REHOVOT, Israel - Epilepsy patients who cannot be treated with valproic acid because of side effects might have a new treatment option on the way.
D-Pharm reported last week the successful completion of two consecutive Phase I studies in human volunteers with the company's proprietary oral drug, DP-VPA, a new drug for epilepsy, manic depression and migraines. DP-VPA is safer in humans than its parent-derivative, valproic acid (VPA), the well-established anti-convulsive drug, currently used for the treatment of epilepsy, bipolar disorder and migraine prophylaxis. Phase II studies, involving child and adult epilepsy, are being planned.
The Phase I double-blind, randomized, placebo-controlled studies, carried out in France, found no biological changes or side effects at any dose. Single oral doses of DP-VPA or placebo were taken by 29 healthy male volunteers in five dosage groups, and repeated daily administration for seven days were given to 27 healthy male volunteers in three dosage groups. All treatments were well tolerated. At the highest doses, some mild or moderate gastrointestinal side effects were observed, but none of the volunteers dropped out of the trials.
"We are encouraged by these clinical results, since DP-VPA even in very high doses does not seem to cause the adverse neurological and liver-function side effects usually associated with the use of valproic acid," Itzchak Angel, vice president of research and development at D-Pharm, told BioWorld International.
Earlier preclinical studies in a variety of animal models of epilepsy demonstrated that D-Pharm's drug is up to 80 times more effective with no side effects. "Perhaps more significantly, the studies demonstrated definitively that D-Pharm's proprietary drug delivery technology platform known as Regulated Activation of Prodrugs produces a greatly enhanced efficacy/safety profile," said Alex Kozak, D-Pharm's president and CEO.
The DP-VPA is comprised of a phospholipid carrier chemically linked to a moiety of valproic acid. Cleavage of DP-VPA with liberation of active valproic acid occurs locally and selectively inside diseased cells, responding to an enzyme characteristically elevated during an epileptic seizure and only for as long as the pathological condition exists.
Valproic acid, the major first-line therapy for epileptic seizures for over 30 years, generates annual sales of more than $880 million for epilepsy, bipolar disorder and prophylaxis of migraine. However, prolonged use of VPA is associated with the risk of serious side effects such as hepatotoxicity and teratogenicity, limiting use especially in children and in women of childbearing age. In addition, VPA's sedative effect and toxicity interfere with the attainment of effective doses and has deleterious effects on patients' quality of life.
D-Pharm is one of Israel's standout start-up biopharmas, backed by $23 million in venture capital. Another novel compound in D-Pharm's pipeline is DP-b99, a neuroprotective drug based on modulation of cellular divalent ion homeostasis. DP-b99 is scheduled to enter Phase I clinical studies by the end of this year. Other drug programs for inflammation, neurodegeneration, AIDS and cancer are at various stages of development. D-RAPTM platform is one of D-Pharm's Selective Molecular Activation and Routing technologies able to respond to the body's stress response mechanisms and molecular trafficking systems to selectively target and activate drugs.