- Chronic constipation and IBS-C studies each meet primary endpoint -
CAMBRIDGE, MASS. and NEW YORK, March 4 /PRNewswire-FirstCall/ --
Microbia, Inc. and Forest Laboratories, Inc. (NYSE: FRX) today announced
positive top-line results from two Phase 2b randomized, double-blind,
placebo-controlled studies assessing the safety, therapeutic effect, and
dose response of four different once-daily doses of linaclotide: 75 mcg,
150 mcg, 300 mcg, and 600 mcg. The first study examined the effects of
linaclotide in patients with chronic constipation (CC), while the second
study examined its effects in patients with irritable bowel syndrome with
constipation (IBS-C). Preliminary analysis of the CC study data and an
interim analysis of the IBS-C study data indicate that each study met its
primary endpoint.
(Logo: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO )
In the four-week CC study, the primary efficacy endpoint was the change
from pre-treatment in weekly spontaneous bowel movement (SBM) frequency
rate. During the two-week pre-treatment period, the mean baseline weekly
SBM frequency rate across all treatment groups was 2.31. Patients who
received once-daily dosing of linaclotide demonstrated a dose-responsive
increase in weekly SBM frequency rate ranging from 0.98 (75 mcg, p = 0.09)
to 2.99 (600 mcg, p < 0.0001) compared to patients receiving placebo. The
response was significant at all doses above 75 mcg. Linaclotide-treated
patients also experienced improvements in all other top-line efficacy
endpoints-complete spontaneous bowel movement (CSBM) frequency, stool
consistency, straining, abdominal pain, bloating, and abdominal
discomfort-that were statistically significant for at least two of the four
linaclotide dose groups for each endpoint. Linaclotide was well tolerated
at all doses with no serious adverse events in any patient during the
treatment period. The most common adverse event was diarrhea, which was
dose-related and ranged from 4.8 percent to 14.3 percent in the
linaclotide-treated patients compared to 2.9 percent of placebo-treated
patients. Diarrhea resulted in discontinuation of 2.5 percent of
linaclotide-treated patients and no placebo-treated patients. At this time
the companies have reviewed only top-line results and further analyses will
be conducted in the coming weeks.
An interim analysis of the recently completed 12-week IBS-C study was
carried out to enable timely dose selection for Phase 3 trials. The interim
analysis was performed on the unlocked database for this study, following
the last patient's last visit. Patients with IBS-C who received once-daily
treatment with linaclotide experienced a significant increase in weekly
CSBM frequency rate-the primary endpoint for this study-at all doses except
for 150 mcg. Linaclotide-treated patients also experienced improvements in
all other top-line efficacy endpoints-SBM frequency, stool consistency,
abdominal pain, bloating, abdominal discomfort, adequate relief, and IBS-C
symptom severity-that were statistically significant for at least two of
the four linaclotide dose groups for each endpoint. Linaclotide was well
tolerated at all doses; there was one serious adverse event in a
linaclotide-treated patient which was considered unrelated to treatment by
the investigator. The most common adverse event was diarrhea, and diarrhea
was the most common adverse event resulting in discontinuation. Once the
full analysis of the data is completed, Microbia and Forest Laboratories
plan to present the results of these trials at an appropriate scientific
conference.
Based on these data and subject to a complete review of the full
results for both completed studies, the companies intend to initiate Phase
3 trials in both CC and IBS-C patients in the second half of 2008.
CC Trial Design
The U.S. based Phase 2b study was designed to assess the safety,
efficacy, and dose-response of linaclotide in patients with CC. The primary
efficacy endpoint was the change in the overall mean weekly frequency of
SBMs from the pre-treatment baseline through the four-week treatment
period. Following a no-drug washout period of 14-17 days, patients (N=310,
with equal randomization across treatment groups) were randomized to
receive placebo or linaclotide once-daily in the morning at doses of 75
mcg, 150 mcg, 300 mcg or 600 mcg for 28 days. Following completion of the
four weeks of double-blind treatment, patients were followed up for safety
assessments for an additional two weeks. Bowel function measurements
included the number of spontaneous and complete spontaneous bowel movements
(CSBM) compared to baseline, stool consistency using the Bristol Stool Form
Scale (BSFS), and straining. Patient-reported outcomes included measures of
abdominal pain, abdominal discomfort, and bloating on a daily basis, and
constipation severity and overall relief of constipation on a weekly basis.
In addition, the use of rescue medication, end-of-treatment satisfaction,
and disease-specific quality of life were assessed.
IBS-C Trial Design
The U.S. and Canadian based Phase 2b study was designed to assess the
safety, efficacy, and dose-response of linaclotide in patients with IBS-C.
The primary efficacy endpoint was the change in the overall mean weekly
frequency of CSBMs from the pre-treatment baseline through the 12-week
treatment period. Following a no-drug washout period of 14-17 days patients
(N=420, with equal randomization across treatment groups) were randomized
to receive placebo or linaclotide once-daily in the morning at doses of 75
mcg, 150 mcg, 300 mcg or 600 mcg for 12 weeks. Following completion of the
double-blind treatment period, patients were followed up for safety
assessments for an additional two weeks. Bowel function measurements
included the number of SBMs and CSBMs compared to baseline, stool
consistency using the BSFS, and straining. Patient-reported outcomes
included measures of abdominal pain, abdominal discomfort, and bloating on
a daily basis, and constipation severity and overall assessment of IBS
symptoms on a weekly basis. In addition, the use of rescue medication,
end-of-treatment satisfaction, and disease-specific quality of life were
assessed.
Glossary of Terms
Spontaneous bowel movement (SBM): An SBM is a bowel movement that
occurs in the absence of laxative, enema or suppository usage within the
preceding 24 hours.
