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Roche Provides Update on Leading Late-Stage Pharmaceutical Pipeline

New data on medicines with the potential to redefine standard of care highlighted at Investor event

Basel and London, 9 December 2010Roche (SIX: RO, ROG; OTCQX: RHHBY) today will provide an update on its leading late-stage pipeline comprising twelve new molecular entities in key therapeutic areas. The London investor event will focus on major progress that has been achieved in recent months with Roche’s late-stage pipeline assets in the areas of oncology and CNS, as well as on further development plans of these potential breakthrough medicines.

“Our goal is to continue delivering innovative medicines in therapeutic areas of high unmet need and to bring true medical value to patients. I am pleased that the glycine reuptake inhibitor and ocrelizumab - two molecules with the potential to treat severe diseases such as schizophrenia or multiple sclerosis are progressing to late-stage development”, said Hal Barron, M.D., Head of Global Product Development and Chief Medical Officer of Roche. “We also see that the concept of Personalized Healthcare is becoming a reality for more and more of our development projects. MetMAb and the BRAF inhibitor are two encouraging examples for how personalized therapy could improve outcomes in lung cancer and melanoma, respectively.”

Roche’s late-stage pipeline is progressing well with potentially ten regulatory submissions of new molecular entities until the end of 2013. Pipeline molecules such as T-DM1 and pertuzumab in breast cancer, GA101/RG7159 in NHL1 and CLL2 or the BRAF inhibitor RG7204 in melanoma are designed to move the standard of care in treating these diseases and improve the chances of longer survival or even cure. Other molecules such as the glycine reuptake inhibitor RG1678 and ocrelizumab RG1594 have the potential to improve outcomes in diseases such as schizophrenia or multiple sclerosis where new therapies are urgently needed.

Start of phase III programs for potential breakthrough therapies in schizophrenia and multiple sclerosis

Schizophrenia
Positive phase II proof-of-concept data with RG1678 in patients with predominantly negative symptoms of schizophrenia were recently presented at an international medical meeting3. Based on these promising results, a global phase III program has been initiated which includes a total of six studies investigating RG1678 in combination with standard of care antipsychotic drugs in patients with either negative symptoms4 or residual positive symptoms of schizophrenia5. Running the studies for both indications in parallel will allow a better understanding of the effect of RG1678 on a broad spectrum of symptoms and its value in the management of patients at different phases of their disease. The first patient was randomized into the phase III program in November 2010.

RG1678 is an investigational first-in-class glycine reuptake inhibitor that normalizes glutamate neurotransmission, thereby targeting an important pathway in the treatment of psychiatric disorders. By normalising glutamate neurotransmission in the brain, RG1678’s unique mode of action could also have valuable therapeutic applications in other psychiatric indications beyond schizophrenia.

Multiple sclerosis
Ocrelizumab, a humanized anti-CD20 antibody administered as a six-monthly infusion, demonstrated a highly significant reduction in disease activity as measured by brain lesions (96% for 2000mg and 89% for 600mg ocrelizumab dosing regimens) and relapse rate (73% for 2000mg and 80% for 600mg ocrelizumab at week 24) compared to placebo in a phase II study in relapsing-remitting multiple sclerosis (RRMS). The efficacy data, amongst the highest seen in a phase II RRMS study, were recently reported at the ECTRIMS conference. Based on these results, ocrelizumab will move into phase III studies in multiple sclerosis. Two studies will explore ocrelizumab’s efficacy in RRMS head-to-head versus interferon, the current standard of care, and one study will investigate the potential of ocrelizumab in patients with primary-progressive multiple sclerosis (PPMS). Phase III studies for ocrelizumab will commence in the first quarter of 2011.

Improved chances of survival or cure for cancer patients in most common cancer indications

HER2-positive breast cancer:
New pertuzumab-Herceptin (trastuzumab) data from the randomized phase II Neosphere study in neoadjuvant HER2-positive breast cancer will be presented at SABCS. Pertuzumab and trastuzumab are synergistic and their combination enhances the blockade of HER2-signalling pathways. Therefore, combining the two antibodies may improve the clinical benefit for women with HER2-positive breast cancer. Encouraged by the efficacy results from Neosphere, pertuzumab will also be studied in early (adjuvant) HER2-positive breast cancer. The phase III clinical program in this setting will start in 2011. Data from the phase III study in 1st line HER2-positive metastatic breast cancer CLEOPATRA are expected for 2011. Phase II data for the antibody-drug conjugate T-DM1 (trastuzumab-DM1) in 1st line HER2-positive breast cancer presented at ESMO in October 2010 demonstrated that it may soon be possible to treat HER2-positive breast cancer without conventional chemotherapy with the potential to significantly reduce side-effects of therapy. T-DM1 single agent showed comparable efficacy to Herceptin plus docetaxel (objective response rate 47.8% vs. 41.4%, p=0.456) but with a much better safety profile. For patients treated with T-DM1, the incidence of serious adverse events grade 3 or higher was reduced by half compared to those taking Herceptin + docetaxel (37% vs 75%), a benefit resulting from the reduced systemic chemotherapy exposure. Final results from this study are expected in Q2 2011. Two phase III studies in 1st and 2nd line HER2-positive metastatic breast cancer, MARIANNE and EMILIA are also ongoing. Lung cancer:
Promising early results from a phase II study in 2nd/3rd line non-small cell lung cancer (NSCLC) with MetMAb, a unique monovalent antibody, were reported at ESMO in October 2010. Patients with NSCLC who overexpress MET lived almost twice as long without their disease getting worse (progression-free survival) when treated with MetMab plus Tarceva compared to placebo plus Tarceva (HR=0.560, p=0.0547). Final data from the study are expected to be presented at an upcoming medical meeting. A phase III study in 2nd/3rd line NSCLC patients with high MET expression is expected to start in 2011. MetMAb is also being studied in combination with a paclitaxel regimen with or without Avastin in a phase II study in 1st and 2nd line triple negative metastatic breast cancer with enrollment expected to start in Q1 2011.

