Napo Pharmaceuticals
Crofelemer
A proprietary gastro-intestinal compound in clinical development for four distinct product indications
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Ethics Committee Approval Granted for Multiple- Dose Continuation of Phase 2 Clinical Trial of Crofelemer for Treatment of Secretory Diarrhea Associated with Cholera Infection
Addendum to Company safety disclosure of Feb. 15, 2007
South San Francisco, California, 21 May, 2007- Napo Pharmaceuticals, Inc., (LSE: NAPL), which focuses on the development and commercialisation of proprietary pharmaceuticals for the global marketplace in collaboration with local partners, announces today that it has received approval from the Ethics Committee at International Centre for Diarrheal Disease Research (ICDDR,B) in Bangladesh, to continue the Phase 2 trial of crofelemer (CRO-ID) for the treatment of secretory Diarrhea associated with cholera, at lowers doses and different formulation(s).
As previously announced, Napo initiated the study in Bangladesh at the International Centre for Diarrheal Disease Research (ICDDR,B) in the first quarter of 2006. The ICDDR,B Centre treats approximately 100,000 patients suffering from Diarrhea each year in its Dhaka hospital. The dose of crofelemer used in the first 61 patients was amongst the highest previously tested in patients, and it was administered in an experimental formulation. The initial study design was for one treatment arm compared to placebo.
As set out in an announcement dates 15 February 2007, an interim analysis confirmed the safety profile of crofelemer in this patient population. Based on the results of this safety analysis and other clinical, pre-clinical and formulation data generated since the original dose selection, Napo requested approval from the Ethics Committee at the ICDDR,B to utilize a lower total daily dose and different formulations.
Crofelemer, which has now been tested in 1500 patients across four different gastro-intestinal indications, continues to be well-tolerated with no drug-related serious adverse events noted. alEven at very high doses, crofelemer is well tolerated, though there are some suggestions of diminished therapeutic response at higher dosing levels. Napo continues to evaluate the dose-response to determine the optimal dose of crofelemer in a variety of disease states, including cholera and chronic diarrhea in people with HIV/AIDS.
Lisa Conte, Napo's CEO, stated: "We look forward to a continuation of the cholera trial and expect to release safety and efficacy results from the trial prior to the end of 2007. I'd also like to note that Napo filed a patent on its manufacturing process for crofelemer in March 2007. This patent covers Napo's current manufacturing process as well as numerous aspects of lower cost manufacturing process that is being developed. Development of a lower cost manufacturing process is important so that crofelemer, once approved, can be used for indications such as cholera and acute infectious Diarrhea in resource constrained areas of the world. "
About Cholera
Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae. The infection can be severe and life-threatening, characterized by profuse watery diarrhea, vomiting, and leg cramps. In such individuals, rapid loss of body fluids leads to dehydration and shock. Without treatment, death can occur within hours.. The primary current treatment is replacement of fluid which is complicated by the continued production of high volume watery Diarrhea. The disease continues to occur endemically and epidemically in South-East Asia, South Asia, Africa and South America but also sporadically occurs in the South Eastern United States. In 2005, WHO reported the incidence of cholera resistance was 100 percent for certain antibiotics in certain outbreaks. Diarrhea is the result of stimulation of active chloride secretion across the CFTR (cystic fibrosis transport regulator) channel by cholera toxin.
For more information please contact:
Napo Pharmaceuticals, Inc.
Lisa Conte, Chief Executive Officer
(001) + 650 616 1902
Charles Thompson, Chief Financial Officer
(001) + 650 616 1903
Buchanan Communications
020 7466 5000
Tim Anderson, Mary-Jane Johnson
Nomura Code Securities Limited
020 7776 1205
Clare Terlouw
About Napo Pharmaceuticals, Inc.
Napo Pharmaceuticals Inc., focuses on the development and commercialisation 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 AIDS Diarrhea, Phase 3
- CRO-IBS for Diarrhea irritable bowel syndrome ("D-IBS"), Phase 2
- CRO-ID for acute infectious Diarrhea (including cholera), Phase 2
- CRO-PED for paediatric 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. Experimental studies have shown that crofelemer inhibits chloride secretion across the CFTR transporter in various animal models of diarrhea, including cholera toxin treatment. Napo also plans to develop a clinical stage product, NP-500, for the treatment of insulin resistant diseases of Type II diabetes and metabolic syndrome (Syndrome X; pre-diabetic syndrome). Napo also has a plant library of approximately 2,300 medicinal plants from tropical regions and Napo has entered into screening relationships 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 Trine Pharmaceuticals, Inc. of the United States of America; Glenmark Pharmaceuticals Limited of India; and AsiaPharm Group Ltd. of China. For more information please visit 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. These products have been tested in trials involving approximately 1500 patients in double-blind placebo-controlled, mostly published trials of AIDS Diarrhea, Diarrhea-predominant IBS, and acute infectious Diarrhea. The products are generally well tolerated and have 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 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.