Tioga Pharmaceuticals, Inc.
announced the results of a recent Phase 2b study of its oral kappa opioid
receptor agonist, asimadoline, which demonstrated statistically significant
results in the treatment of Irritable Bowel Syndrome (IBS). Asimadoline
produced significant improvement in diarrhea-predominant (D-IBS) and
alternating (A-IBS) patients across multiple parameters including the
primary endpoint of pain, as well as secondary endpoints of urgency,
frequency and bloating in both males and females. In D-IBS patients,
therapeutic benefit was observed within the first month of treatment and
was sustained for the three month duration of the trial. Asimadoline
appeared to be well tolerated with no adverse events occurring in a
dose-dependent manner throughout the randomized, double-blind,
placebo-controlled, dose-ranging clinical trial involving 596 subjects.
These data were featured today in a late-breaking oral presentation session
at the Digestive Disease Week 2008 Annual Meeting.
Study Results
Of the 596 patients randomized in the trial, approximately 33 percent
were characterized as D-IBS, 37 percent constipation predominant (C-IBS)
and 31 percent alternating between diarrhea and constipation (A-IBS).
-- In the overall patient group, patients with at least moderate pain
achieved a 17 percent improvement in percent number of months with
adequate relief of IBS pain compared to placebo (40 percent vs. 23
percent) with both the 0.5 mg (p=0.006) and the 1.0 mg (p=0.005) dose
of asimadoline.
- Evaluation by IBS subtype revealed benefit in D-IBS and A-IBS
patients.
- Benefit in C-IBS patients was not observed.
- The rate of adverse events was similar in asimadoline and placebo
treated subjects.
-- Patients with D-IBS with at least moderate pain achieved a 27 percent
improvement in the percent number of months with adequate relief of
IBS pain compared to placebo (47 percent vs. 20 percent, p=0.011) with
the 0.5mg dose of asimadoline.
- A 25 percent increase in pain free days was seen with 0.5 mg
asimadoline as compared with placebo (p=0.001) during the 12-week
dosing period. This represents an increase of approximately 20
pain free days over that seen with placebo.
- Statistically significant (p
- Benefit was seen in female and male patients.
-- Patients with A-IBS with at least moderate pain achieved a 23 percent
improvement in the percent number of months with adequate relief of
IBS pain compared to placebo (50 percent vs. 27 percent, p=0.022) with
a 1.0 mg dose of asimadoline.
- Statistically significant benefit was also seen in the secondary
endpoint of adequate relief of IBS symptoms in patients receiving
the 1.0 mg dose of asimadoline compared to placebo (57 percent vs.
33 percent, p=0.032).
- Benefit was seen in female and male patients.
Study Design
D-IBS, C-IBS, and A-IBS patients were recruited. Patients underwent a
two-week screening, a 12-week treatment and a four-week follow-up period,
and they received identical appearing placebo, 0.15 mg, 0.5 mg or 1.0 mg
tablets of asimadoline twice daily for the treatment period. Throughout the
trial, patients entered data daily by IVRS (interactive voice response
system). The primary endpoint was number of months a patient was a
responder for adequate relief of pain, where the primary measure was the
question, "In the past 7 days have you had adequate relief of your IBS pain
or discomfort?" asked once every 7 days. A monthly responder replied "yes"
at least three weeks per month. The secondary endpoints were abdominal
pain, stool frequency and consistency, urgency, bloating, adequate relief
of IBS symptoms and straining. Secondary endpoints were also collected
using IVRS. Adverse events, labs and echocardiograms were also collected.
About Irritable Bowel Syndrome
Irritable bowel syndrome is a common, chronic gastrointestinal disorder
characterized by abdominal pain and discomfort associated with alterations
in bowel habits. The bowel abnormalities may manifest as
diarrhea-predominant disease, constipation-predominant disease, or
alternation between diarrhea and constipation. IBS is estimated to afflict
approximately 12 percent of the adult population in the United States and
Europe, with roughly equal prevalence of each subtype. For reasons that
remain unknown, IBS is a female-predominant disorder, with two-thirds to
three-quarters of the subjects being female.
Lotronex (alosetron), a selective 5-HT3 receptor antagonist, is the
only drug currently approved by the FDA for the treatment of D-IBS;
however, due to safety concerns, Lotronex was removed from the market in
2001 and re-launched in 2002 under a strict risk management program. No
treatment is currently approved by the FDA for A-IBS. There is, therefore,
an urgent unmet clinical need for a safe and effective treatment for the 20
million Americans who suffer from D-IBS and A-IBS.
About Asimadoline
Asimadoline is an orally administered small molecule that is a highly
selective kappa opioid receptor agonist. Kappa opioid receptors are found
in the digestive tract and are believed to play an important role in
control of visceral pain and bowel motility. Asimadoline was originally
discovered by Merck KGaA of Darmstadt, Germany. In 2005, Tioga purchased
asimadoline from Merck and acquired by assignment all worldwide rights.
Asimadoline has been tested in over 1100 subjects and has demonstrated a
promising safety profile.
About Tioga
Tioga Pharmaceuticals, Inc. is a pharmaceutical company headquartered
in San Diego, CA focused on developing novel treatments for
gastrointestinal diseases. Tioga is currently planning Phase 3 development
of asimadoline for the treatment of D-IBS and A-IBS and a Phase 2b trial of
asimadoline for the treatment of functional dyspepsia. Both disorders
represent a large unmet medical need and a substantial market opportunity.
For more information, please visit tiogapharma.
Tioga Pharmaceuticals, Inc.
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