Health - Oral Insulin enters late-stage trials

Bangalore: Biocon Ltd’s oral insulin, which aims to be a needleless alternative to the injection, has advanced to late-stage trials, having shown promising results in the mid-stage studies in India.
The company, which will present the phase IIa trial data (phase IIa typically measures dosage requirements) of its new molecule IN 105 at the European Association for the Study of Diabetes meeting in Rome in September, says that for the first time, oral insulin has shown good “dose linearity”. Dose linearity essentially means the response of the drug is proportional to the units consumed, an important parameter in its predictability.
“This study clearly demonstrated a near-perfect linear dose response, which is most encouraging,” says Kiran Mazumdar-Shaw, chairman and managing director of Biocon. Additionally, a significant two-hour post-prandial glucose drop has been seen, which indicates that IN105 has potential in demonstrating efficacy in longer-term trials, she added.
However, what will really determine its clinical efficacy is the next study that will have HbA1c (a measure of blood sugar control over three months) as the end point, says Harish Iyer, head (research and development) at Biocon. The company has conducted four studies so far and is now readying for a large, three-six-month study.
“This will tell us the real positioning of IN105 as an early insulin intervention for patients with early onset of diabetes,” says Mazumdar-Shaw. “Obviously this will mean a new therapeutic paradigm for diabetes that has enormous business prospects for Biocon.” The drug is expected to be launched in 2010.
Initially targeted at type II diabetes, where at least 30% people need some sort of insulin, IN105 is packaged as a tablet using a proprietary polymer technology, acquired by Biocon from US firm Nobex Corp., which allows modification in the drug structure for oral delivery. Biocon later bought all IP assets of Nobex when it filed for bankruptcy in 2005.
“It seems a promising therapy, but I’d look for data from large-scale studies and extended post-marketing surveillance,” says Anoop Misra, director (department of diabetes and metabolic diseases) at Fortis Healthcare Rajan Dhall Hospital, New Delhi. Citing the example of the popular diabetes drug rosiglitazone (brand name: Avandia), he says the drug showed side effects almost seven years after its launch and led US Food and Drug Administration to issue safety warnings.
Even Pfizer Inc.’s inhaled insulin Exubera, whose sales were halted in October, barely a year after its launch, started reporting cases of lung cancer after it hit the market. “Even though we know a lot about insulin, the fact that it is being given through a new route warrants strict surveillance,” cautions Dr Misra.
Biocon, which also makes regular insulin, is aware of the challenges ahead, but is counting on the drug for several reasons. Insulin, says Iyer, has some serious issues, which IN105 manages to get around. It ensures better patient compliance, as it isn’t an injection. Further, insulin is deposited under the skin and leads to weight gain, which is a risk factor for other disorders. “With oral insulin, we think, it’ll be either weight-neutral, or weight loss,” he says.
Finally, because insulin lies in a sort of subcutaneous depot, it acts over a long time and causes hypoglycemia (lower than normal level of glucose) if there’s any slight change in diet, or the insulin intake. IN105, on the other hand, is a rapid acting drug and staves off the risk of hypoglycemia, argues Iyer.
Big Pharma, with its niche in the conventional small molecule drug, hasn’t fancied the biotechnology route for diabetes. The only oral insulin close to the market, according to Dr Misra, is a spray called Oralyn, developed by the Toronto, Canada-based Generex Biotechnology Corp., which has a marketing agreement for India with Shreya Life Sciences Pvt. Ltd, Mumbai.