Pro-Pharmaceuticals to submit NDA for functional excipient in cancer treatment

Pro-Pharmaceuticals Inc, a US-based developer of novel carbohydrate compounds, is a step closer in its plans to submit a New Drug Application (NDA) for a functional excipient, to be co-administered with 5- Fluorouracil (5-FU) to treat cancer patients.

Excipients functional roles in drug manufacture can include modulating solubility, increasing stability and bioavailability. In complex products such as chemotherapeutics, the functional role of an excipient is also important when used as a drug delivery system to reduce toxicity or increase efficacy.

The Company is seeking approval for co-administration of Davanat with FDA-approved 5-FU for intravenous injection for the treatment of cancer. 5-FU is one of the most widely used chemotherapy drugs in the world and is used to treat various types of cancers, including colorectal, breast and gastrointestinal.

Davanat is a polysaccharide, carbohydrate polymer, composed of mannose and galactose (galactomannan). It is believed the excipient's mode of action is based upon binding to lectins on the surface of cancer cells. Lectins are carbohydrate-binding proteins found on cell surfaces. It is thought that Davanat, targets specific lectin receptors (Galectins) that are over-expressed on cancer cells. Current research indicates that Galectins affect cell development and play important roles in cancer, including tumour cell survival, angiogenesis and tumour metastasis. This form of targeted delivery may allow for higher doses of chemotherapy administration with no increase in toxicity.

Galactomannan are approved for formulation and deliveries, such as oral, topical and vaginal delivery of drugs. Davanat, extends the use of galactomannan to the delivery of chemotherapeutic drugs.

The company is also continuing its clinical development plan for Davanat in combination with 5-FU and other chemotherapy and biological drugs, such as leucovorin and Avastin. It plans to initiate a Phase lll trial after reporting interim results from the ongoing Phase ll trials.

"In March, we sent the FDA substantial information on chemistry and completed pre-clinical and clinical data, along with a list of questions to submit an NDA to allow Davanat, to be used as a functional excipient, intravenously with 5-FU, for cancer applications for a filing under Section 505 (b)(2)," said David Platt, president & ceo, Pro-Pharmaceuticals.

"The FDA's response provides us with a clear roadmap in terms of what additional information, primarily manufacturing, they need to allow our NDA submission. No additional toxicology or clinical tests or trials are required. We plan to file an NDA submission as soon as we complete the additional manufacturing information needed."

The Company's technology capitalizes on the natural property of carbohydrates to increase the efficacy and reduce the toxicity of chemotherapeutics; "rescue" drugs that were shelved for toxicity or "half-life" issues; increase the solubility of existing drugs, and develop carbohydrate polymers as new chemical entities. It has been conducting clinical and pre-clinical studies with its lead compound, Davanat, in combination with 5-FU, leucovorin, irinotecan, doxorubicin, oxaliplatin, paclitaxel, cisplatin, and bevacizumab (Avastin).

Results show that Davanat, exhibits a broad spectrum of activity with tested drugs. The company is developing additional carbohydrate-based therapeutic compounds that are currently in the pre-clinical stage of development.