Roche's GAZYVARO (obinutuzumab) approved in Switzerland for patients with previously treated follicular lymphoma

Second approval for GAZYVARO in Switzerland

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the Swiss regulatory and supervisory authority (Swissmedic) has approved GAZYVARO (GA101, obinutuzumab) in a second indication. GAZYVARO was approved in 2014 for the first-line treatment of chronic lymphocytic leukaemia (CLL) in combination with chlorambucil chemotherapy in people with other medical conditions.¹

This approval for the treatment of follicular lymphoma applies to GAZYVARO given in combination with bendamustine followed by maintenance therapy with GAZYVARO (for a maximum of two years) to treat people with follicular lymphoma (FL) who did not respond to treatment with rituximab or a rituximab-containing regimen or whose disease worsened during or after such treatment.¹ GAZYVARO was granted fast-track review in this indication, a designation that highlights the importance of this approval for a group of patients that is difficult to treat.

Follicular lymphoma (FL) is the most common indolent (slow-growing) form of a blood cancer known as non-Hodgkin lymphoma (NHL). Follicular lymphoma is considered incurable and relapse is common. People with FL are given many therapies in the course of their disease and must expect their disease to progress.

The approval is based on results from the Phase III GADOLIN study of people with follicular lymphoma whose disease progressed following prior therapy with rituximab. In this pivotal study, median progression-free survival was more than doubled with treatment with GAZYVARO plus bendamustine compared to treatment with bendamustine alone.² "This approval represents a significant advance as it gives patients with this disease an additional treatment option," says Prof. Christoph Mamot, Head of Oncology and Chairman of the Oncology Centre Mittelland, Cantonal Hospital Aarau.

The safety profile of GAZYVARO was evaluated based on 392 people with indolent NHL who took part in the GADOLIN study. The most common side effects of GAZYVARO were infusion reactions, low white blood cell count, nausea, fatigue, cough, diarrhoea, constipation, fever, low platelet count, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinus infection, low red blood cell count, general weakness and urinary tract infection. The most common Grade 3-4 side effects of the GAZYVARO regimen were low white blood cell count, infusion-related reactions and low platelet count.

This approval for recurrent/resistant follicular lymphoma means that GAZYVARO is approved in Switzerland to treat two common types of blood cancer. GAZYVARO is also approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia (CLL).

About the GADOLIN study²

GADOLIN (NCT01059630, GA04753g) is a phase III open-label, multicentre, randomised two-arm study evaluating GAZYVARO plus bendamustine followed by GAZYVARO alone until disease progression or for up to two years compared to bendamustine alone. The study included 396 patients with indolent non-Hodgkin lymphoma (NHL), among them 321 patients with follicular lymphoma whose disease progressed during or within six months of prior treatment with MabThera (rituximab). The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee, secondary endpoints including PFS as assessed by investigator review, best overall response (BOR), complete response CR), partial response PR), duration of response, overall survival (OS) and safety profile. Results in follicular lymphoma showed:

• The GAZYVARO regimen improved progression-free survival (PFS) compared to bendamustine alone, as assessed by an independent review committee (mPFS (IRC): in the group receiving GAZYVARO plus bendamustine, median PFS was not yet reached; in the group receiving bendamustin PFS was 14.9 months, HR=0.55, 95 percent CI 0.40 – 0.74, p=0-0001).
• Investigator-assessed median PFS with the GAZYVARO regimen was more than double that with bendamustine alone (mPFS (investigator): GAZYVARO plus bendamustine 29.2 months vs. bendamustine alone 14 months, HR=0.52, 95 percent CI 0.39 – 0.70, p<0.0001).
• The GAZYVARO regimen reduced the risk of death (OS) by 38 percent (HR=0.62) compared to bendamustine alone based on a post hoc analysis eight months after the primary analysis. The median overall survival has not yet been reached in either study arm.³

About GAZYVARO (obinutuzumab)

GAZYVARO is an engineered monoclonal antibody designed to attach to CD20, a protein found on the surface of B-cells. GAZYVARO attacks and destroys these targeted cells both directly and together with the body's immune system. GAZYVARO is currently approved in more than 60 countries in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia. The approval was based on the CLL11 study, showing significant improvements with GAZYVARO plus chlorambucil across multiple clinical endpoints, including progression-free survival (PFS), overall response rate (ORR), complete response rate (CR) and minimal residual disease (MRD) when compared head-to-head with MabThera/rituximab plus chlorambucil.

Additional combination studies investigating GAZYVARO with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

About follicular lymphoma

Follicular lymphoma is the most common indolent (slow-growing) form of non-Hodgkin lymphoma (NHL), accounting for about one in five cases of NHL. It is considered incurable and relapse is common. It is estimated that more than 360 new cases of follicular lymphoma were diagnosed in Switzerland in 2015.⁴

About Roche in haematology

For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, Roche is investing more than ever in efforts to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera (rituximab) and GAZYVARO/Gazyva (obinutuzumab), Roche's pipeline of investigational haematology medicines includes an anti-PDL1 antibody (atezolizumab/MPDL3280A), 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 extends beyond oncology, with the development of the investigational haemophilia A treatment emicizumab (ACE910).

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. 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. 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.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. 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 seven years in a row by the Dow Jones Sustainability Indices.

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2015 employed more than 91,700 people worldwide. In 2015, Roche invested CHF 9.3 billion in R&D and posted sales of CHF 48.1 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.

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References

1 .Medicinal product information for GAZYVARO available at http://www.swissmedicinfo.ch
2. Sehn L et al. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. J Clin Oncol 2015. 33; ASCO 2015. Abstract LBA8502 and presentation.
3. http://www.gene.com/download/pdf/gazyva_prescribing.pdf (prescribing information for the USA, accessed on 27 April 2016).
4. Swiss Cancer League. Hodgkin and non-Hodgkin lymphoma: Lymph gland cancer – Information provided by the Cancer League for patients and people close to them. 3rd edition (2013) (in German). https://shop.krebsliga.ch/files/kls/webshop/PDFs/deutsch/lymphome-hodgkin-und-non-hodgkin-011080012111.pdf (accessed on 27 April 2016).