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BTG plc: Final Phase II Results of CampathR Multiple Sclerosis Study
Published
Results show a significant and sustained reduction in disability and
risk of relapse for MS patients on Campath® versus those on Rebif®
London, UK, 23 October 2008: BTG plc (LSE: BGC), the life sciences
company, notes the announcement by Genzyme Corporation and Bayer HealthCare
Pharmaceuticals Inc. of the publication in today’s edition of the New England
Journal of Medicine of the final results of the phase II trial of Campath® (alemtuzumab)
versus Rebif® (high-dose interferon beta-1a) in patients with early
relapsing-remitting multiple sclerosis. Patients taking once-yearly cycles of
Campath® reduced their risk of relapse by 74% and the risk of sustained
accumulation of disability by 71% compared to patients treated with the active
comparator, Rebif®.
Louise Makin, BTG’s chief executive officer, commented: “These results clearly
demonstrate the potential of Campath® to be a significant new treatment option
for people with multiple sclerosis and give us further confidence in the
prospects for the ongoing phase III pivotal trials.”
Campath® is currently approved for the treatment of B-cell chronic lymphocytic
leukaemia. BTG receives a royalty on worldwide sales in all indications for
which Campath® receives approval.
The full text of Genzyme’s announcement follows.
Study Results: Multiple Sclerosis Patients Have Significant and Sustained
Reduction in Disability and Risk Of Relapse On Alemtuzumab Versus Approved
Therapy, Rebif®
Final Phase 2 Data Published in New England Journal of Medicine
International Phase 3 Alemtuzumab Studies Enrolling
CAMBRIDGE, MA and WAYNE, NJ – Genzyme Corporation (Nasdaq: GENZ) and Bayer
HealthCare Pharmaceuticals Inc. today announced study results showing that
patients with early relapsing-remitting multiple sclerosis (RRMS) taking
once-yearly cycles of alemtuzumab reduced their risk of relapse by 74 percent
and the risk of sustained accumulation of disability by 71 percent compared to
patients treated with the active comparator Rebif® (high-dose interferon
beta-1a). Importantly, the mean disability of patients on alemtuzumab improved
from baseline, whereas the mean disability of those on Rebif worsened. The
treatment benefits of alemtuzumab were sustained for at least three years, even
though the majority of alemtuzumab-treated patients were last dosed two years
earlier. These results come from the final three-year analysis of a Phase 2
clinical study (CAMMS223) reported in the Oct. 23 issue of the New England
Journal of Medicine. The study involved 334 patients who had not previously been
treated for their disease.
“The alemtuzumab trial data continue to suggest a potentially new and exciting
treatment for patients with early, active multiple sclerosis,” says Alastair
Compston, Professor of Neurology and the head of the Department of Clinical
Neurosciences at the University of Cambridge, United Kingdom, and the study’s
principal investigator. “This randomized study confirms findings from prior
studies demonstrating that treatment with alemtuzumab can have a profound and
durable impact on patients with relapsing-remitting multiple sclerosis,
including restoring some lost function in many patients.”
“Symptoms of multiple sclerosis result from an immune system attack on the
protective insulation surrounding nerve fibers of the central nervous system. We
believe alemtuzumab shuts down this immune system attack, treating the disease
at its root cause,” says Alasdair Coles, Senior Lecturer, Department of Clinical
Neurosciences, University of Cambridge and a lead investigator in the study.
Common non-serious adverse events in the trial included infusion-associated
reactions in the alemtuzumab patients and flu-like symptoms in patients using
Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to
experience infections, which were predominantly mild to moderate in severity, as
well as autoimmune thyroid disease. Three percent of alemtuzumab-treated
patients developed the potentially serious autoimmune adverse event immune
thrombocytopenic purpura (ITP), a disorder characterized by a low platelet count
and corresponding increased risk of uncontrolled bleeding. Additional study and
trial safety information is below.
“The trial was larger and follow-up was longer than the typical Phase 2 trial in
multiple sclerosis. It is important to note that we compared the investigative
drug directly against a widely used therapy rather than against placebo. The
trial did not show an increased risk of life-threatening or opportunistic
infections, but a proportion of alemtuzumab patients experienced new autoimmune
disease. We have been able to create a robust patient monitoring program that
allows us to proceed into our two international Phase 3 trials with greater
assurance on safety associated with patient management,” says Dr. Richard
Moscicki, chief medical officer for Genzyme.
