Investor Update

Basel, 23 June 2015

Roche announces further encouraging data from study of ACE910 in adults and adolescents with severe haemophilia A

  • Data from Phase I extension study presented at major medical conference on bleeding disorders showed that reduction in bleeding rates was maintained after a follow-up of 5.6 to 18.5 months
  • ACE910 is the first FVIIIa-mimetic bispecific antibody to have shown potential benefit in people with severe haemophilia A both with or without inhibitors to factor VIII

Roche (SIX: RO, ROG; OTCQX: RHHBY) yesterday announced new data from the first study of the novel humanised bispecific antibody ACE910 (RG6013) in people with severe haemophilia A at the International Society on Thrombosis and Haemostasis (ISTH) annual meeting. This is a long-term follow-up of the Phase I study presented at the annual meeting of the American Society of Hematology (ASH) in 2014, which reported data for the first 12 weeks of treatment. New data from the open-label Phase I extension study suggested that once-weekly subcutaneous administration of ACE910 had a promising prophylactic efficacy profile in people with severe haemophilia A, after a follow-up of 5.6 to 18.5 months. The tolerability profile of ACE910 was consistent with that previously observed in the Phase I study data presented last year.

“After longer follow-up, the data showed that people with severe haemophilia A who were treated with ACE910 continued to experience fewer bleeding events compared to the six months before they began treatment,” said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are encouraged by these early data and are moving the ACE910 development program forward as fast as possible to address the needs of people with haemophilia A. Our goal is to initiate a Phase III trial in patients with factor VIII inhibitors by the end of 2015 and a Phase III trial in patients without inhibitors in 2016.”

ACE910’s effectiveness irrespective of the presence of factor VIII inhibitors is meaningful because approximately one in every four people with severe haemophilia A develops these inhibitors to factor VIII.i Despite currently available therapies, the formation of inhibitors is one of the major challenges affecting people with severe haemophilia A and there remains a need for effective treatment options for these patients.ii

Patients who received ACE910 treatment in the ongoing Phase I study showed a significant reduction in annualised bleeding rate (ABR) after a follow-up of 5.6 to 18.5 months, compared to the rate demonstrated in the 6-month period before study enrolment. As shown in the table below, the median ABR was reduced in all cohorts in patients with or without factor VIII inhibitors.

The data from this study were presented at the International Society on Thrombosis and Haemostasis (ISTH) annual meeting in Toronto, Canada in an oral presentation by Dr. Keiji Nogami from Nara Medical University in Japan (Abstract 1283; 22 June 2015 at 16.30 EDT).

About the ACE910 Phase I trial

Patient profile

  • Japanese patients with severe haemophilia A (FVIII: C<1%, ages 12 to 58 years).
  • Once-weekly subcutaneous ACE910 at one of the following dose levels for a follow-up of 5.6 to 18.5 months: 0.3 mg/kg (Cohort-1), 1 mg/kg (Cohort-2) and 3mg/kg (Cohort-3).
  • The number of patients with FVIII inhibitors was 4, 4 and 3, respectively, for the 0.3 mg/kg, 1 mg/kg and 3 mg/kg dose levels.

Safety data

  • The tolerability profile of ACE910 was consistent with that previously observed in the Phase I study.
  • A total of 93 adverse events (AEs) were observed in all 18 patients; all were of mild or moderate intensity.
  • One patient discontinued ACE910 administration due to injection site redness of mild intensity.
  • No thromboembolic AEs were observed, even when ACE910 was given concomitantly with FVIII products or bypassing agents as episodic treatment for breakthrough bleeds.
  • Anti-ACE910 antibodies, which did not affect ACE910 pharmacokinetics or pharmacodynamics, were developed in three patients.

Efficacy data

Treatment armNAnnualised bleeding rate (ABR) reduction
Cohort-1
0.3mg/kg ACE910
2/6 without FVIII inhibitors
4/6 with FVIII inhibitors
22.8%-82.7%
49.3%-100%
Median ABR change (all bleedings): 32.5→1.7
Cohort-2
1mg/kg ACE910
2/6 without FVIII inhibitors
4/6 with FVIII inhibitors
79.6%-100%
87.0%-100%
Median ABR change (all bleedings): 18.3→0
Cohort-3
3mg/kg ACE910
3/6 without FVIII inhibitors
3/6 with FVIII inhibitors
0%*-100%
93.0%-100%
Median ABR change (all bleedings): 15.2→0

*One patient did not report bleeding episodes at baseline nor during the conduct of this study.

About ACE910

ACE910 is an investigational humanised FVIIIa-mimetic bispecific monoclonal antibody engineered to simultaneously bind factors IXa and X. ACE910 thereby mimics the cofactor function of factor VIII in severe haemophilia A patients who are deficient in this blood clotting protein and may promote blood coagulation under conditions where FVIII is lacking. ACE910 therefore has the potential to help overcome medical problems such as the development of factor VIII inhibitors and the need for frequent venous access which is regularly encountered in severe haemophilia A patients. ACE910 was created by Chugai Pharmaceutical Co., Ltd. and was opted into by Roche in 2014.

About Roche in haematology

For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we’re 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) and Gazyva®/Gazyvaro® (obinutuzumab), Roche’s pipeline of investigational haematology medicines includes an anti-CD79b antibody drug conjugate (RG7596/polatuzumab vedotin), a small molecule antagonist of MDM2 (RG7112), and, in collaboration with AbbVie, a small molecule BCL-2 inhibitor (venetoclax/RG7601/GDC-0199/ABT-199). Roche’s dedication to developing novel molecules in haematology expands beyond oncology, with the development of the investigational haemophilia A treatment ACE910.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-eight medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2014, the Roche Group employed 88,500 people worldwide, invested 8.9 billion Swiss francs in R&D and posted sales of 47.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References
i) Astermark, J. Overview of Inhibitors. Semin Hematol 43(suppl 4):S3-S7; 2006.
ii) Kempton, CL and White, GC. How we treat a hemophilia A patient with a factor VIII inhibitor. Blood 2009; 113: 11-17.