Napo Announces Positive Clinical Data Indicating Crofelemer, Could Effectively Treat Cholera
September 22 2008 - 12:15PM
PR Newswire (US)
SAN FRANCISCO, Sept. 22 /PRNewswire/ -- Napo Pharmaceuticals (LSE:
NAPL/NAPU) today announces positive clinical data on the
effectiveness of crofelemer from a study for CRO-ID in treating
severely ill cholera patients in conjunction with an antibiotic and
rehydration therapy. A double-blind placebo-controlled study was
conducted in one hundred (100) patients with confirmed severe
cholera. Patients were randomized to placebo or 125 mg crofelemer
every 6 hours or 250 mg crofelemer every 6 hours in a 1:2:2
randomization scheme. This single center trial was conducted at the
International Centre for Diarrhoeal Disease Research (ICDDR, B) in
Dhaka, Bangladesh, popularly known as the "cholera hospital" for
the state-of-the-art treatment of cholera patients. The purpose of
the trial was to obtain a therapeutic proof-of-concept in the
treatment of cholera, by a reduction in the life-threatening fluid
loss characteristic of cholera infection. In addition to receiving
crofelemer, all patients received a single oral dose of
azithromycin and rehydration therapy. These severely ill cholera
patients, even when receiving the antibiotic azithromycin and
rehydration therapy (but not crofelemer), averaged approximately
8.5 liters of stool volume output during the first 24 hour period.
The primary endpoint in this study was the reduction in stool
volume output normalized to the body weight of the cholera
patients. Following the exclusion of three outlier patients, the
data demonstrates that a crofelemer dose of 125 mg every 6 hours
reduced the amount of stool volume output normalized to body weight
by 32% (p=0.028, Mann-Whitney test) in the first 6 hour period (0-6
hours). A 31% reduction in normalized stool volume output was also
observed during the first 12 hour period (0-12 hours) with
crofelemer 125 mg every 6 hours (p=0.072, Mann-Whitney test). The
higher dose of crofelemer (250 mg every 6 hours) also showed a
trend towards significance in the first 12 hour period (0-12 hours,
p=0.155, Mann-Whitney test). Crofelemer was well tolerated in
cholera patients. Crofelemer was safely and effectively used in
combination with the antibiotic, azithromycin, and rehydration
therapy. Both Napo and ICDDR, B, upon receipt of additional
funding, would like to continue with studies ranging to lower
dosing regimens with crofelemer, and also include the treatment of
children with development of a pediatric formulation of the
product. Elements of the cholera study in Bangladesh were funded by
the National Institutes of Allergy and Infectious Disease. Napo is
currently conducting a Phase 3 trial for crofelemer for chronic
diarrhea in people living with HIV/AIDS ("CRO-HIV"). This
indication has been fast-tracked by the FDA. Napo expects to file
its first NDA around mid-2009 for this indication, subject to the
receipt of further funding. Dr. Pradip Bardhan, Scientist and Head
of Special Care Unit at ICDDR, B and the principal investigator,
commented that "Crofelemer produces an impressive reduction in
stool volume output within the first 12 hour period. There is a
clear need for new agents to produce reduction in stool volume
output in the first 12-18 hours, which is the period where the
patients are at maximum risk for dehydration. Both doses of
crofelemer were well tolerated and no drug related adverse events
were observed in the cholera patients in this study. As a novel
antisecretory agent, crofelemer represents a complementary
mechanism to existing standard-of-care treatment of cholera, which
consists of administering rehydration therapy and antibiotics, with
the inherent risk of resistance generation." Lisa Conte, Napo's
CEO, commented, "Napo is so pleased to be reporting this powerful
clinical data relating to the treatment of one of the most extreme
cause of secretory/watery diarrhea with crofelemer. These results
extend the recent clinical data relating to the treatment with
crofelemer of acute infectious diarrhea of multiple etiologies in
adult patients in India (see announcement dated April 10, 2008).