Metastatic melanoma:
Data from the phase II study BRIM-2 evaluating RG7204 in patients with previously treated BRAF mutation-positive metastatic melanoma were presented at the International Melanoma Congress of the Society for Melanoma Research in November 2010. RG7204 is a targeted inhibitor of the cancer-causing mutant BRAF protein which is present in more than half of the malignant melanomas. In the study, treatment with RG7204 resulted in a progression-free survival (the time patients could live without the disease getting worse) of 6.2 months. Tumor shrinkage (objective response rate) occurred in 52% percent of patients. Data from a phase III study in previously untreated BRAF mutation-positive metastatic melanoma patients (BRIM-3) are expected in 2011.

Non-Hodgkin’s lymphoma
Promising early efficacy data were recently reported at ASH from a phase II study with GA101/RG7159, the first glyco-engineered type II humanized anti-CD20 monoclonal antibody in relapsed/refractory aggressive non-Hodgkin’s lymphoma (NHL). Patients in this study had received a median of three prior therapies and 63% of patients were not responsive to or relapsed within six months of treatment with MabThera/Rituxan. Nearly a third of patients responded to treatment with RG7159 (end of treatment response 28% all patients; 24% in the low-dose cohort, 32% in the high-dose cohort).

Also at ASH, an update of encouraging efficacy data from a phase II study in patients with relapsed/refractory indolent NHL were presented. Patients in this study had received a median of 3 prior therapies and 50% were not responsive to or relapsed within six months of therapy with MabThera/Rituxan. Patients were randomized to two doses of GA101/RG7159. Efficacy in the higher dose cohort was superior with objective response rate of 55% and median progression-free survival of 11.3 months in the overall patient group as well as in the group of patients not responding to MabThera/Rituxan anymore.

Two phase III studies comparing head-to-head MabThera/Rituxan and GA101/RG7159 in combination with chemotherapy, in both, indolent and diffuse large B-cell lymphoma are planned to start in 2011.

The collaboration of Roche’s Pharmaceuticals and Diagnostics Divisions allows for an integrated effort to progress Personalised Healthcare, leveraging advances in science to develop novel medicines in conjunction with predictive diagnostic tests. In oncology, biomarker programs for all phase III projects are in development. These programs include biomarker assays for the BRAF inhibitor, pertuzumab, T-DM1 and MetMAb.

Overview on 14 new molecular entities in ongoing or planned late-stage studies Compound Indication Status
aleglitazar Cardiovascular high risk in type 2 diabetes Phase III initiated in Q1 2010
BRAF inhibitor RG7204 Metastatic melanoma, 2nd / 3rd line Pivotal phase II data at IMC 2010
dalcetrapib Dyslipidemia, cardiovascular risk reduction Phase III enrolment completed Q2 2010
GA101 / RG7159 Non-Hodgkin’s lymphoma and chronic lymphocytic leukemia Phase III started Q4 2009 (chronic lymphocytic leukemia)
Glycine Reuptake Inhibitor (GRI) RG1678 Negative symptoms and sub-optimally controlled positive symptoms of schizophrenia Phase III started in Nov 2010
Hedgehog pathway inhibitor RG3616 Advanced basal cell carcinoma Pivotal phase II started Q1 2009
HCV polymerase inhibitor RG7128 Hepatitis C LIP decision made, phase III decision pending
lebrikizumab Asthma LIP and phase III decision pending
MetMAb Solid cancers LIP decision made, phase III in preparation
ocrelizumab Multiple sclerosis (RRMS and PPMS) Phase III to start in Q1 2011 (PPMS) and Q2 2011 (RRMS)
pertuzumab HER2-positive metastatic breast cancer, 1st line Phase III started in 2008
SGLT2 inhibitor RG7201 Type-2 diabetes LIP and phase III decision pending
taspoglutide Type-2 diabetes Dosing stopped in phase III program, next steps to be communicated
trastuzumab–DM1 HER2-positive metastatic breast cancer, 2nd line Phase III started Q1 2009

LIP= Life Cycle Investment Point

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 2009, Roche had over 80’000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 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.

All trademarks used or mentioned in this release are protected by law.

1 Non-Hodgkin’s lymphoma
2 Chronic lymphocytic leukaemia
3 ‘Glycine Transporter Type 1 (GLYT1) Inhibitor RG1678: Positive Results Of The Proof-Of-Concept Study For The Treatment Of Negative Symptoms In Schizophrenia’, Umbricht D. et al., ACNP 2010
4 more than 50% of patients with schizophrenia suffer from significant negative symptoms which include disruption to normal behavior and emotion, such as a lack of ability to sustain planned activity or a lack of pleasure in everyday life
5 most patients on existing antipsychotic therapies suffer from residual positive symptoms which include psychotic behaviors not seen in healthy people, such as hallucinations and delusions that have a negative impact on their functionality and increase the risk of a relapse requiring treatment in hospital
 

Posted: December 2010


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