Health Canada Approves Hemlibra® for Hemophilia A Patients Without Factor VIII Inhibitors

Hemlibra is the only treatment that can be self-injected subcutaneously once weekly for patients with hemophilia A without factor VIII inhibitors(1)

MISSISSAUGA, ON, June 18, 2019 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) announced today that Health Canada has approved Hemlibra(®) (emicizumab injection) for hemophilia A (congenital factor VIII deficiency) patients without factor VIII inhibitors as routine prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes.(2) Limited data exists for patients suffering from mild and moderate hemophilia A. (Please see Hemlibra product monograph for full prescribing information). The announcement follows last year's approval of Hemlibra for hemophilia A patients with factor VIII inhibitors.

The efficacy and safety of Hemlibra has been demonstrated by one of the largest clinical trial programmes ever conducted in hemophilia A patients, with and without factor VIII inhibitors, in four pivotal HAVEN studies (HAVEN 1, HAVEN 2, HAVEN 3, HAVEN 4).(3) Health Canada's approval of Hemlibra for hemophilia A patients without inhibitors is primarily based on positive results from two clinical studies, HAVEN 3 and HAVEN 4. HAVEN 3 demonstrated that Hemlibra substantially reduced bleeds in adults and adolescents compared to prior episodic (on demand) or prophylactic treatment with factor VIII.(4,5 )Health Canada also approved Hemlibra for use at multiple dosing options - once weekly, bi-weekly and, for adults and adolescents only, four-week dosing - for people with hemophilia A, including those with and without factor VIII inhibitors based on evidence from HAVEN 3 and 4.(6)

"Hemlibra represents an exciting new option for all patients with Hemophilia A," said Dr. Jayson Stoffman, Medical Director, Manitoba Bleeding Disorders Program. "I look forward to the opportunity to offer my patients something that could have an important impact on their quality of life and hemophilia management."

Hemophilia A is a rare bleeding disorder affecting approximately 3,000 Canadians,(7) predominantly male, causing significantly lower than normal levels of the protein factor VIII in the blood, in turn lowering the ability of the blood to clot.(8) Approximately 95 per cent of hemophilia A patients do not have factor VIII inhibitors.(9)

"It is great news that Hemlibra has now received an indication for people with hemophilia A without inhibitors," said Paul Wilton, President of the Canadian Hemophilia Society. "Based on the research we have seen, we are convinced that a number of Canadians may benefit from this new treatment option."

About the Health Canada Approval
HAVEN 3 was a randomized, multicenter, open-label phase III clinical study in 152 adolescent and adult males over the age of 12 with hemophilia A without FVIII inhibitors who had previously received either episodic (on-demand) or prophylactic treatment with factor VIII. In the study, patients received subcutaneous Hemlibra, 3 mg/kg once weekly for the first four weeks, followed by either 1.5 mg/kg once weekly (Arms A and D) or 3 mg/kg every two weeks (Arm B) after that, or no prophylaxis (Arm C).(10)

HAVEN 3 met its primary endpoint and key secondary endpoints. Data from the study showed:(11)

    --  Hemlibra prophylaxis once weekly or every two weeks resulted in a 96%
        (95% CI: 92.5; 98.0, p<0.0001) and 97% (95% CI: 93.4; 98.3, p<0.0001)
        reduction in treated bleeds, respectively, compared to episodic factor
        VIII.
    --  55.6% (95% CI: 38.1; 72.1) of people treated with Hemlibra once weekly
        and 60% (95% CI: 42.1; 76.1) of people treated with Hemlibra every two
        weeks experienced zero treated bleeds, compared to 0% (95% CI: 0.0;
        18.5) of people treated with episodic factor VIII.
    --  Patients treated with Hemlibra experienced less treated target joint
        bleeds, compared to the no prophylaxis arm. The ABR (95% CI) was 0.6
        (0.3; 1.4), 0.7 (0.3; 1.6) and 13.0 (5.2; 32.3) for Arm A (Hemlibra 1.5
        mg/kg QW), Arm B (Hemlibra 3 mg/kg Q2W) and Arm C (no prophylaxis),
        respectively.
    --  Patients with zero treated target joint bleeds (95% CI) comprised 69.4%
        (51.9; 83.7), 77.1% (59.9; 89.6) and 27.8% (9.7; 53.5) of the patients
        in Arm A (Hemlibra 1.5 mg/kg QW), Arm B (Hemlibra 3 mg/kg Q2W) and Arm C
        (no prophylaxis), respectively.
    --  Hemlibra prophylaxis once weekly or every two weeks resulted in a 95%
        (95% CI: 90.1; 97.0, p<0.0001) and 94% (95% CI: 89.7; 97.0, p<0.0001)
        reduction in all bleeds, respectively, compared to episodic factor VIII.
    --  In HAVEN 3, the Hemlibra regimen demonstrated a statistically
        significant (p<0.0001) reduction in treated bleeds compared with
        previous FVIII prophylaxis collected in the non-interventional study
        before enrollment.
        --  The mean (NBR model) ABR for patients on Hemlibra and FVIII
            prophylaxis were 1.5 (95% CI: 1, 2.3) and 4.8 (95% CI: 3.2, 7.1),
            respectively.
        --  The median (IQR) ABR for patients on Hemlibra and FVIII prophylaxis
            were 0 (95% CI: 0, 2.1) and 1.8 (95% CI: 0, 7.6), respectively.
        --  The percentage of patients with zero bleeds on Hemlibra and FVIII
            prophylaxis were 54.2 (95% CI: 39.2; 68.6) and 39.6 (95% CI: 25.8;
            54.7), respectively.

