For many patients with hemophilia A, with or without inhibitors, a monthly emicizumab injection is enough to ensure a high level of bleed control, based on results from the ongoing HAVEN 4 trial.
Most patients reported three or fewer treated bleeds, while slightly more than half had no treated bleeds at all, according to lead author Steven W. Pipe, MD, of the University of Michigan, Ann Arbor, and his colleagues. The investigators noted that results from this trial have already led to approval of a monthly dosing schedule in the United States and several other countries.
“This convenient regimen has the potential to improve the care of patients by decreasing their treatment burden, and increasing uptake and adherence to effective prophylaxis, which is known to decrease the development of debilitating secondary complications,” the investigators wrote. The report is in The Lancet Haematology.
The data were collected at 20 centers in 8 countries. Eligibility required that patients have severe congenital hemophilia A (less than 1% normal FVIII activity), or hemophilia A with FVIII inhibitors and concurrent treatment with bypassing agents or FVIII concentrates.
An initial run-in cohort that included seven patients assessed pharmacokinetics and safety. These patients received 6 mg/kg of emicizumab subcutaneously every 4 weeks for at least 24 weeks. After this group showed good responses, 41 additional patients were enrolled in an expansion cohort, which involved an initial loading phase of weekly doses at 3 mg/kg for the first month, followed by monthly dosing at 6 mg/kg for at least 6 months (24 weeks).
The efficacy endpoint of the study was bleed prevention, as measured by treated target joint bleeds, treated joint bleeds, treated spontaneous bleeds, all bleeds (untreated and treated), and annualized bleed rates for treated bleeds.
In the expansion cohort, the median number of bleeds in the 24-week period preceding enrollment was five. In the same group, five patients (12%) had FVIII inhibitors and 61% of patients exhibited at least one target joint.
After a median treatment of 25.6 weeks, the model-based annualized bleed rate for treated bleeds was 2.4, while the median annualized bleed rate was zero.
Slightly more than half of the patients (56.1%) reported no treated bleeds, 90% of patients reported 0-3 treated bleeds, and 85% of patients did not require treatment for targeted joint bleeds.
When untreated bleeds were included, the model-based annualized bleed rate was 4.5, while the median annualized bleed rate was 2.1. Almost one-third of patients (29%) had no bleeding events of any kind and most (80%) had 0-3 treated or untreated bleeds.
Overall, treatment was well tolerated, with no patients withdrawing from the study, discontinuing treatment, or requiring dose modifications. Laboratory parameters remained stable throughout. The most common treatment-related adverse event was injection-site reaction (22%), followed distantly by pre-syncope, chills, rash, and erythema, each of which occurred in 2% of patients.
“Overall, the results of HAVEN 4 are consistent with the findings of other HAVEN studies,” the investigators wrote. “The option of treatment with emicizumab every 4 weeks broadens the range of administration frequencies and allows clinicians to tailor treatment to each patient’s needs and preferences.”
F. Hoffman-La Roche and Chugai funded the study. The investigators reported financial relationships with the study sponsors and other companies.
SOURCE: Pipe SW et al. Lancet Haem. 2019 Apr 16. doi: 10.1016/S2352-3026(19)30054-7.