Hemlibra Safely Prevents Bleeds in Hemophilia A Patients Over Long Term, Trial Data Show

Hemlibra (emicizumab) continues to safely and effectively prevent bleedings in children and adults with hemophilia A, regardless of developing neutralizing inhibitors (antibodies) against synthetic factor VIII (FVIII), according to nearly three years of data from four Phase 3 clinical trials.

These and preliminary real-world safety findings from a European database will be presented in two Roche-sponsored posters during the 62nd American Society of Hematology Annual Meeting and Exposition, being held virtually Dec. 5–8. Hemlibra was developed by Chugai Pharmaceutical and Genentech, two subsidiaries of Roche.

“We have one of the largest clinical development programs in malignant and non-malignant hematology and we continuously seek to improve patient outcomes by exploring new therapeutic mechanisms, combinations and clinical trial endpoints,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, said in a press release.

“Our data reflect our ongoing commitment to following the science and improving the lives of patients with some of the most difficult-to-treat blood disorders,” he added.

Administered as an under-the-skin injection, Hemlibra works by binding to both factor IX and factor X to mimic the activity of FVIII — the missing or defective clotting factor in hemophilia A patients — helping blood to clot normally.

The therapy is approved in more than 90 countries as a routine preventive treatment for people with hemophilia A and FVIII inhibitors. It also is approved globally, including in the U.S., Europe, and Japan, as a preventive treatment for those without inhibitors.

Hemlibra’s safety and effectiveness in preventing bleeds was established in a clinical program comprising 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 side effects, including blood clot-related complications.

Now, evidence of Hemlibra’s long-term effectiveness and safety from nearly three years of follow-up data from the HAVEN program will be presented in the poster, “Safety and Efficacy of Emicizumab in Persons with Hemophilia a with or without FVIII Inhibitors: Pooled Data from Four Phase III Studies (HAVEN 1–4).”

The analysis included 400 hemophilia A patients who received at least one shot of Hemlibra during the HAVEN study, representing a total of 970.3 patient-years (the sum of all patients’ follow-up years).

Patients’ median age at enrollment was 28.5 (range 1–77 years), with most being white (66.8%) or Asian (18.8%), and 52.3% having FVIII inhibitors.

The median duration of treatment was 120.4 weeks (just under two and a half years), with 85% of participants being treated for at least 74 weeks (less than one and a half years). Eleven (2.8%) patients stopped taking Hemlibra over the course of the studies.

Results showed that the pooled annualized bleeding rate for bleeds requiring treatment remained low throughout the three years, decreasing every six months to 0.7.

During the last six months of the treatment period, more than 82% of patients had zero treated bleeds (82.4%), spontaneous bleeds (91.8%), or joint bleeds (90%); 15.3% had one to three treated bleeds.

In addition, the proportion of participants with target joints dropped from 60.9% prior to enrollment to 4.6% during the first six months of treatment and to less than 1.5% thereafter.

Hemlibra was generally well tolerated, with no new safety concerns identified. The proportion of patients reporting treatment-related side effects, including injection site reactions, dropped over time from more than 23% to 3% or less.

Three thrombotic microangiopathies (TMA) — damage of the smallest blood vessels due to blood clots — and two of the four blood clot-related complications reported during follow-up were associated with simultaneous use of activated prothrombin complex concentrate (aPCC).

Notably, the combined use of Hemlibra and aPCC was previously found to increase the risk of TMA or blood clot-related complications, leading to a warning in Hemlibra’s label and ongoing safety monitoring.

These current findings reinforce the long-term benefits and safety of Hemlibra in hemophilia A patients of all ages, with or without FVIII inhibitors, the researchers said.

Hemlibra’s favorable safety profile is also supported by new real-world data to be presented in the poster, “Real-World Safety of Emicizumab: The First Interim Analysis of the European Haemophilia Safety Surveillance (EUHASS) Database.”

Researchers conducted an early analysis of Hemlibra’s safety data from the European Haemophilia Safety Surveillance, a program that monitors the real-world safety of treatments for inherited bleeding disorders at 86 centers across 27 countries.

They analyzed the frequency of side effects reported for 148 hemophilia A patients, with and without FVIII inhibitors, treated with Hemlibra in 2018, of whom 22.3% were receiving other treatments at the same time.

Two adverse events were reported, according to the results. A temporary rash occurred in a patient treated with Hemlibra alone, and a blood clot-related heart attack in a patient older than 65 who was receiving Hemlibra and aPCC.

No TMA or anaphylaxis (a serious, potentially life-threatening allergic reaction) were reported, and no new safety concerns were identified.

“While a full assessment is reserved for the final analysis, these interim real-world data are not inconsistent with the adverse event profile of [Hemlibra] observed in clinical trials,” the researchers wrote.

Ten other Roche medicines for a number of malignant blood disorders will be featured in more than 80 abstracts during the conference.