HAVEN 4 was a single arm, multicenter clinical study in 41 adult and adolescent males (aged >= 12 years and >= 40 kg) with hemophilia A with or without FVIII inhibitors who previously received either episodic ("on demand") or prophylactic treatment with FVIII or bypassing agents or FVIII.(12)

HAVEN 4 is the first study to have demonstrated that Hemlibra effectively reduces bleeds based on a four-week dosing schedule, in both adult and adolescent patients with or without factor VIII inhibitors.

    --  In HAVEN 4, after a median observation time of 25.6 weeks, efficacy
        results in patients without factor VIII inhibitors were as follows:(13)
        --  52.8% (95% CI: 35.5; 69.6) experienced zero bleeds overall, which
            includes all treated bleeds.
        --  27.8% (95% CI: 14.2; 45.2) experienced zero bleeds overall, which
            consists of all bleeds
        --  83.3% (95% CI: 67.2; 93.6) experienced zero treated spontaneous
            bleeds
        --  69.4% (95% CI: 51.9; 83.7) experienced zero treated joint bleeds


        --  83.3% (95% CI: 67.2; 93.6) experienced zero treated target joint
            bleeds.
    --  The efficacy of Hemlibra for routine prophylaxis in patients with
        hemophilia A with FVIII inhibitors was evaluated at a median observation
        time of 26.1 weeks in a subgroup of 5 hemophilia A patients with FVIII
        inhibitors based on the bleed rate for bleeds requiring treatment with
        coagulation factors.
        --  Hemlibra prophylaxis resulted in an ABR (95% CI) for treated bleeds
            of 1.2 (0.1, 14.8) based on negative binomial regression.
        --  On Hemlibra prophylaxis with 6 mg/kg every 4 weeks, 4 patients with
            FVIII inhibitors had zero treated bleeds.
        --  Athough limited by small patient numbers, the efficacy of the 6
            mg/kg every 4-week maintenance dose is consistent with the results
            observed for this dosing regimen in hemophilia A patients without
            inhibitors.

The most common adverse reactions reported in more than or equal to 1% of patients from pooled clinical trials with Hemlibra were injection site reactions, arthralgia, headache, pyrexia, diarrhea and myalgia. (14)

About Hemophilia A
Hemophilia A is an inherited, serious disorder in which a person's blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia A affects around 3,000 Canadians,(15, )predominantly male, approximately 40 per cent of whom have a severe form of the disorder.(16) Approximately 95 per cent of hemophilia A patients do not have inhibitors to factor VIII.(17)

People with hemophilia A either lack or do not have enough of a clotting protein called factor VIII. Depending on the severity of their disorder, people with hemophilia A can bleed frequently, especially into their joints or muscles.(18) These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility, and long-term joint damage.(19) A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies.(20) Inhibitors are antibodies developed by the body's immune system that bind to and block the efficacy of replacement factor VIII,(21) making it difficult, if not impossible to obtain a level of factor VIII sufficient to control bleeding.

About Hemlibra(®) (emicizumab injection)
Hemlibra is an engineered humanized monoclonal modified immunoglobulin G4 (IgG4) antibody that bridges activated factor IX and factor X to restore the natural function of missing activated factor VIII that is needed for effective blood clotting. It has no structural relationship to FVIII and, as such, does not induce or enhance the development of direct inhibitors to FVIII.(22,23)

Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly, every two weeks or every four weeks (for adults and adolescents).(24)

Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche and Genentech. It is currently approved in the United States, the European Union and other countries for people with hemophilia A with and without factor VIII inhibitors.

Hemlibra received Health Canada approval in August 2018 for hemophilia A patients with inhibitors.

About Roche in Hematology
For more than 20 years, Roche has been developing medicines that redefine treatment in hematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera(®)/Rituxan® (rituximab), Gazyva(®)/Gazyvaro(®) (obinutuzumab), and Venclexta(®) /Venclyxto(®) (venetoclax) in collaboration with AbbVie, Roche's pipeline of investigational hematology medicines includes Tecentriq(®) (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche's dedication to developing novel molecules in hematology expands beyond malignancy, with the development of Hemlibra (emicizumab injection), a bispecific monoclonal antibody for the treatment of hemophilia A.

About Roche
Headquartered in Basel, Switzerland, Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare - a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Roche Canada was founded in 1931. The company employs over 1,000 people across the country, with its pharmaceuticals head office located in Mississauga, Ontario, and diagnostics division based in Laval, Quebec. Roche Canada is actively involved in local communities, investing in charitable organizations and partnering with healthcare institutions across the country. For more information, visit www.rochecanada.com.

All trade-marks mentioned are the property of their respective owners.

© Copyright 2019; Hoffmann-La Roche Limited

REFERENCES



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SOURCE Roche Canada