Complete spontaneous bowel movement (CSBM): A CSBM is an SBM that is
accompanied by the patient self-reporting a feeling of complete evacuation.
Bristol Stool Form Scale (BSFS): A seven-point scale measuring stool
consistency and a surrogate marker of gastrointestinal transit time.
About Chronic Constipation (CC)
As many as 26 million Americans suffer from CC. Patients with CC often
experience hard and lumpy stools, straining during defecation, a sensation
of incomplete evacuation, and fewer than three bowel movements per week.
The discomfort of CC significantly affects patients' quality of life by
impairing their ability to work and participate in typical daily
activities.
About Irritable Bowel Syndrome (IBS)
One out of six adults in developed countries suffers from IBS, a
chronic condition marked by abdominal pain and disturbed bowel function.
IBS accounts for 12% of adult visits to primary care physicians and is the
most common disorder diagnosed by gastroenterologists. Health care costs
associated with IBS exceed $25 billion annually. IBS patients fall into
three subgroups -- constipation-predominant (IBS-C), diarrhea-predominant
(IBS-D), and alternating (IBS-A) -- and 30% to 40% of these patients suffer
from IBS-C. There are currently few available therapies to treat the nine
million U.S. patients diagnosed with IBS-C.
About Linaclotide
Linaclotide is a first-in-class compound currently being tested for the
treatment of IBS-C, CC, and other gastrointestinal disorders. Linaclotide
is an agonist of guanylate cyclase type-C, a receptor found on the lining
of the intestine. In preclinical testing linaclotide was shown to increase
fluid secretion into the intestine, accelerate intestinal transit, and
decrease visceral pain. Linaclotide was designed to exert its effect on the
intestine with minimal systemic exposure. In Phase 2a trials, linaclotide
improved bowel function as measured by both CSBMs and SBMs in patients with
CC and IBS- C. An issued composition of matter patent for linaclotide
provides protection to 2025. In September 2007, Microbia and Forest entered
into a 50/50 collaboration to co-develop and co-promote linaclotide in
United States.
About Microbia
Microbia (http://www.microbia.com) is an entrepreneurial pharmaceutical
company dedicated to the science and art of great drugmaking. The Company
is advancing several clinical candidates-linaclotide for the treatment of
chronic constipation, irritable bowel syndrome with constipation, and other
functional gastrointestinal disorders; and novel, next-generation
cholesterol absorption inhibitors for the treatment of
hypercholesterolemia. Microbia also has a growing pipeline of additional
drug candidates in earlier stages of development. Microbia Precision
Engineering, Inc., a majority-owned subsidiary of Microbia, Inc., is an
industrial biotechnology company developing and commercializing novel
bioprocesses for the production of specialty chemicals. Microbia has raised
$231 million in private equity financing and is located in Cambridge,
Massachusetts.
About Forest Laboratories Inc. and Its Products
Forest Laboratories (http://www.frx.com) is a U.S.-based pharmaceutical
company dedicated to identifying, developing, and delivering products that
make a positive difference in peoples' lives. Forest Laboratories' growing
product line includes Lexapro(R) (escitalopram oxalate), an SSRI indicated
for adults for the initial and maintenance treatment of major depressive
disorder and generalized anxiety disorder; Namenda(R) (memantine HCl), an
N-methyl D-aspartate (NMDA)-receptor antagonist indicated for the treatment
of moderate to severe Alzheimer's disease; Campral(R)* (acamprosate
calcium), indicated in combination with psychosocial support for the
maintenance of abstinence from alcohol in patients with alcohol dependence
who are abstinent at treatment initiation; and Bystolic(TM) (nebivolol), a
beta-adrenergic receptor blocking agent indicated for the treatment of
hypertension. In addition to our growing product line, Forest also
co-promotes the Daiichi Sankyo, Inc. products Benicar(R)* (olmesartan
medoxomil), an angiotensin receptor blocker; Benicar HCT(R)* (olmesartan
medoxomil-hydrochlorothiazide), an angiotensin receptor blocker and
diuretic combination product; and AZOR(TM)* (amlodipine and olmesartan
medoxomil), a calcium channel blocker and angiotensin receptor blocker
combination product, all indicated for the treatment of hypertension.
*Azor is a trademark of Daiichi Sankyo, Inc.; Benicar and Benicar HCT
are registered trademarks of Daiichi Sankyo, Inc.; and Campral is a
registered trademark of Merck Sante s.a.s., subsidiary of Merck KGaA,
Darmstadt, Germany.
Except for the historical information contained herein, this release
contains forward-looking statements within the meaning of the Private
Securities Litigation Reform act of 1995. These statements involve a number
of risks and uncertainties, including the difficulty of predicting FDA
approvals, the acceptance and demand for new pharmaceutical products, the
impact of competitive products and pricing, the timely development and
launch of new products, and the risk factors listed from time to time in
each of Forest Laboratories' Reports on Form 10-K, Quarterly Reports on
Form 10-Q, and any subsequent SEC filings.
Microbia Contact: Forest Contact:
Susan Brady Charles E. Triano
Corporate Communications Vice President, Investor Relations
617|621-8304 212|224-6714
sbrady@microbia.com charles.triano@frx.com
SOURCE Microbia, Inc. and Forest Laboratories, Inc.
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Related links:
http://www.frx.com
http://www.microbia.com
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO
PRN Photo Desk, photodesk@prnewswire.com
CONTACT:
Susan Brady, Corporate Communications of
Microbia, +1-617-621-8304, sbrady@microbia.com; or Charles E.
Triano, Vice President, Investor Relations of Forest
Laboratories, +1-212-224-6714, charles.triano@frx.com
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