Glenmark readies for launch of Napo's crofelemer
This article was originally published in Scrip
Glenmark Pharmaceuticals is preparing for the launch of Napo Pharmaceuticals' novel anti-secretory gastrointestinal agent, crofelemer, in 140 emerging and developing world countries, following positive Phase III results for the product for the treatment of chronic diarrhoea in people living with HIV/AIDS.
Crofelemer is an oligomeric proanthocyanidin compound derived from the latex of Croton lecheri, a medicinal tree found in South America. It acts locally in the gastrointestinal tract to regulate fluid balance but without being significantly systemically absorbed itself.
Napo anticipates a pre-NDA meeting with the US FDA in the first quarter of next year and expects to launch crofelemer in 2012 in the US and globally. Glenmark has the exclusive licence to commercialise crofelemer in 140 rest of world (RoW) territories including India for indications related to HIV and acute adult and paediatric diarrhoea.
Glenmark noted that the prevalence of HIV is very high in its territories, with India alone estimated to have 2.5 million cases and South Africa having about nine million people living with HIV. The company had earlier said that it expects potential peak sales of $80 million in RoW markets alone for the HIV-related diarrhoea indication, in addition to sales in adult acute infectious diarrhoea.
"Glenmark is in the process of conducting and planning further development activities relating to clinical development, manufacturing as well as regulatory submissions. Resources are being allocated for each of these activities for the RoW markets where Glenmark holds rights," the company told Scrip. In India, Glenmark is conducting Phase II trials for acute infectious diarrhoea with crofelemer.
Glenmark also sees good potential for the drug in paediatric diarrhoea. Glenmark's CEO and managing director, Glenn Saldanha, said that most of the markets where Glenmark has exclusive rights have a significant incidence of acute diarrhoea, especially in young children. Napo has financed certain paediatric development efforts through a royalty-based funding vehicle called the Crofelemer Access Program.
Crofelemer has been licensed to Salix Pharmaceuticals for the treatment of chronic diarrhoea in people living with HIV, or HIV–associated diarrhoea, and the additional indications of paediatric diarrhoea and acute infectious diarrhoea in North America, Europe (excluding Iceland, Liechtenstein, Norway and Switzerland) and Japan.
Salix also has a worldwide licence to all other possible human indications, including irritable bowel syndrome. Salix estimates that the HIV-associated diarrhoea market opportunity alone in the US may be $300 million annually.
Glenmark and Salix have entered into a supply agreement for crofelemer’s active pharmaceutical ingredient (API), with Glenmark expected to invest in a stand-alone API facility for the product. Crofelemer is also licensed to AsiaPharm in greater China for diarrhoea indications.
ADVENT study
Napo recently completed the top-line analysis of the primary efficacy endpoint from the Phase III ADVENT placebo-controlled study to evaluate the safety and efficacy of crofelemer in the treatment of chronic diarrhoea in people living with HIV/AIDS on antiretroviral therapy.
The first stage of the two-stage adaptive study evaluated the effects of 125mg, 250mg and 500mg crofelemer twice daily against a placebo-controlled group following 28 days of treatment as a balanced randomisation. After the completion of four weeks of dosing in about 200 patients, with about 50 patients in each group, a crofelemer dose of 125mg twice daily was selected by an independent committee for the second stage of the trial.
Crofelemer at a dose of 125mg twice daily demonstrated a "highly statistically significant" improvement in the primary responder analysis, defined as patients having two or less watery stools in two of the four weeks of the placebo-controlled phase, Napo said.
The ADVENT trial is being conducted under US fast-track status and has been part of a special protocol assessment (SPA) agreement with the US FDA. Given the adaptive nature of the trial design, the pre-specified p-value for the treatment difference was 0.025, while the p-value achieved in the ADVENT trial was 0.0096. The results met the efficacy targets set out in the SPA agreement.
Crofelemer also has US fast-track status for irritable bowel syndrome-related indications.