HAVEN-2 confirms safety, efficacy of once-weekly emicizumab for paediatric haemophilia A with inhibitors
Once-weekly subcutaneous administration of the bispecific humanized monoclonal antibody emicizumab successfully prevented or reduced bleeds with a favourable safety profile in paediatric patients with haemophilia A with inhibitors in the phase III HAVEN-2* trial, confirming the findings of a previous interim analysis.
“These updated results from the HAVEN-2 study confirm the earlier results … that emicizumab successfully prevents or reduces bleeds and that we see clinically meaningful reductions in [annualized bleeding rate (ABR)] shown with emicizumab vs prior bypassing agent treatment,” said study lead author Dr Guy Young, director of the haemostasis and thrombosis programme at the Children’s Hospital Los Angeles and University of Southern California, California, US, who presented the findings at ASH 2017.
Results of the previous interim analysis involving 20 children aged 3–12 years (or 12–17 years if <40 kg) with haemophilia A with inhibitors who previously received episodic or prophylactic treatment with bypassing agents showed that prophylactic subcutaneous emicizumab QW (3 mg/kg/week for 4 weeks [loading dose] and 1.5 mg/kg/week thereafter) reduced or prevented the risk of treated bleeds compared with prior treatment with bypassing agents. [ISTH 2017, abstract OC 24.1, Res Pract Thromb Haemost 2017;1:1-15]
The current analysis included an additional 40 patients (median age 7 years, all male, 95 percent with severe haemophilia) who were observed for a median 9 weeks (20 patients were observed for ≥24 weeks). About seventy-three percent of patients were on prophylactic bypass agents at study entry. The 57 patients aged <12 years were included in the efficacy analysis while the safety analysis included all 60 patients.
Almost 95 percent (94.7 percent) of patients had zero bleeds requiring treatment with bypass agents (treated bleeds; n=54) while 64.9 percent of patients did not experience any bleeds. [ASH 2017, abstract OA 85]
Of the 23 patients aged <12 years who were followed up for ≥12 weeks (median follow-up 38.1 weeks), 34.8 percent had no bleeding events while 87 percent had no treated bleeds and 95.7 percent had no joint bleeds. Of 13 patients in this group who were previously included in a noninterventional study, there was a 99 percent reduction in ABR with emicizumab prophylaxis vs prior treatment with bypass agents.
There were 201 adverse events reported in 40 patients; six of these were considered serious and comprised muscle haemorrhage, mouth haemorrhage, eye pain, catheter-site infection, device-related infection, and appendicitis. There were no thromboembolic or thrombotic microangiopathy events reported and none of the patients tested positive for antidrug antibodies.
“Approximately 30 percent of … patients [with haemophilia A] will develop neutralizing alloantibodies and … these inhibitors significantly increase morbidity and decrease health-related quality of life,” said Young.
Currently available treatments for haemophilia A with inhibitors are immune tolerance induction and bypass agents. However, intravenous infusions often require the use of central venous access devices over a long-term period “which may be complicated by infections and thrombosis”, he said.
“Before this drug, we didn’t have very effective ways to prevent joint bleeding in these patients. This drug has demonstrated a very high level of efficacy at preventing those bleeding events. It’s been life-changing for the children I’ve treated,” said Young.