Interim analysis of Phase 2 comparative study showed significant results in
favor of alemtuzumab versus Rebif(R)
CAMBRIDGE, Mass. and WAYNE, N.J., May 2 /PRNewswire-FirstCall/ --
Genzyme Corporation (Nasdaq: GENZ) and Bayer HealthCare Pharmaceutical
today announced detailed interim results from the CAMMS223 Phase 2 study.
This interim analysis of all patient data through at least twenty-four
months from the start of the study for all patients showed that a
once-yearly cycle of alemtuzumab treatment had a statistically significant
impact on reducing the frequency of relapses and the sustained accumulation
of disability in early active relapsing remitting multiple sclerosis (RRMS)
patients compared to Rebif(R) (interferon beta-1a).
The data were presented yesterday at the 59th Annual Meeting of the
American Academy of Neurology (AAN) in Boston by Dr. Alasdair J. Coles,
Ph.D., MRCP, Addenbrooke's Hospital, University of Cambridge, United
Kingdom. This is the first time that an analysis of the primary and
secondary endpoints has been presented in full.
Dr. Coles' presentation showed patients taking alemtuzumab at the high
dose experienced an 87 percent reduction in the risk for relapse (p<0.0001)
and a 66 percent reduction in the risk for progression of clinically
significant disability (p<0.0098) when compared to patients treated with
Rebif. At the low dose, patients taking alemtuzumab experienced similar
results, with a 72 percent reduction in the risk for relapse (p<0.0001) and
an 88 percent reduction in the risk for progression of clinically
significant disability (p<0.0008) compared with patients treated with
Rebif. Patients in both alemtuzumab arms also achieved a statistically
significant reduction in disability compared with their pre-treatment
baseline, as measured by their Extended Disability Status Scale (EDSS)
scores.
"Although several therapies are already available to treat MS, patients
still face an unmet need for more effective treatment that further
stabilizes disability," said Principal Investigator Professor D. Alastair
S. Compston, MBBS, Ph.D., FRCP, FMedSci, Addenbrooke's Hospital, University
of Cambridge, United Kingdom. "The large two-year reductions in the risk of
relapse and sustained accumulation of disability seen in these interim
results are impressive, and potentially very encouraging for the many
people worldwide who currently face an uncertain future with this
devastating disease and for their treating physicians."
As previously announced, dosing of alemtuzumab in this study was
voluntarily suspended in September 2005 after three cases of immune
thrombocytopenic purpura (ITP) were reported, the first of which resulted
in a fatality. The U.S. Food and Drug Administration (FDA) subsequently
placed the study on clinical hold. To date, six of the 216 (2.8 percent)
alemtuzumab- treated patients in the CAMMS223 study have developed ITP. ITP
is a disorder characterized by a low platelet count and corresponding
increased risk of uncontrolled bleeding. Though potentially serious, ITP
can be detected and monitored through blood tests, and is usually
treatable.
At the time of the dosing suspension, most patients had received two
cycles of therapy with alemtuzumab. Treatment with Rebif in the control arm
continued without interruption. Alemtuzumab re-dosing in the trial remains
on clinical hold in the United States, and active discussions are underway
with regulatory authorities regarding the clinical development program.
Significant progress has been made toward the initiation of two planned
Phase 3 clinical trials, one that will include previously untreated
patients and one that will involve patients receiving an approved therapy
whose disease remains active. These Phase 3 studies are expected to begin
this year, following FDA clearance. Alemtuzumab is an investigational drug
for the treatment of MS. Alemtuzumab should not be used in MS outside of
the formal clinical trial setting so that patient safety, including the
risk of ITP, can be monitored.
Phase 2 Study Details
The open-label, rater-blinded, randomized study enrolled 334 treatment-
naïve patients with early, active, RRMS. The trial compares the safety and
efficacy of alemtuzumab to Rebif. This is the first time that a potential
new therapy for multiple sclerosis has undergone a prospective, controlled,
multi- year, head-to-head comparison to a recommended first-line therapy.
In the trial, patients with RRMS at 49 medical centers in Europe and in
the U.S. were treated with alemtuzumab at one of two doses (12 or 24 mg IV
per day for five days at initial treatment, and for three days in the
subsequent yearly treatments), or Rebif (44 mcg administered subcutaneously
three times per week, as indicated in its product label). Although treating
physicians were aware of which treatment patients received, independent
(blinded) neurologists assessed the disability efficacy endpoint and
performed relapse evaluations.
Primary endpoints in the trial were the annualized relapse rate and the
time to Sustained Accumulation of Disability as measured by an increase in
EDSS scores lasting at least six months. The efficacy and safety data
analyses were reviewed by an independent Data and Safety Monitoring Board.