The mechanistic cause of these diarrheas is similar to that which
effects chronic diarrhea in people living with HIV/AIDS, an
indication for which Napo is in final Phase 3 development with
crofelemer in the US ('CRO-HIV'). Our business strategy focus on
diseases of both lucrative western markets and imperative global
health needs." About cholera Vibrio cholerae is an intestinal
infection which results in the abrupt loss of large volumes of
electrolyte rich watery stools and vomiting, leading to severe and
rapidly progressing dehydration and shock. Without adequate
rehydration therapy, the water loss associated with severe cholera
results in death for about half of affected individuals. The
cholera toxin causes the intestine to secrete watery fluid in
volumes far exceeding the intestinal absorptive capacity. Current
standard-of-care therapy focuses on rehydration therapy, either
intravenous or oral, and antibiotic therapy to target the
infectious agent. There are no current therapies for cholera which
decrease the secretion of fluid into the small intestine. The
benefits of shorter and less severe duration of diarrhea include
reduced hospitalization time; reduced volume of necessary
rehydration therapy; and reduced V. cholerae infected faecal
excretion, thereby reducing the risk of transmission of infection
to other family members and nosocomial infections at clinic
settings. Antibiotic resistance is a growing problem in cholera
infection, with one 2005 study in Bangladesh demonstrating
multi-drug resistance in 79% of the isolates from patients
attending the ICDDR, B in Dhaka. Cholera, identified and detailed
from the beginning of recorded history, was initially endemic to
the Indian sub-continent. The disease began spreading almost 200
years ago, and is now pandemic and persists primarily in the
developing world. The bacteria spreads through contaminated water
and food. Because outbreaks can become massive epidemics, it is a
reportable disease, and is listed as a category B bioterrorism
agent/disease by the Department of Health and Human Services -
Centers for Disease Control. About Napo Pharmaceuticals, Inc. Napo
Pharmaceuticals, Inc. focuses on the development and
commercialization of proprietary pharmaceuticals for the global
marketplace in collaboration with local partners. Napo was founded
in November 2001, and is based in California, USA with a subsidiary
in Mumbai, India. Napo's late-stage proprietary gastro-intestinal
compound, crofelemer, is in various stages of clinical development
for four distinct product indications, including a late-stage Phase
3 program: -- CRO-HIV for chronic diarrhea in people living with
HIV/AIDS, Phase 3 -- CRO-IBS for irritable bowel syndrome
("D-IBS"), Phase 2 -- CRO-ID for acute infectious diarrhea
(including cholera), Phase 2 -- CRO-PED for pediatric diarrhea,
Phase 1 The FDA has granted fast-track status to CRO-IBS and
CRO-HIV. Crofelemer, a proprietary patented agent, is extracted
from Croton lechleri, a medicinal plant which can be sustainably
harvested from several countries in South America. Napo also plans
to develop an early clinical stage product, NP-500, for the
treatment of insulin resistant diseases of Type II diabetes and
metabolic syndrome (Syndrome X; pre-diabetic syndrome).
Additionally, Napo has a plant library of approximately 2,300
medicinal plants from tropical regions, and Napo has entered two
screening relationship associated with this collection. Currently,
products are based on the chemical and biological diversity derived
from plants with medicinal properties, but future products may be
in-licensed from other sources. Napo has partnerships with Glenmark
Pharmaceuticals Limited of India and AsiaPharm Group Ltd. of China.
The Company has also established an alliance with Direct Relief
International to provide access to and distribution of crofelemer
for pediatric populations in disaster and resource-constrained
geographies, if the product achieves approval and registration by
the FDA. For more information please visit
http://www.napopharma.com/. About Crofelemer Crofelemer, a
proprietary patented agent, is extracted from Croton lechleri, a
medicinal plant which can be sustainably harvested from several
countries in South America. Crofelemer is in various stages of
clinical development for four distinct product indications, one in
Phase 3, two in Phase 2 and one in Phase 1. Crofelemer has been
tested in trials involving approximately 1900 patients in
double-blind placebo-controlled, mostly published trials of AIDS
diarrhea, diarrhea-predominant IBS, and acute infectious diarrhea.
It is generally well tolerated and has shown significant
anti-diarrheal activities and improvement in gastrointestinal
symptoms. Crofelemer produces several effects when administered
orally providing for activity in several disease indications.
Crofelemer's first in class anti-secretory mechanism reduces excess
fluid secreted into the gastro-intestinal tract, while its
anti-inflammatory and analgesic activity may provide the rationale
for its significant benefit in abdominal pain. Crofelemer acts
locally in the intestines, with limited systemic exposure. This
announcement contains forward-looking statements relating to Napo
Pharmaceuticals and its products that involve risks and
uncertainties, including statements regarding future products and
developments that are not historical facts. Such statements are
only predictions and the company's actual results may differ
materially from those anticipated in these forward-looking
statements. These statements can be identified by the use of
forward-looking terminology such as "believe," "expect," "may,"
"will," "should,' "could," "project," "plan," "seek," "intend," or
"anticipate" or the negative thereof or comparable terminology and
statements about industry trends and Napo's future performance,
operations and products. DATASOURCE: Napo Pharmaceuticals, Inc.
CONTACT: Maureen Dempsey, +1-212-300-1806, , for Napo
Pharmaceuticals, Inc. Web Site: http://www.napopharma.com/
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