Posted Wednesday, October 26, 2011
News from Genentech
– Phase III Trials Underway to Investigate Ocrelizumab in Two Forms of MS –
SOUTH SAN FRANCISCO, Calif. – October 19, 2011 – Genentech, a member of the
Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced 96-week results1
from a Phase II study of ocrelizumab in patients with relapsing-remitting multiple
sclerosis (RRMS), the most common clinical form2 of the disease. The study showed
that the significant reduction in disease activity as measured by the total number of
active brain lesions and relapses, previously reported for 24 weeks, was maintained
through 96 weeks. The data is being presented at ECTRIMS (European Committee for
Treatment and Research in Multiple Sclerosis), the world's largest annual international
conference devoted to basic and clinical research in multiple sclerosis.
People with RRMS suffer from relapses and disabling symptoms caused by
damage to the central nervous system (the brain, spinal cord and optic nerves) which
can significantly affect their quality of life. Symptoms are unpredictable and vary
between patients. Most people experience their first symptoms between the ages of 20
Results from the trial showed that during the 24-96 week treatment period, no
patient who received a dose of 600mg ocrelizumab developed a new or enlarging brain
lesion (as measured by MRI). The annualized relapse rate (ARR), the rate of clinical
attacks or flare-ups per patient-year, was less than 0.2 attacks per patient per year
across the 96-week period. The data also showed that, of the patients who completed
the study, two-thirds of the patients in the 600mg group were free of any disease activity
(as measured by MRI, relapses or neurological progression) over the 96-week treatment
"This demonstration of the long-term efficacy of ocrelizumab confirms the
compelling benefit demonstrated in the first 24-week treatment period,” said Hal Barron,
M.D., chief medical officer and head, Global Product Development. “These results
indicate a high likelihood of success of the ongoing Phase III program in patients with
relapsing-remitting multiple sclerosis. Additionally, a study is underway to evaluate the
potential benefit of ocrelizumab in patients with primary progressive multiple sclerosis.”
The safety profile of ocrelizumab over the 96 weeks of the study was consistent
with that demonstrated in the earlier 24-week data. No opportunistic infections were
reported and the rate of infections (and serious infections) did not increase over the
treatment period. Serious infection rates were similar for ocrelizumab 600mg (1.97
events/100 patient/years) and ocrelizumab 1000mg (1.93 events/100 patient/years) and
did not increase with time on ocrelizumab treatment.
About the Study
• A Phase II, randomized, multicenter, placebo-controlled study in 220 patients with
• A randomized, open-label, rater-blinded, interferon beta-1a (30mcg IM weekly) group
was enrolled as an active comparator arm.
• In the primary analysis, the efficacy and safety profile of the two dose regimens of
ocrelizumab were evaluated over 24 weeks versus placebo.
• At day one and day 15, patients either received intravenous infusions of 300mg
ocrelizumab, 1000mg ocrelizumab or placebo. An additional group received openlabel
interferon beta-1a (30mcg IM weekly).
• As reported previously, the total number of gadolinium-enhancing T1 lesions (based
on MRI scans at weeks 12, 16, 20 and 24) was significantly decreased by 89
percent in the 2 x 300mg arm and 92 percent in the 2 x 1000mg arm, compared to
both placebo and interferon beta-1a (p < 0.0001 for both doses).
• ARR was significantly reduced by 80 percent (p = 0.0005) with ocrelizumab 2 x
300mg and by 73 percent (p = 0.0014) with ocrelizumab 2 x 1000mg versus placebo
at week 24.
• At 24 weeks, in the double-blinded treatment groups (ocrelizumab 600mg,
ocrelizumab 2000mg vs. placebo) serious adverse events (SAEs) included: systemic
inflammatory response syndrome (SIRS) (0.0 percent, 1.8 percent vs. 0.0 percent),
hypersensitivity (1.8 percent, 0.0 percent vs. 0.0 percent), oral herpes (0.0 percent,
0.0 percent vs. 1.9 percent), squamous cell carcinoma of the skin (pre-existing
lesion) (0.0 percent, 1.8 percent vs. 0.0 percent) and anxiety (0.0 percent, 1.8
percent vs. 0.0 percent).
