Licensing arrangement reached for antiepileptic drug developed at Hebrew University

The licensing is primarly for valrocemide. The efficacy of valrocemide as an antiepileptic drug has been demonstrated in a small clinical study. Shire intends to study the drug as a candidate for application in a number of central nervous system conditions.

Valrocemide was discovered by a team led by Meir Bialer, the David H. Eisenberg Professor of Pharmacy at the Hebrew University School of Pharmacy. Bialer, a leader in the discovery of antiepileptic agents, has authored over 180 publications in the area of pharmacokinetics, antiepileptics and central nervous system (CNS) drugs.

Epilepsy is a widespread neurological disease. Approximately one percent of the world’s population suffers from it, and annual sales of antiepileptic drugs in the U.S. amount to more than $3 billion per year.

There are several existing drugs on the market for patients with epilepsy. However, about one-third of the patients do not react positively to these treatments, and as a result they continue to suffer periodic epileptic seizures. There is a need, therefore, to develop new anti-epileptic drugs that will provide relief to patients who are not seizure-free or who suffer serious side effects from existing drugs.

The brain contains amino acids that serve as neurotransmitters, either excitatory or inhibitory neural transmissions within the central nervous system. Epilepsy is caused, among other reasons, by disturbances in the balance between these two functions: a rise in the level of the excitatory amino acids or a reduction in the level of the inhibitory acids.

Glycine is one of the inhibitory amino acids, and increasing its concentration in the brain has an antiepileptic effect. However, it is impossible to administer it to patients in its natural state, because it does not penetrate the blood-brain barrier that prevents medications from reaching their CNS target sites.

Prof. Bialer’s research team, which included his former doctoral student, Dr. Salim Hadad, worked to develop a glycine derivative which would penetrate the blood-brain barrier and would subsequently be cleared out of the body by a predesigned elimination pathway in order to avoid undesirable side effects which may be caused by toxic metabolic substances (metabolites).

The new CNS drug, valrocemide, is a combination of a known antiepileptic drug, valproic acid, and a glycine derivative, glycinamide. Valrocemide has been shown to be one of the most effective drugs among a large, analogous series of molecules which have been developed in Prof. Bialer’s laboratory.