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Avandia News
Safety Review On Diabetes Drug Avandia
by Niall Hunter, Editor
20/08/2007 - A review of the possible heart side-effects of the diabetes drug Avandia is due to be completed in October, according to the Irish Medicines Board (IMB).
The European Medicines Agency (EMEA), of which the IMB is a member, is currently performing a re-evaluation of the benefits and risks of taking the drug in view of concerns on its cardiovascular safety, and this re-evaluation is due to be concluded in October, according to the IMB.
The US Food and Drug Administration (FDA) last week announced that a 'black box' warning would be put on the Avandia label advising users of an increased risk of heart failure.
Back in May an article published in the New England Journal of Medicine raised concerns about a small increased risk of adverse heart effects in patients with type 2 diabetes treated with Avandia.
The research showed a small increased risk for heart attack and cardiovascular death among around 15,500 patients treated with Avandia.
The EMEA at the time pointed out that when Avandia was first introduced in EU countries in 2000, it was contraindicated in patients with a history of heart failure, and since then, the EMEA says it has kept the drug under close surveillance for adverse heart effects, including heart failure and other disorders including heart attack.
The EMEA last year updated the Avandia product information with information about the risk of cardiac ischaemic events (events linked to a lack of blood supply to the heart).
In May of this year, the agency advised doctors to adhere to the restrictions use of the diabetes drug in patients with heart disease.
The IMB stressed that it monitors the safety of all authorised medicinal products on an ongoing basis.
How Dr Reddy's chased diabetes molecule dream
Noemie Bisserbe, TNN
9 Aug, 2007 - Last week’s announcement by Dr Reddy’s Laboratories (DRL) that its anti-diabetes molecule Balaglitazone has entered the final phase of clinical development is not just a milestone in an Indian company’s journey to become a drug innovator, but also a strong comeback for a molecule that often stood at the doorstep of obscurity.
But if the page-turning history of Balaglitazone were to end in a marketable drug, the molecule must pass the clinical phase in a way that answers concerns over safety and side-effects which bog down the type 2 diabetes segment, industry observers say.
The story started in 1994, when the company initiated its discovery research programme. “We immediately identified diabetes as a major opportunity,” DRL chairman Anji Reddy recalled in an interview with ET.
While type 1 diabetes can be treated with insulin injections, a hormone that regulates the body metabolism, patients suffering from type 2 diabetes often develop a resistance to insulin. A decade ago, the medical fraternity didn’t have an answer. “Once we had identified the unmet medical need we wanted to address, we decided to start working on three different molecules, in the hope that at least one of them would make it to the market,” said Mr Reddy.
Balaglitazone was the first lead to come out of the company’s research lab. “Early trials showed that Balaglitazone sensitised the cells to insulin.”
Soon, the molecule became the first new drug out of Indian labs to be licensed out to a pharmaceutical giant. In 1997, the molecule was licensed out to Danish pharma major Novo Nordisk, as Dr Reddy’s wanted to mitigate the risks and costs involved in new drug development.
But the first threat for Balaglitazone came in the form of another molecule from Dr Reddy’s. “The same year, we came up with a second lead, Ragaglitazone. Ragaglitazone immediately appeared extremely promising. Not only did it sensitise cells to insulin like Balaglitazone, but it also helped reduce lipids.” As the molecule entered phase II of clinical development in 1998, Ragaglitazone was also licensed out to Novo Nordisk.
As Ragaglitazone’s therapeutic properties appeared superior to that of Balaglitazone, Novo Nordisk decided to suspend clinical development of the latter in favour of the new molecule.
Other companies had already attacked Balaglitazone’s drug class successfully. By 1999, Takeda and GlaxoSmithKline had already launched Actos and Avandia, respectively. These drugs, too, sensitised cells to insulin.
Just when Balaglitazone’s brief career appeared to have ended, Ragaglitazone hit a roadblock. In 2002, when the new molecule was about to complete phase III of clinical development, tumours were discovered in rats during long-term carcinogenecity studies. Ragaglitazone had to be buried.
Balaglitazone received a second look from Novo Nordisk, with resumption of clinical development after remaining in deep freeze for long. While similar drugs had already been launched in the market, side effects associated with the treatment of type 2 diabetes remained considerable. Balaglitazone could still make a mark if it can reduce the side effects associated with the treatment.
But the hope was short-lived. “Only a few months later, Novo Nordisk told us that they did not want to continue the development of Balaglitazone because they had decided to stop working on small molecules,” said Mr Reddy. According to analysts, Novo Nordisk was not entirely convinced by the results shown by the molecule in the initial phases of clinical trials. “I asked Novo Nordisk to at least complete phase II of clinical trials, for which I paid them $2 million, and they returned us the molecule in 2004.”
Rheoscience, also a Danish company, then took up the molecule and gave it a fresh lease of life. Under the tie-up with Dr Reddy’s, Rheoscience is responsible for financing clinical trials, expected to cost $50-100 million. In return, it will get marketing rights for the drug in Europe and China, while Dr Reddy’s will retain the marketing rights for the rest of the world, including the US and India.
Now in the final phase before launch, the new drug will be tested in over a thousand diabetes patients across Europe, Asia and the US. If all goes well, the drug could reach market in three to four years.
However, the recent debate on the safety of GSK’s Avandia has raised concerns over Dr Reddy’s ability to take Balaglitazone to the market, as it belongs to the same drug class. Recent safety data have shown that Avandia could potentially lead to a significant increase in the risk of heart attack.
“While Balaglitazone entering phase III of clinical trials is a very positive development, one needs to be conservative while estimating the drug’s potential,” a senior analyst told ET. “If the drug makes it to the market, it needs to be well accepted by the medical community.”
Dr Reddy’s has a back-up to Balaglitazone, just in case. The company is already working on a third diabetes lead molecule, code named DRL 16536, which is still in phase I of clinical trials.
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