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