• At week 24 patients on placebo and interferon beta-1a were switched to
ocrelizumab, given as 2 x 300mg infusions through week 48 and single 600mg
infusions through week 96.
• Patients who began on 2 x 300mg and 2 x 1000mg ocrelizumab continued on
600mg or 1000mg, given as single infusions, until week 72, at which time patients
were switched to single 600mg infusions through to week 96.
• All groups were treated in open-label fashion after week 24.
• Overall, at week 96, there were no gadolinium-enhancing T1 lesions observed by
MRI scans of the brain in any patient in either of the ocrelizumab 600mg or 1000mg
• No new and/or enlarging T2 lesions were observed from weeks 24 to 96 in any
patient in the ocrelizumab 600mg group.
• The ARR for weeks 0-96 was 0.18 (95 percent CI: 0.11-0.31) for the ocrelizumab
600mg group and 0.22 (0.13-0.35) for the ocrelizumab 1000mg group.
• Overall, 67.3 percent of patients in the ocrelizumab 600mg group and 76.4 percent
of patients in the ocrelizumab 1000mg group had no relapses and no confirmed
EDSS (Expanded Disability Status Scale) progression from week 0-96 (“clinical
disease activity free”); 78.2 percent and 80.0 percent of patients, respectively, were
• There was no imbalance in the total number of SAEs observed across the treatment
groups to week 96.
• As has been previously reported, one death occurred in a patient receiving
ocrelizumab 2 x 1000mg, at week 14, secondary to a complicated course of
systemic inflammatory response syndrome.
• Serious infection rates were similar for ocrelizumab 600mg (1.97 events/100
patient/years [95 percent CI: 0.49-7.98]) and ocrelizumab 1000mg (1.93 events/100
patient/years [95 percent CI: 0.48-7.71]) and did not increase with time on
• No opportunistic infections were reported and the rate of infections (and serious
infections) did not increase over the treatment period.
About the Phase III Clinical Program
The ocrelizumab Phase III clinical program (Orchestra) consists of two studies in
patients with RRMS (Opera I and II) and one study in patients with primary progressive
multiple sclerosis (PPMS) (Oratorio). The program has now begun enrolling patients into
all of its trials. There is no approved therapy to treat PPMS, a much rarer form of the
disease, affecting about 10 percent of those with MS.
Ocrelizumab is an investigational, humanized monoclonal antibody designed to
selectively target CD20-positive B-cells, which are believed to play a critical role in
multiple sclerosis (MS). It then interacts with the body?s immune system to eliminate
About Multiple Sclerosis
Multiple sclerosis (MS) is a highly debilitating, autoimmune-mediated disease of the
central nervous system (CNS) and is one of the leading causes of neurological disability
in young adults3,4. The immune system incorrectly attacks healthy nerve tissue in the
CNS which affects the transfer of messages from the CNS to the rest of the body.
Symptoms are unpredictable and vary between patients, but include tingling, numbness,
pain, slurred speech and blurred or double vision. Some patients may experience
muscle weakness, poor balance or coordination and tremors as well as altered
sensation, memory and concentration problems. Over time (without treatment) most
patients develop permanent disability, including partial or complete paralysis and
difficulties with vision, speech and memory. According to estimates of the World Health
Organization, approximately 1.3 million people worldwide have been diagnosed with
MS6. Most people experience their first symptoms between the ages of 20 and 40
years7. Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical form
of MS and accounts for around 85 percent of all cases at onset2. RRMS is characterized
by infrequent, acute exacerbations with full or partial recovery between attacks.
Founded more than 30 years ago, Genentech is a leading biotechnology company that
discovers, develops, manufactures and commercializes medicines to treat patients with
serious or life-threatening medical conditions. The company, a member of the Roche
Group, has headquarters in South San Francisco, California.
For additional information about the company, please visit http://www.gene.com.
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