#ISTH2020 – Hemlibra Continues to Show Favorable Safety Profile, Early Phase 3b Trial Data Show

Note: This story was updated July 20, 2020, to note that Hemlibra binds to activated FIX and FX, rather than to FIX and FX.

When given as preventive treatment to avoid spontaneous bleeds in people with hemophilia A with inhibitors, Hemlibra (emicizumab) continues to show a favorable safety profile that is consistent with previous reports, a second analysis from the Phase 3b STASEY clinical trial shows.

In addition, a separate analysis from STASEY (NCT03191799) showed that patients receiving Hemlibra may be able to undergo minor surgeries safely without having to receive additional prophylactic treatment, while major surgical procedures may be managed with the help of blood-clotting concentrates.

The early data from STASEY, including safety analyses and patient surgical outcomes, were presented at the 2020 Congress of the International Society on Thrombosis and Haemostasis, held virtually this week.

Genentech’s Hemlibra is a bi-specific antibody, meaning that it has the ability to bind to two different targets simultaneously. The therapy mimics how the blood clotting protein factor VIII (FVIII), which is missing in people with hemophilia A, works in the body by binding to the activated form of clotting factor IX (FIX) and to factor X (FX) to allow for proper blood coagulation.

The medication has been approved as a routine preventive treatment for patients with hemophilia A with FVIII inhibitors — neutralizing antibodies that render conventional FVIII replacement therapies useless — in more than 90 countries worldwide. It also is approved globally, including the U.S., Europe, and Japan, as a prophylactic treatment for patients without FVIII inhibitors.

Hemlibra’s safety and effectiveness in preventing bleeds in people with hemophilia A, with and without inhibitors, was established in a clinical program encompassing four Phase 3 trials: HAVEN 1 (NCT02622321), HAVEN 2 (NCT02795767), HAVEN 3 (NCT02847637), and HAVEN 4 (NCT03020160).

Data from the HAVEN program showed that Hemlibra lowered the number of bleeds without causing major adverse events (side effects), including thrombotic events (blood clots that clog blood vessels).

STASEY is an open-label Phase 3b trial that aims to confirm the safety and tolerability profile of Hemlibra in 195 patients with hemophilia A with FVIII inhibitors, ages 12 and older.

During the trial, participants received prophylactic treatment with Hemlibra, administered by an injection under the skin, starting at a weekly dose of 3 mg/kg for four weeks, followed by a weekly maintenance dose of 1.5 mg/kg for the remaining two years of the study.

With a cut-off date of May 20, 2019, a second preliminary analysis of STASEY including 193 patients (median age 28) who had been receiving Hemlibra for an average of 50.9 weeks, showed that treatment was effective at preventing bleeding episodes, with 85.6% of the patients having no bleeds requiring treatment. This was consistent with previous observations from HAVEN trials.

None of the participants in STASEY experienced thrombotic microangiopathy or serious thrombotic events related to Hemlibra, which also was consistent with previous safety data. No new safety concerns were identified.

The most common adverse events included nasopharyngitis, or common cold (12.4%), headache (11.9%), and injection site reactions (11.4%). In most cases, side effects were mild or moderate in severity and did not cause patients to discontinue treatment.

One participant died during the trial from polytrauma (multiple traumatic injuries) that was deemed unrelated to Hemlibra.

“These important safety data continue to add to the extensive clinical evidence reinforcing Hemlibra’s potential to redefine the standard of care for people with hemophilia A,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a press release.

Results from a separate analysis from STASEY, which focused on clinical outcomes in a sub-group of patients who underwent surgery during the study, also were  presented at the virtual congress.

The analysis, which included 31 minor procedures in 22 patients and nine unplanned major surgeries in eight participants, showed that 20 patients (64.5%) having minor surgical procedures did not require additional prophylactic treatment, and only three (15%) required post-operative treatment to control bleeds.

From the nine major surgeries, eight were managed with additional prophylactic treatment, and four required post-operative treatment to manage bleeds. These findings were consistent with surgical outcomes reported in previous studies, said Genentech.

“The STASEY study reflects our continued focus on providing valuable insights that meet the needs of the hemophilia community and enhance our understanding of Hemlibra in clinical practice,” Garraway said.