to avoid co‐administration of bypassing agents and limit aPCC dosing to <100 unit/kg/day based on limited published cases 36,42 …”

“…38 Long-term safety data continues to be collected with 5Á8 years of data currently available and ongoing surveillance studies. 41 There is ongoing post-marketing vigilance for thrombosis or TMA, but it is recommended to avoid co-administration of bypassing agents and limit aPCC dosing to <100 unit/kg/day based on limited published cases. 36,42 Several clinical studies are ongoing and/or planned to continue to evaluate and expand the use of emicizumab in additional populations.…”

Studies on factor VIII toward a new therapeutic for hemophilia A

“…Assessments of long-term safety and efficacy of new therapeutics are crucial. Eighteen patients who participated in the phase 1 and phase 1/2 extension trials received emicizumab for up to 5.8 years 36,44,45) . In the phase 1 investigations, six patients were enrolled in each of three dosing groups; 0.3 mg/kg, 1 mg/kg and 3 mg/kg QW groups.…”