According to the National Multiple Sclerosis Society, approximately 400,000
Americans acknowledge having MS, and every week about 200 people are diagnosed.
Worldwide, multiple sclerosis may affect 2.5 million individuals. The disease
causes a wide range of symptoms including difficulty walking, numbness, fatigue
and impairment of vision, and progresses to permanent, severe disability in the
majority of patients. Relapsing-remitting MS is the most common presenting form
of the disease.
“We are pleased to see potential new treatment options move positively through
the MS pipeline,” says Dr. John Richert, executive vice president for research
and clinical programs at the National Multiple Sclerosis Society, “and as
alemtuzumab is moved into Phase 3 studies, we hope that individuals with MS will
consult with their physicians to assess whether they are appropriate patients
and if so will consider the pros and cons of participating in these important
clinical trials.”
Additional New Top-Line Data
New and previously unreported top-line data from secondary analyses of the
CAMMS223 Phase 2 clinical trial, presented last month at the World Congress on
Treatment and Research in Multiple Sclerosis (WCTRIMS), revealed that the
proportion of clinically disease-free patients was significantly higher in the
alemtuzumab group than in the Rebif group at year one (86 percent vs. 63
percent), year two (81 percent vs. 48 percent), and year three (71 percent vs.
39 percent, p-values <0.0001). “Clinically disease-free” was defined as the
absence of both relapses and sustained accumulation of disability during the
time-period assessed.
The top-line data from WCTRIMS also showed that the proportion of patients free
of sustained accumulation of disability over a six-month period was also
significantly greater in the alemtuzumab group than in the Rebif group at year
one (97.2 percent vs. 87.0 percent), year two (94.3 percent vs. 82.4 percent),
and year three (91.0 percent vs. 73.8 percent, p-values <0.005).
Further, the proportion of relapse-free patients over time was significantly
greater in the alemtuzumab group than in the Rebif group at year one (91.1
percent vs. 69.3 percent), year two (88.2 percent vs. 58.5), and year three
(80.2 percent vs. 51.6 percent, p-values <0.0001).
Phase 2 Extension Trial
Genzyme with Bayer support has launched an extension of the CAMMS223 trial to
examine safety and efficacy outcomes beyond three years, and to compare two
distinct retreatment strategies. The results should provide an understanding of
the long-term effects of prior alemtuzumab treatment as well as the safety and
sustained efficacy of additional alemtuzumab retreatment delivered in fixed
annual cycles or as needed for resumed MS disease activity. In the fixed arm,
patients will receive two annual cycles of alemtuzumab (12 mg/day for three
consecutive days/cycle). In the as-needed arm, retreatment is deferred until a
patient relapses or develops two or more new/active brain lesions on MRI.
Phase 3 Trials
Genzyme with Bayer support is sponsoring two Phase 3 trials in which patients
are now enrolling. The CARE-MS I Phase 3 study (Comparison of Alemtuzumab and
Rebif Efficacy in Multiple Sclerosis), is a randomized, rater-blinded study that
will again compare alemtuzumab to Rebif in patients with relapsing-remitting MS
who have not been previously treated for their disease. The CARE-MS II trial is
studying patients who have continued to relapse while using approved MS
therapies.
Physicians or patients in the United States seeking additional information about
the CARE-MS Phase 3 trials should call Genzyme Medical Information at
800-745-4447.
About Study CAMMS223
In the Phase 2 trial, 334 patients with active relapsing-remitting multiple
sclerosis were enrolled at 49 medical centers in Europe and the United States.
Patients in the trial were randomized to treatment with alemtuzumab at one of
two dose levels (12 or 24 mg per day intravenously) for five days during the
first cycle and three days 12 months later during the second cycle of therapy,
or Rebif (44 mcg administered by subcutaneous injection three times per week, as
indicated in its product label). A third cycle of alemtuzumab therapy was
received by 46 patients at month 24.
