Roche : FDA advisory committee unanimously recommends approval of Roche’s subcutaneous rituximab for certain blood cancers

Basel, 30 March 2017

FDA advisory committee unanimously recommends approval of Roche's subcutaneous rituximab for certain blood cancers

• The FDA has set an action date of June 26 to make a final decision on approval

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) voted unanimously (11 to 0) that the benefit-risk of rituximab/hyaluronidase for subcutaneous (under the skin) injection was favourable for the treatment of certain blood cancers, which include: previously untreated follicular lymphoma, previously untreated diffuse large B-cell lymphoma (DLBCL), relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory chronic lymphocytic leukemia (CLL). This new co-formulation includes the same monoclonal antibody as intravenous Rituxan® (rituximab) and hyaluronidase, a molecule that helps to deliver medicine under the skin. The FDA is expected to make a decision on approval by June 26, 2017.

'Subcutaneous rituximab can be administered in five to seven minutes compared to an hour and a half or more for intravenous Rituxan,' said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. 'The significant reduction in administration time could especially benefit people with blood cancer who may receive years of treatment, and we are pleased the committee unanimously supported this new co-formulation.'

This co-formulation has been available in the European Union since 2014 where it is known as the subcutaneous (SC) formulation of MabThera® (rituximab) and is approved in approximately 50 other countries worldwide. In the United States, Rituxan is currently approved as an intravenous formulation for the treatment of people with previously untreated follicular lymphoma, previously untreated DLBCL, relapsed or refractory low grade or follicular lymphoma, and previously untreated and relapsed or refractory CLL. Intravenous Rituxan will continue to be available to patients if subcutaneous rituximab is approved. The committee's vote does not affect intravenous Rituxan's approved uses in the United States or in other countries.

The ODAC recommendation was based on a review of results from a clinical development program comprising five studies that together represented more than 2,000 people across key blood cancers for which intravenous Rituxan is approved. Because the monoclonal antibody in subcutaneous rituximab and intravenous Rituxan is the same, it was possible to utilize clinical studies that linked the safety and efficacy profile of the subcutaneous co-formulation to the well-established profile of intravenous Rituxan. The studies demonstrated that subcutaneous administration of the co-formulation resulted in non-inferior levels of rituximab in the blood (pharmacokinetics) and consistent clinical efficacy and safety outcomes compared to intravenous Rituxan. The clinical program also assessed patient preferences for subcutaneous rituximab and healthcare provider opinions. The studies were the following:

• SparkThera (NCT00930514): Phase Ib maintenance study in previously untreated or relapsed follicular lymphoma
• SABRINA (NCT01200758): Phase III induction and maintenance study in previously untreated follicular lymphoma
• SAWYER (NCT01292603): Phase Ib study in previously untreated CLL
• MabEase (NCT01649856): Phase III study in previously untreated DLBCL
• PrefMab (NCT01724021): Phase III patient preference study in previously untreated follicular lymphoma and DLBCL

Data from these studies were included in the company's Biologics License Application for subcutaneous rituximab submitted to the FDA.

About MabThera/Rituxan (rituximab)

MabThera/Rituxan is a therapeutic monoclonal antibody that binds to a particular protein - the CD20 antigen - on the surface of normal and malignant B-cells. It then recruits the body's natural defenses to attack and kill the marked B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.

Rituxan first received FDA approval for the treatment of relapsed indolent non-Hodgkin Lymphoma (NHL) in 1997 and was the first targeted cancer medicine approved by the U.S. Food and Drug Administration (FDA). MabThera was approved in the EU in June 1998, and has since been used to treat more than 2.7 million people with specific blood cancers. For more than 15 years, the efficacy and safety of MabThera/Rituxan has been documented in more than 300 phase II/III clinical studies. MabThera/Rituxan has been approved for the treatment of several blood cancers, specifically, certain types of NHL and for chronic lymphocytic leukemia (CLL). It continues to be studied in other types of blood cancers and disease areas where CD20-positive cells are believed to play a role.

MabThera is known as Rituxan in the United States, Japan and Canada. Genentech, a member of the Roche Group, and Biogen collaborate on Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where MabThera is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.

About subcutaneous rituximab

Subcutaneous rituximab is investigational in the United States. It is a co-formulation of the same monoclonal antibody as intravenous MabThera/Rituxan and recombinant human hyaluronidase (rHuPH20), a technology licensed from Halozyme Therapeutics, Inc. Hyaluronidase is an FDA-approved molecule that facilitates the delivery of a relatively large volume of medicine under the skin. The subcutaneous co-formulation can be administered in five to seven minutes, compared to 1.5 to four hours for intravenous MabThera/Rituxan. It is known as the subcutaneous (SC) formulation of MabThera® (rituximab) in the European Union.

About Roche in haematology

For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. 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 VenclextaTM/VenclyxtoTM (venetoclax) in collaboration with AbbVie, Roche's pipeline of investigational haematology 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 haematology expands beyond malignancy, with the development of the investigational haemophilia A treatment emicizumab.

About Roche

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.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Twenty-nine medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry eight years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. 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.

References
1. Rituxan® (rituximab) is marketed as MabThera® (rituximab) outside the United States, Canada and Japan.