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Napo Announces Positive Clinical Data Indicating Crofelemer, Could Effectively Treat Cholera

Update: Fulyzaq (crofelemer) Now FDA Approved - December 31, 2012

SAN FRANCISCO, September 22, 2008 /PRNewswire/ -- Napo Pharmaceuticals 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.

 

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."

 

, 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."

 

 

 

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 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.

 

 

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:

 

 

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 www.napopharma.com.

 

 

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.

 

 

CONTACT: Maureen Dempsey, +1-212-300-1806, , forNapo Pharmaceuticals, Inc. mdempsey@apcoworldwide.com

Web site: http://www.napopharma.com/

Ticker Symbol: (LSE:NAPL),(LSE:NAPU)

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Posted: September 2008

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