Acacia Pharma to Progress Two Projects for Nausea and Vomiting, and Xerostomia into Clinical Development
Acacia Pharma, a pharmaceutical company specializing in the development of drugs for cancer supportive care, announces the initiation of two clinical development programmes: APD421 for the prevention and treatment of nausea and vomiting; and
APD515 for the treatment of xerostomia (dry mouth). Clinical studies will commence in the final quarter of 2010.
APD421 is an intravenous formulation of a currently marketed drug for the new use of prevention and treatment of nausea and vomiting. The drug is a dopamine D
2
antagonist and data generated by Acacia Pharma suggest that it could offer advantages over existing
D
2
antagonists given its significantly improved therapeutic window. APD421 has been shown by Acacia Pharma to be highly effective in preclinical models of both postoperative nausea and vomiting (PONV) and chemotherapy-induced nausea and vomiting (CINV). Initially, APD421 will be developed for PONV, as this provides the most rapid development and commercialization opportunity owing to the acute nature of the condition and the large number of surgical procedures performed. It will then be developed for CINV once clinical proof-of-concept has been shown. The active ingredient in APD421 also has the potential to be formulated in noninjectable presentations for use by patients outside the hospital environment. This is an important benefit for patients being treated for CINV on an outpatient basis. PONV occurs in approximately 35% of all surgical patients (there are >130 million surgical procedures worldwide per annum) and 70% of high-risk patients and is a major concern in patients undergoing general anaesthesia. PONV is currently treated using a multimodal approach, including the use of combination pharmacotherapy. Despite this about a third of patients given prophylaxis require rescue therapy in the first 6 h after surgery and 40% in the first
24 h. CINV is reasonably well controlled in the early phase (that is, when patients are dosed with chemotherapy), but less well in the late phase when patients go home.
APD515 is an optimized oromucosal formulation of a currently marketed drug for the new use of treatment of xerostomia. Xerostomia, or dry mouth, can result from reduced salivary flow or altered salivary composition and occurs as a result of salivary gland dysfunction. APD515 has been developed by Acacia Pharma as a liquid formulation to be applied directly to the inner lining of the mouth allowing it to act locally on the salivary glands, with little or no absorption into the general circulation. Avoiding systemic exposure greatly reduces the potential for side effects, a significant advantage over currently approved salivary stimulants, which have to be dosed orally. Preclinical efficacy and safety investigations of APD515 have been completed supporting the decision to move the product into clinical development. Initially, APD515 will be developed as a treatment for xerostomia in advanced cancer patients. It has been reported that 70–80% of advanced cancer patients suffer from xerostomia either as a direct result of their disease, their chemotherapy or as a consequence of concomitant medicines.
Xerostomia is also common among the elderly and in patients taking a wide variety of common medicines, including tranquilisers, antidepressants, opioid painkillers and
H
2
-blockers. APD515 will be developed in other such populations when clinical proof-of-concept has been obtained.

Acacia Pharma’s CEO, Dr Julian Gilbert, commented: “We are delighted to announce our decision to move both APD421 and APD515 into clinical development in such significant areas of unmet need as nausea and vomiting, and xerostomia. Acacia
Pharma’s objective is to provide physicians with supportive care products that allow patients to receive the optimal treatment for their primary condition and significantly improve their quality of life.
“Both products comprise new uses for drugs currently marketed in a completely different indication, and both work by a clinically validated mechanism of action. This approach to generating new products is able greatly to reduce development risk and time to market.”