REHOVOT, Israel, February 28 /PRNewswire/ -- D-Pharm Ltd. announced today publication of preclinical and clinical results obtained with DP-VPA, D-Pharm’s proprietary lipid modified version of valproic acid (VPA). The results, published in Drugs of the Future, 2005, 30, p1212-1218, demonstrate that DP-VPA is well-tolerated in patients with resistant epilepsy and has a marked effect on reducing seizure frequency. DP-VPA treatment provides for serum VPA concentrations far below the accepted therapeutic range for VPA and consequently far fewer adverse effects are observed than with therapeutic levels of VPA.
In the most recent clinical trial, a phase II double-blind, placebo-controlled cross-over study, DP-VPA was tested as add-on therapy for the treatment of complex partial seizures. Analysis of the first period of the study, which lasted 28 days, showed a significant reduction in seizure frequency relative to placebo (mean = 30%, median = 23%, p=0.02) with no significant adverse events. Furthermore, the data suggest that the drug effect was apparent well beyond the treatment period (carry-over effect). This result supports our previous observations of the extended pharmacodynamics of the drug, suggesting a once-a-day treatment regimen and possible anti-epileptic protection even after a missed dose. D-Pharm’s VP for Clinical Development, Dr. Gilad Rosenberg noted, “DP-VPA’s anti-epileptic effect in the presence of sub-therapeutic serum levels of free VPA lends support to our concept that it is the activation of the drug at the epileptic focus that is responsible for the effect observed in this population of difficult-to-treat patients. Considering VPA’s safety profile in past studies, this phase II study suggests that DP-VPA is a safer option to VPA, thus fulfilling our original goal of developing a better tolerated VPA derivative with improved kinetic characteristics.”
DP-VPA is a new chemical entity (NCE) utilising D-Pharm’s proprietary technology, Regulated Activation of Prodrugs (D-RAPTM). DP-VPA comprises VPA linked to a phospholipid moiety to form a prodrug that may be specifically cleaved by phospholipase A2 (PLA2), an enzyme specifically up-regulated in firing neurons. With a seizure imminent, VPA is preferentially released at the site of pathology until PLA2 hyperactivation subsides, enabling precise control over drug action. This pathology regulated drug activation with feedback control provides fine tuning of VPA activation such that efficacy in seizure management may be achieved at very low doses, with a concomitant reduction in dose dependent side-effects.
DP-VPA’s parent drug, valproic acid, has been a major first-line therapy in a wide range of epileptic seizures for more than thirty years and is the drug of choice in treatment of bipolar disorder and prophylaxis of migraine. In 2005, VPA generated total sales of over US$1 billion. However, the use of VPA is associated with the risk of serious dose-related teratogenic, gastrointestinal, neurological and endocrine side effects (e.g. weight gain), limiting its use and interfering with the attainment of effective serum levels. DP-VPA, therefore, represents a promising, new and safer alternative to VPA for the treatment of epilepsy with potential also for migraine prophylaxis and bipolar disorder.
D-Pharm has filed ‘Composition of Matter’ patents for DP-VPA in all major countries worldwide and these have already been granted in the US, Australia and New Zealand.
About D-Pharm
D-Pharm (www.dpharm.com) is a biopharmaceutical company pioneering the development of lipid-based therapeutics. D-Pharm has generated a rich product pipeline from its technology platform: Regulated Activation of Prodrugs (D-RAP(TM)); and its drug discovery platforms Membrane Active Chelators (MAC) and LipidoMimetix, bioactive lipids. D-Pharm is actively seeking development partners for DP-VPA and its other pipeline products, including DP-109, a preclinical candidate for Alzheimer’s disease, which reduces amyloid plaque load and improves cognition and behaviour in transgenic mouse models for Alzheimer’s disease. D-Pharm intends to complete the on-going Phase IIb study of DP-b99 in acute stroke patients before partnering for further development and commercialisation.
Contact: Tami Horovitz D-Pharm Ltd. Tel: +972-8-9385100 Fax: +972-8-9300795 E-mail: thorovitz@dpharm.com
D-Pharm Ltd
CONTACT: Tami Horovitz, D-Pharm Ltd., Tel: +972-8-9385100, Fax:+972-8-9300795, E-mail: thorovitz@dpharm.com
