Drug Program

Clinical Trial of Paromomycin

Paromomycin is an aminoglycoside antibiotic with anti-parasitic activity. Injectable paromomycin has been tested by OneWorld Health as a treatment for visceral leishmaniasis (VL), also known as kala-azar, occurring on the Indian subcontinent.

OneWorld Health completed a phase III clinical trial of 667 patients in November 2004, the largest trial ever performed for this disease, in collaboration with the Special Programme for Research and Training in Tropical Diseases of the World Health Organization (WHO/TDR). Beginning in June 2003, the phase III trial enrolled patients in Bihar, India, with visceral leishmaniasis that was confirmed by the presence of the parasite in the spleen or bone marrow. Patients were randomized in a ratio of 3 to 1 to receive either paromomycin or the current standard therapy in India, amphotericin B. The safety profile of paromomycin is being compared to that of amphotericin B, and the final clinical cure rates at six months after treatment were determined for both drugs.

The trial was conducted at four centers of excellence in Bihar: the Kala-azar Medical Research Centre and the Kalaazar Research Centre in Muzzafarpur and the Kalaazar Research Centre and the Rajendra Memorial Research Institute in Patna.

OneWorld Health submitted an application for regulatory approval in India for injectable paromomycin in Q2 2006. From the large-scale clinical trials, OneWorld Health believes paromomycin is both safe and effective.

In anticipation of approval, OneWorld Health is conducting a public health surveillance study to understand both the burden of VL and how people access treatment for the disease in affected communities in Bihar. The resulting report will serve as an important foundation for discussions with a variety of government, philanthropic, medical and local non-governmental organizations. The ultimate goal is to structure a comprehensive, sustainable program to distribute the most effective therapies for those most in need in order to control VL in Bihar.

Manufacturing of Paromomycin

Gland Pharma Ltd., in Hyderabad, India, OneWorld Health and IDA expect to supply the needs of the worldwide paromomycin market.

Background of Paromomycin

Paromomycin sulfate is best known for its use as a broad-spectrum aminoglycoside antibiotic. First isolated from culturable filtrates of Streptomyces krestomuceticus by Farmitalia Carlo Erba, it was initially named “aminosidine.” Injectable aminosidine (Gabbromicina) was marketed worldwide in 1959. At the same time, Parke-Davis developed and marketed the drug “paromomycin” (Humatin) as an oral product worldwide. In 1961, paromomycin was shown to be the same as aminosidine.

The spectrum of activity of paromomycin encompasses most Gram-negative and many Gram-positive bacteria, some protozoa and many cestodes. It is poorly absorbed from the gut, so the effects of oral dosing are restricted to the clearing of susceptible bacteria, protozoa and worms from the intestinal lumen. Administered parenterally, it distributes into extravascular fluid space and is effective for treating infections located in most, but not all, parts of the body.

In animals, paromomycin is used both parenterally and orally as an antibiotic. For humans, it is marketed as an oral anti-parasitic drug and a topical anti-leishmaniasis agent. Orally, paromomycin is used to treat giardiasis, amebiasis (Entamoeba hystolytica) and cryptosporidiosis (Cryptosporidium parvum). Topically, paromomycin is currently used to treat Old World cutaneous leishmaniasis (Leishmania major, L. tropica, L. aethopica). Injectable paromomycin has been used experimentally to treat visceral leishmaniasis (primarily due to L. donovani).