The final analysis of the primary endpoints in CAMMS223 will be based on
data through three years in all patients.
In addition to the results of the co-primary endpoints outlined above,
Dr. Coles presented the interim results of the change from baseline in MRI
T2 lesion volume and mean EDSS, which are secondary and tertiary endpoints,
respectively. Each of these findings supports the results seen in the
primary endpoints.
Safety Results
In the comparison of safety parameters of alemtuzumab vs. Rebif, a
greater number of serious adverse events (a subset of total adverse events)
were reported in patients receiving Rebif than in the two alemtuzumab dose
groups combined. Most of these were associated with patients who were
hospitalized for treatment of their MS.
The majority of adverse events (93 percent) in all three arms,
including infusion-associated adverse events, were mild-to-moderate in
intensity. The total number of adverse events was approximately twice as
high in each of the alemtuzumab-treated arms as in the Rebif-treated arm,
primarily due to the high number of infusion-associated adverse events.
Excluding infusion- associated adverse events (i.e., those occurring within
48 hours of an infusion), the incidence of adverse events was similar
across the three arms.
To date, a total of six of 216 (2.8 percent) alemtuzumab-treated
patients in the CAMMS223 study have developed ITP. In the initial case,
symptoms of ITP were experienced but not recognized in time to seek prompt
medical attention. After that case, the sponsor notified investigators and
patients of the risk of ITP, and a Patient Monitoring Program for ITP was
implemented in CAMMS223. The other five ITP patients were diagnosed
promptly, responded well to medical treatment, and have been stable without
ongoing treatment for ITP for between five and thirteen months. No new
cases of ITP have been reported in the study since September 2006. A
presentation of updated ITP information will be made at the AAN conference
by Herman Sullivan, MD on Wednesday, May 2, at 4:30PM EDT.
Additionally, the proportion of patients with thyroid-related clinical
adverse events after alemtuzumab treatment was 16.2 percent vs. 1.9 percent
after Rebif treatment. Thyroid adverse experiences were substantially less
common in the two years after alemtuzumab treatment than in prior studies
of the product in MS patients. A poster presentation of updated thyroid
autoimmunity information will be made by Dr. Coles on Thursday, May 3.
About Multiple Sclerosis
Multiple sclerosis is an immune-mediated disease of the central nervous
system (CNS) in which the immune system may attack the brain and spinal
cord. MS affects approximately 2.5 million people worldwide and
approximately twice as many women as men. The clinical course of MS is
highly variable, but is typically characterized by an initial relapsing and
remitting phase where episodes of transient neurological compromise are
followed by partial to full recovery. Within 10 to 20 years, however, most
patients experience progressive disability in which a steady worsening of
symptoms may culminate in profound muscle weakness, impaired gait and
mobility, bladder and bowel dysfunction, and cognitive and visual
impairments. At onset, relapsing- remitting MS is the most common form of
this disease.
About Alemtuzumab
Genzyme is conducting the clinical development program of alemtuzumab
in multiple sclerosis. Bayer HealthCare holds exclusive worldwide marketing
and distribution rights to alemtuzumab and participates with Genzyme in the
design of clinical protocols and conduct of activities for the development
of alemtuzumab for the treatment of MS. Alemtuzumab is an investigational
drug for the treatment of MS, and should not be used outside of the formal
clinical trial setting.
Alemtuzumab was approved in 2001 and is marketed outside the United
States as MabCampath(R) and in the U.S. by Bayer HealthCare Pharmaceuticals
Inc., as Campath(R). The product is indicated for the treatment of B-cell
chronic lymphocytic leukemia (B-CLL) in patients who have been treated with
alkylating agents and who have failed fludarabine therapy. Determination of
the effectiveness of Campath is based on overall response rates.
Comparative, randomized trials demonstrating increased survival or clinical
benefit such as improvement in disease-related symptoms have not yet been
conducted.
Alemtuzumab is a humanized monoclonal antibody that binds to a specific
target, CD52, on some cells of the immune system, including lymphocytes.
When alemtuzumab binds to these cells, it triggers their destruction by the
immune system. It is the first and only monoclonal antibody approved by the
FDA for the treatment of patients with B-cell Chronic Lymphocytic Leukemia
(B-CLL), a malignant disease of B-lymphocytes.
Campath should be administered under the supervision of a physician
experienced in the use of antineoplastic therapy. Campath has a boxed
warning which includes events of hematologic toxicity, infusion reactions,
and infections/opportunistic infections.
Campath is contraindicated in patients who have active systemic
infections, underlying immunodeficiency (e.g., seropositive for HIV), or
known Type 1 hypersensitivity or anaphylactic reactions to Campath or to
any one of its components.
