Topiramate was specifically developed for study in obese individuals with type 2 diabetes to simplify dosing and enhance the compound's profile to create a better treatment option for patients.
Data from the recently completed phase II clinical study with the controlled release formulation of topiramate showed that the controlled release formulation did not provide significant advantages in this population compared to previously conducted studies using the immediate release formulation.
Johnson and Johnson were keen to stress that the move was not based on any new safety information and did not impact the use of topiramate (Topamax). Topamax is an antiepileptic drug, prescribed to control the mild attacks known as partial seizures and convulsions known as grand mal seizures. It is typically added to the treatment regimen when other drugs fail to fully control a patient's attacks.
Topiramate, at pharmacologically relevant concentrations, blocks voltage-dependent sodium channels, augments the activity of the neurotransmitter gamma-aminobutyrate at some subtypes of the GABA-A receptor, antagonizes the AMPA/Kainite subtype of the glutamate receptor, and inhibits the carbonic anhydrase enzyme, particularly isoenzymes II and IV.
The decision by Johnson and Johnson to discontinue the trials on what could've been a drug to treat obesity is a major setback. While there are effective pharmacological treatments on the market, the unpleasant side effects, which include diarrhoea and anal leakage, can discourage many overweight patients.
Available therapies on the market currently include Roche's lipase inhibitor Xenical (orlistat) and Abbott's central nervous system stimulant Reductil (sibutramine). Xenical blocks the absorption of triglycerides by inhibiting pancreatic lipases.
A drug that is undergoing clinical trials is Rimonabant. It is the first drug of its kind designed to block receptors of a substance called cannabinoid 1, suppressing the urge to overeat and other cravings. CB1 receptors are found in the brain and in fat cells, which also play a role in the complex signalling system urging the body to eat more than it needs.
The obesity epidemic has reached epic proportions globally, with more than 1 billion adults overweight - at least 300 million of them clinically obese - and is a major contributor to the global burden of chronic disease and disability, according to the World Health Organization.
In the US, obesity related deaths rose 33 per cent between 1990 and 2000 to an estimated 400,000. And, according to a recent Rand study, by 2020, approximately one in five healthcare dollars spent on people aged 50 to 70 will be due to obesity- related disabilities, if the current trend of overeating and inactivity continues.