TOKYO, May 21, 2018 -- Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) today announced that full results from the HAVEN 3 study (NCT02847637) and HAVEN 4 study (NCT03020160) evaluating Chugai’s hemophilia A treatment HEMLIBRA^® [generic name: emicizumab (genetical recombination)] are being presented at the World Federation of Hemophilia 2018 World Congress held in Glasgow, Scotland from May 20 to 24. HAVEN 3 study is conducted in people with hemophilia A without inhibitors, and HAVEN 4 study is conducted in people with hemophilia A with or without inhibitors. Results from both studies will be presented as late-breaking abstracts.

“The results from HAVEN 3 study demonstrate that HEMLIBRA, which was created with Chugai’s proprietary antibody engineering technologies, can reduce the bleeding risk in people with hemophilia A without inhibitors. The intra-patient comparison in this study also shows a statistically significant reduction in bleeding by HEMLIBRA prophylaxis compared to factor VIII therapy, the current standard treatment,” said Chugai’s President & CEO, Tatsuro Kosaka. “In addition, HAVEN 4 data indicates that regardless of the presence of inhibitors, HEMLIBRA administration once every four weeks can reduce the risk of bleeding in people with hemophilia A compared with existing treatments. We will closely work with Roche to obtain approval of HEMLIBRA for the treatment of hemophilia A without inhibitors as early as possible.”

HAVEN 3 Study

Study description

Study design n=152

• Patients previously treated with episodic factor VIII therapy were randomized in a 2:2:1 fashion to either Arm A, B or C

  Arm A (n=36)	Received HEMLIBRA prophylaxis at 3 mg/kg by once-weekly subcutaneous injection for 4 weeks, followed by 1.5 mg/kg once-weekly subcutaneous injection
  Arm B (n=35)	Received HEMLIBRA prophylaxis at 3 mg/kg by once-weekly subcutaneous injection for 4 weeks, followed by 3 mg/kg once every two weeks subcutaneous injection
  Arm C (n=18)	No prophylaxis control arm

• Patients previously treated with factor VIII prophylactic were enrolled in:

  Arm D (n=63)

  Received HEMLIBRA prophylaxis at 3 mg/kg by once-weekly subcutaneous injection for 4 weeks, followed by 1.5 mg/kg once-weekly subcutaneous injection

Episodic treatment of breakthrough bleeds with factor VIII therapy was allowed per protocol.

Summary of results

• HEMLIBRA achieved a statistically significant reduction in treated bleeds by 96% (Wald test, p <0.0001) with once-weekly prophylaxis of HEMLIBRA (Arm A) and 97% (p <0.0001) with once every two weeks prophylaxis respectively, compared with no prophylaxis control arm (Arm C).

[Major secondary endpoints and reduction rate (%)] (Wald test)

• 55.6% (95% CI: 38.1, 72.1) of patients receiving once-weekly prophylaxis of HEMLIBRA (Arm A) experienced zero treated bleeds and 60% (95% CI: 42.1, 76.1) of patients receiving once every two weeks prophylaxis of HEMLIBRA (Arm B) compared to 0% (95% CI: 0.0, 18.5) of those not receiving prophylaxis treatment (Arm C).
• An intra-patient comparison (n=48) in patients who had previously treated with factor VIII prophylaxis prior to the study (Arm D) and participated in the foregoing non-interventional study (NIS) showed that 68% (RR=0.32, p <0.0001) reduction of treated bleeds with once-weekly prophylaxis of HEMLIBRA.
• Adverse events (AEs) occurring in 5% or more of patients treated with HEMLIBRA were injection site reactions, joint pain (arthralgia), common cold symptoms (nasopharyngitis), headache, upper respiratory tract infection and influenza.
• There were no unexpected or serious adverse events (AEs) related to HEMLIBRA and most common AE profiles appeared consistent with the known safety profile of the medicine.

HAVEN 4 Study

Study Description

Study design n=48

Summary of results

• Patients receiving HEMLIBRA prophylaxis in Expansion cohort had a median annualized bleeding rate (ABR) for treated bleeds of 0.0 (IQR: 0.0; 2.1).
• 56.1% (95% CI: 39.7, 71.5) of patients in Expansion cohort achieved zero treated bleeds and 90.2% (95% CI: 76.9, 97.3) of patients experienced three or fewer treated bleeds.

[Major secondary endpoints and achievement rate (%) of zero bleeds]

• Results from HAVEN 4 study is consistent with results obtained from other phase III studies of HEMLIBRA. These data show that once every 4 weeks prophylaxis of HEMLIBRA can provide clinically meaningful control of bleeding in patients with hemophilia A with or without factor VIII inhibitors.
• There were no unexpected or serious adverse events (AEs) related to HEMLIBRA and the most common AEs were consistent with previous studies.
• Injection site reaction was the most common AE, occurring in nine people.

Summary of the HAVEN 3 (NCT02847637) study results presented at WFH

*Negative binomial regression model

Summary of the HAVEN 4 (NCT03020160) study results presented at WFH

About Chugai
Chugai Pharmaceutical is one of Japan’s leading research-based pharmaceutical companies with strengths in biotechnology products. Chugai, based in Tokyo, specializes in prescription pharmaceuticals and is listed on the 1st section of the Tokyo Stock Exchange. As an important member of the Roche Group, Chugai is actively involved in R&D activities in Japan and abroad. Specifically, Chugai is working to develop innovative products which may satisfy the unmet medical needs, mainly focusing on the oncology area.
In Japan, Chugai’s research facilities in Gotemba and Kamakura are collaborating to develop new pharmaceuticals and laboratories in Ukima are conducting research for technology development for industrial production. Overseas, Chugai Pharmabody Research based in Singapore is engaged in research focusing on the generation of novel antibody drugs by utilizing Chugai’s proprietary innovative antibody engineering technologies. Chugai Pharma USA and Chugai Pharma Europe are engaged in clinical development activities in the United States and Europe.
The consolidated revenue in 2016 of Chugai totalled 491.8 billion yen and the operating income was 80.6 billion yen (IFRS Core basis).
Additional information is available on the internet at https://www.chugai-pharm.co.jp/english.

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