The most commonly reported infusion-related adverse events in patients
with B-CLL were rigors, drug-related fever, nausea, vomiting, and
hypotension. Hematologic toxicities included pancytopenia/marrow
hypoplasia, anemia, thrombocytopenia, neutropenia, and profound
lymphopenia, and should be monitored. Infections reported included sepsis,
pneumonia, and opportunistic infections such as CMV, candidiasis,
aspergillosis, and mucormycosis.
Please refer to http://www.campath.com for complete prescribing
information of Campath in CLL.
About Genzyme
One of the world's leading biotechnology companies, Genzyme is
dedicated to making a major positive impact on the lives of people with
serious diseases. Since 1981, the company has grown from a small start-up
to a diversified enterprise with more than 9,000 employees in locations
spanning the globe and 2006 revenues of $3.2 billion. Genzyme has been
selected by FORTUNE as one of the "100 Best Companies to Work for" in the
United States.
With many established products and services helping patients in nearly
90 countries, Genzyme is a leader in the effort to develop and apply the
most advanced technologies in the life sciences. The company's products and
services are focused on rare inherited disorders, kidney disease,
orthopaedics, cancer, transplant and immune diseases, and diagnostic
testing. Genzyme's commitment to innovation continues today with a
substantial development program focused on these fields, as well as immune
disease, infectious disease, and other areas of unmet medical need.
About Bayer HealthCare
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals
unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world's
leading, innovative companies in the healthcare and medical products
industry, Bayer HealthCare combines the global activities of the Animal
Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the
US, Bayer HealthCare Pharmaceuticals comprises the following business
units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics,
Hematology/Cardiology and Oncology. The company's aim is to discover and
manufacture products that will improve human health worldwide by
diagnosing, preventing and treating diseases.
Forward-Looking Statements
This press release contains forward-looking statements, including
statements about clinical trial results, regulatory plans and expected
timelines for alemtuzumab, including the initiation of a Phase 3 trial in
MS patients and the timing thereof, and the ability to manage patient
safety. These statements are subject to risks and uncertainties that could
cause actual results to differ materially from those projected in these
forward- looking statements. These risks and uncertainties include, among
others: that final results of the clinical trial demonstrate safety and
efficacy comparable to the interim data that have emerged to date, the
actual timing and content of submissions to and decisions made by the
regulatory authorities, institutional review boards, data safety monitoring
boards and treating physicians regarding the continued administration of
alemtuzumab to MS patients, Genzyme's ability to develop and obtain
approval of a patient safety plan, and the other risks and uncertainties
described in reports filed by Genzyme with the Securities and Exchange
Commission. Please see the disclosure under the heading "Risk Factors" in
the Management's Discussion and Analysis of Genzyme Corporation and
Subsidiaries' Financial Condition and Results of Operations section of
Genzyme's Annual Report on Form 10-K for the year ended December 31, 2006
for a more complete discussion of these and other risks. Genzyme cautions
investors not to place substantial reliance on the forward- looking
statements contained in this press release. These statements speak only as
of the date of this press release, and Genzyme undertakes no obligation to
update or revise the statements.
This news release contains forward-looking statements based on current
assumptions and forecasts made by Bayer Group management. Various known and
unknown risks, uncertainties and other factors could lead to material
differences between the actual future results, financial situation,
development or performance of the company and the estimates given here.
These factors include those discussed in our public reports filed with the
Frankfurt Stock Exchange and with the U.S. Securities and Exchange
Commission (including Form 20-F). The company assumes no liability
whatsoever to update these forward-looking statements or to conform them to
future events or developments.
Genzyme(R), Campath(R), and MabCampath(R) are registered trademarks of
Genzyme Corporation. All rights reserved.
Rebif(R) is a registered trademark of EMD Serono, Inc.
Genzyme's press releases and other company information are available at
http://www.genzyme.com and by calling Genzyme's investor information line
at
1-800-905-4369 within the United States or 1-703-797-1866 outside the
United States.
Bayer HealthCare press releases and other information are available at
http://pharma.bayer.com or by calling 1-888-84BAYER
Genzyme Contacts: Bayer HealthCare Media Contacts:
Dan Quinn (media) Marcy Funk (US media)
(617) 768-6849 (973) 305-5385
Sally Curley (investors)
(617) 768-6140
SOURCE Genzyme Corporation
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Related links:
http://www.genzyme.com
http://www.campath.com http://pharma.bayer.com
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CONTACT:
Media, Dan Quinn, +1-617-768-6849, or
Investors, Sally Curley, +1-617-768-6140, both of Genzyme
Corporation; or Marcy Funk of Bayer HealthCare Media,
+1-973-305-5385
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