The trial compared the efficacy of alemtuzumab with Rebif using two primary
outcome measures: the Relapse Rate and the time to Sustained Accumulation of
Disability as evidenced by an increase in the Expanded Disability Status Scale (EDSS)
score for six consecutive months. Efficacy assessments were made by independent
neurologists blinded to patients’ treatment assignments. The EDSS is a 10-point
scale in which every 0.5-point step marks a notable deterioration in
neurological capabilities.
The mean disability score of patients after alemtuzumab actually improved (by
0.39 EDSS points) indicating a recovery of neurologic functions. The median
disability score improved to a similar extent after alemtuzumab. In contrast,
mean disability worsened in the Rebif group (by 0.38 EDSS points) resulting in a
difference of nearly a full EDSS point (0.77 difference, p<0.0001) at three
years.
Safety Data
A total of six alemtuzumab-treated patients, and one Rebif-treated patient, in
this study developed a serious adverse event, immune thrombocytopenic purpura (ITP).
ITP is a disorder characterized by a low platelet count and corresponding
increased risk of uncontrolled bleeding. The Rebif patient with ITP was
asymptomatic but ITP persisted at the time of study completion. In the
previously reported alemtuzumab-related fatal case, symptoms of ITP were
experienced but were not recognized in time, thus delaying medical attention. Of
the remaining alemtuzumab cases, four patients were diagnosed promptly,
responded well to medical treatment, and have been stable without a need for
ongoing treatment. The other alemtuzumab-treated case experienced spontaneous
remission of ITP. A patient monitoring program was instituted in the trial, and
there have been no new cases of ITP reported in CAMMS223 in approximately two
years.
Common non-serious adverse events in the trial included infusion-associated
reactions in the alemtuzumab patients and flu-like symptoms in patients using
Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to
experience infections, particularly of the upper respiratory tract; infections
were predominantly mild to moderate in severity and there were no
life-threatening or fatal infections. Though alemtuzumab transiently lowers
white blood cell counts, the trial did not show an increased risk of
opportunistic infections. Serious infections were infrequent in the alemtuzumab-treated
patients. Approximately 23 percent of alemtuzumab-treated patients developed
autoimmune thyroid-related adverse events, including Graves’ disease, and were
managed using conventional therapies.
Alemtuzumab is an investigational drug for the treatment of MS and must not be
used in MS patients outside of a formal, regulated clinical trial setting in
which appropriate patient monitoring measures are in place.
About Alemtuzumab
Alemtuzumab is licensed in the United States as a single agent for the treatment
of B-cell chronic lymphocytic leukemia (B-CLL), and outside of the U.S. for the
treatment of B-CLL in patients who have been treated with alkylating agents and
for whom fludarabine combination therapy is not appropriate. The product was
launched in its oncology indication in 2001 in the US, where it is marketed by
Bayer HealthCare Pharmaceuticals Inc. as Campath®, and in Europe, where it is
named MabCampath®.
Alemtuzumab is a humanized monoclonal antibody that binds to a specific target,
CD52, on cell surfaces and directs the body’s immune system to destroy those
cells. It is the first and only monoclonal antibody approved by the FDA for the
treatment of patients with B-CLL.
Genzyme and Bayer are co-developing alemtuzumab in oncology and multiple
sclerosis. Bayer holds exclusive worldwide marketing and distribution rights to
alemtuzumab.
Campath for B-CLL has a boxed warning that includes information on cytopenias,
infusion reactions, and infections. The most commonly reported adverse reactions
in patients with B-CLL were infusion reactions (fever, chills, hypotension,
urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia,
lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV
infection, other infections). Other commonly reported adverse reactions include
vomiting, abdominal pain, insomnia and anxiety. The most commonly reported
serious adverse reactions are cytopenias, infusion reactions, and
immunosuppression/infections.
For further information contact:
BTG
Andy Burrows, Director of Investor Relations
+44 (0)20 7575 1741; mobile: +44 (0)7990 530605
Christine Soden, Chief Financial Officer
+44 (0)20 7575 1591
Financial Dynamics
Ben Atwell
+44 (0)20 7831 3113
About BTG
BTG in-licenses, develops and commercialises pharmaceuticals and has a broad
pipeline of development programmes targeting neurological and other disorders
including varicose veins. The company also has a substantial and growing revenue
stream of milestone payments and royalties from out-licensed products. BTG
operates from offices in London, Philadelphia and Osaka. For further
information, visit: www.btgplc.com .
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