Investor Update

Basel, 12 December 2011

First head to head study shows higher response rates for GA101 vs. MabThera/Rituxan without appreciable differences in safety in common type of blood cancer

Separate study indicates that GA101 is highly effective in combination with chemotherapy

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that its investigational unique type II anti-CD20 antibody GA101 (obinutuzumab) increased the overall response rate (ORR) of patients with relapsed CD20+ indolent non-Hodgkin’s Lymphoma (iNHL), a common type of blood cancer, compared to MabThera/Rituxan (rituximab) in the first head to head comparison. The data come from two separate studies and were presented at the 53rd annual meeting of the American Society of Hematology (ASH):

  • The randomized Phase II study known as GAUSS is the first head to head comparison of GA101 and MabThera/Rituxan and showed an increase in ORR favouring GA101 over MabThera/Rituxan. It also showed that there were no new safety concerns for GA101 and that the safety profile was similar between the two treatment arms.
  • In the Phase Ib study called GAUDI the study investigators concluded that GA101 is highly effective in combination with chemotherapy in patients with relapsed/refractory follicular lymphoma without new safety concerns.

Both studies supported the decision to move into a phase III program with GA101 in NHL patients.

"This is the first time GA101, a novel anti-CD20 antibody, has been compared to MabThera/Rituxan,” said Hal Barron M.D., Chief Medical Officer and Head, Global Product Development. “Our goal with the GA101 program is to demonstrate superior efficacy and comparable tolerability to MabThera/Rituxan. This ambitious target reflects our commitment to further improve outcomes for patients with blood cancers.”

The GAUSS study randomised 175 patients with relapsed indolent non-Hodgkin’s lymphoma (iNHL) to receive either single agent GA101 or single agent MabThera/Rituxan. The primary objective of the study was an improvement in ORR, as assessed by the investigator, in the subgroup of 149 patients with follicular lymphoma (FL).

  • The analysis in this group of patients showed an increase in ORR for GA101 relative to MabThera/Rituxan of ~11% (45% vs. 33%).
  • Importantly, a central blinded and independent radiology review (IRF) was performed to assess response which demonstrated a greater difference in ORR of ~18% (45% vs. 27%) favouring GA101 in FL patients.
  • The time until the disease worsened (progression-free survival - PFS) was similar between treatment arms at this early time point.
  • The study also showed that the tolerability profiles of GA101 and MabThera/Rituxan were comparable, with no new safety concerns for GA101. There was a slight increase in the proportion of patients with infusion-related reactions (IRRs) in the GA101 arm compared to MabThera/Rituxan, but this did not result in differences in treatment discontinuation.

At ASH data was also presented from the GAUDI study which indicated that GA101 is highly effective in combination with chemotherapy in relapsed / refractory follicular lymphoma patients. In GAUDI, high response rates of 93% and 96% were recorded when GA101 was combined with FC and CHOP respectively. These outcomes compare favourably with historical controls. There were no new safety concerns and adverse events were consistent with those seen in previous studies of GA101.

Based on the positive outcomes from GAUSS and GAUDI, two large Phase III trials (GALLIUM and GOYA) have been initiated comparing GA101 plus chemotherapy versus MabThera/Rituxan plus chemotherapy in previously untreated patients with iNHL and diffuse large B-cell lymphoma (DLBCL). The GA101 development program also includes two additional Phase III trials evaluating this new antibody in previously untreated patients with chronic lymphocytic leukemia (CLL11) and in iNHL patients who no longer respond to treatment with MabThera/Rituxan (GADOLIN). The goal of the front-line studies is to demonstrate that GA101 provides improved efficacy outcomes without new safety concerns for patients compared to MabThera/Rituxan based therapies.

About hematological malignancies

The hematological malignancies or blood cancers that GA101 is designed to treat include chronic lymphocytic leukemia (CLL) and different types of non-Hodgkin’s lymphoma (NHL), including indolent lymphoma and diffuse large B-cell lymphoma (DLBCL).  By 2015, it is expected that there will be nearly 225,000 annual deaths worldwide from non-Hodgkin’s lymphoma , and nearly 250,000 from leukemia .  The current standard of care in CD20+ hematological malignancies is MabThera/Rituxan in combination with chemotherapy or as single agent.

About GAUSS

GAUSS is the first head to head study of MabThera/Rituxan compared with another anti-CD20 antibody, in this case GA101, reporting results. A total of 175 patients with relapsed CD20+ iNHL (149 with follicular lymphoma and 26 with non-follicular NHL) were randomised at a ratio of 1:1 to receive 4 weekly infusions on days 1, 8, 15 and 22 of either GA101 (1,000 mg) or MabThera/Rituxan (375 mg/m2) as a monotherapy.  The primary endpoint for the Phase II part of the study was overall response rate as assessed by investigators in the subset of patients with follicular lymphoma. Secondary endpoints include ORR in the overall population, progression-free survival, safety evaluation, and pharmacokinetic profile.

About GAUDI

GAUDI is a Phase Ib open-label, multi-center study designed to assess the safety and efficacy of GA101 given in combination with chemotherapy in patients with CD20+ follicular NHL. The primary objective of the study was safety, with efficacy as measured by response rate as a key secondary objective. The study included patients with relapsed or refractory disease (n=56) and previously untreated (first-line) patients (n=80). At ASH 2011, data from patients with relapsed or refractory disease was presented (see above). The GAUDI study is ongoing and data from previously untreated patients will be submitted for presentation at a future medical conference when available.

About GA101

GA101 is the first glycoengineered, type II, humanized anti-CD20 monoclonal antibody in development for the treatment of B-cell malignancies such as non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). GA101 has a distinct mode of action compared with other anti-CD20s, including MabThera/Rituxan, and was specifically designed to selectively target the CD20 protein on malignant B-cells and to bind with high affinity to the cell surface in a type II configuration. This maximizes direct cell death induction and antibody-dependent cytotoxicity (ADCC), leading to improved clinical efficacy. The full efficacy and safety profile of GA101 is being fully assessed in a large Phase III clinical development program which includes four studies assessing GA101 in previously untreated patients with CLL, aggressive NHL, indolent NHL and relapsed/refractory indolent NHL patients. To date, GA101 has provided positive signals of efficacy in clinical trials, with the GAUSS study achieving superior response rates to MabThera/Rituxan in a head to head comparison. Whilst MabThera/Rituxan has revolutionized the treatment of CD20-positive hematological malignancies, it is hoped that GA101 will surpass this and further improve the outcome of patients suffering from CD20+ B-cell malignancies.

About MabThera/Rituxan

MabThera/Rituxan is a type I therapeutic 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.

MabThera/Rituxan, discovered by Biogen Idec, first received FDA approval in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent. It was approved in the EU under the trade name MabThera in June 1998. Over 2.1 million patient exposures with MabThera/Rituxan have been recorded worldwide since launch, 2.0 million in hematological malignancies.

MabThera is known as Rituxan in the United States, Japan and Canada. Genentech and Biogen Idec 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 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, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2010, Roche had over 80’000 employees worldwide and invested over 9 billion Swiss francs in R&D. The Group posted sales of 47.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

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