Solving a Weighty Problem

Canadians with schizophrenia and bipolar disorders often gain a new lease on life by taking antipsychotic drugs such as Zyprexa (olanzapine). But Zyprexa can cause major weight gain, a side effect that is more than a cosmetic concern. Bulking up can lead to heart disease and the insulin resistance of Type II diabetes, effects which are so pronounced that Zyprexa drug developer Elli Lily has been sued by patient groups in the U.S.

By Karin Kloosterman

The good news is that a new drug therapy developed by Israeli company ObeCure may be able to neutralize Zyprexa's weight-gain side effect. Known as OBE101, the drug is now being tested in a clinical trial in Canada where patients are taking OBE101 in combination with Zyprexa. A leading Canadian expert on schizophrenia who helped plan the coast-to-coast Canadian trial believes that OBE101 may help patients stick to their treatment.

Dr. Lili Kopola, a psychiatrist and researcher at the University of British Columbia's Centre for Complex Disorders, explains: "If patients, young ones especially, are gaining weight, then they don't take their medication. They might have a relapse and that's not a good thing. People in episodes of psychotic illness can also harm themselves and others. We want to save lives and not leave people untreated."

A recent study found that 94 percent of Canadian child psychiatrists prescribe antipsychotics such as Zyprexa to children under the age of nine to treat attention-deficit hyperactivity disorder. What's more, since antipsychotics are also used to treat depression, five out of 100 Canadians might need to take a drug such as Zyprexa at some point in their lifetime.

"Premature death is one factor associated with weight gain," says Dr. Kopola. "What we are hoping to do with this new drug will prevent it."

Dr. Nir Barak, ObeCure's chief scientist, explains: "The reason why OBE101 and Zyprexa are such a good fit is because they both work on the histamine-1 receptor in the brain, the one activates it while the other inhibits it."

OBE101, he says, has already been shown to be effective in causing weight loss among people not suffering from psychotic disorders. In a pilot study of obese women in Israel, Dr. Barak found that subjects receiving the drug lost significantly more weight than their placebo counterparts. A Phase II clinical trial aimed at corroborating these findings is currently underway in the U.S.

Dr. Barak, who is also a nutrition and internal medicine specialist at the Rabin Medical Center in Tel Aviv, notes that in the Israeli study, weight loss could be attributed to a reduction in the intake of fatty foods. "We believe that histamine receptors control a function in our brain that tells us exactly what to eat to achieve a balanced diet. By impacting on this receptor, our drug reduces cravings for fatty foods which leads to a decrease in food consumption."

In another clinical study being carried out in Israel, ObeCure is testing OBE101 in combination with Simvastatin, a widely prescribed cholesterol-lowering drug, to see if the combination can make cholesterol levels drop significantly lower than when Simvastatin is used on its own.

Results of the Canadian Phase II trial for the use of OBE101 in combination with Zyprexa are expected in about a year. If successful, the drug may be able to race through Health Canada regulatory controls. A similar formulation of the drug (betahistine) with different indications has been on the market in Canada and in other countries - but not the U.S. - for decades.

The drug betahistine, which OBE101 was modelled after, was first approved in the mid 1960s for use in the treatment of vertigo. It was taken off the U.S. market by the FDA for lack of clinical evidence in that indication.

Yaffa Beck, CEO of ObeCure, points out that no safety issues were raised. In fact, "a recent post-marketing survey, citing worldwide treatment of more than 100 million patients, shows that the drug has a remarkable safety profile."

Says Beck: "Safety is an especially critical issue with weight-loss drugs because the potential use is so widespread. The recent rejection of the FDA of Rimonabant, a highly touted drug for weight loss that was approved in Europe, is an indication of the high safety profile drugs in this area must achieve."

As OBE101 has a proven safety record, it may only be a matter of time before all Canadians can benefit from the solution to the added weight gain associated with mental health.

For more information, visit www.ObeCure.com.