New Delhi: Indian pharma firms developing oral anti-diabetes drugs and targeting the US market are likely to spend more time and money than they would have budgeted for before their drugs get regulatory approvals.

These companies, including Dr Reddy’s Laboratories Ltd (DRL), Piramal Life Sciences Ltd, Biocon Ltd and Glenmark Pharmaceuticals Ltd, will have to follow new 17 December recommendations by the US Food and Drug Administration, or FDA, and prove that their drug therapies for type 2, or adult onset, diabetes would not increase cardiovascular risks.

New roadblock: Dr Reddy’s research laboratory in Hyderabad. The company is likely to be affected by the new US guidelines. Bharat Sai / Mint

“We need to better understand the safety of new anti-diabetic drugs. Therefore, companies should conduct a more thorough examination of their drugs’ cardiovascular risks during the product’s development stage," Mary Parks, director, division of metabolism and endocrinology products, center for drug evaluation and research, FDA, said in a press release.

“This will obviously cause delays in getting the drugs to the market. Pharma companies will have to undertake additional studies and conduct rigorous tests to prove that there is no cardiovascular implication," says Hitesh Gajaria, executive director, KPMG India Pvt. Ltd, that provides consultancy services.

In October, the American Diabetes Association and the European Association for the Study of Diabetes advised against the use of rosiglitazone due to its cardiovascular implications. The Indian drugs regulator also issued a warning on the drug in India. Rosiglitazone belongs to the glitazone class of oral diabetic drugs.

Balaglitazone, DRL’s lead molecule, which was termed as being closest to an Indian company’s new drug molecule launch in the market, belongs to the same class.

Projected to hit the market in 2011, balaglitazone has often been in troubled waters. In October 2004, Danish pharmaceutical firm Novo Nordisk AS terminated further clinical development of balaglitazone as pre-clinical results did not suggest a sufficient competitive advantage for the candidate compared with existing drugs.

More recently, as reported by Mint on 5 October, Danish firm Rheoscience AS, which is conducting phase III human clinical studies on the molecule, ran into a financial crisis.

“DRL has known for a few years now that its drug candidate balaglitazone is not very promising. But it has tried to hide this fact and gone ahead with developing the drug," said an industry insider on condition of anonymity. “They are most likely to suffer under the new recommended FDA guidelines."

A DRL spokesperson was unavailable for comment.

Piramal Life Sciences is developing two anti-diabetic compounds. The company has filed an investigational new drug application for one to start clinical trials. The other, P1201, is in phase I clinical trial stage.

Biocon’s oral insulin compound is in its phase II clinical trials, while Glenmark is scouting for partners to license out its phase II candidate melogliptin.

Glenmark is optimistic about its compound. “The final guidelines (of the FDA) are consistent with the earlier draft...released in March. These guidelines are recommended, not absolute requirements. To the extent applicable, we have taken into account these recommendations to develop melogliptin," says Glenn Saldanha, chief executive and managing director of Glenmark. “We do not anticipate any change in the expected launch timelines for our diabetes molecule."

However, Ranjit Kapadia, head of pharmaceutical research at investment consultancy Prabhudas Liladhar, is of the opinion that if at any stage, the results of a study do not fulfil FDA requirements, firms would have to conduct further studies, and invest more in volunteers.

“We will have to conduct further studies, which makes the process more expensive and long," agrees Swati Piramal, director and chief scientific officer, Piramal Healthcare. “Diabetes, in this sense, is different from other therapeutic areas because you have to look for side effects for a longer period of time and conduct studies on almost 20,000 patients as compared to 500 patients for cancer. This is why our primary focus has been cancer."

KPMG’s Gajaria says the new FDA suggestions are as good as binding on Indian firms wanting to sell new anti-diabetes drugs in the US.

“For the entire process since drug discovery to development through various clinical stages to marketing, it costs big pharma close to $1.2 billion (about Rs5,820 crore today). For Indian companies, however, which haven’t really gone beyond phase II on their own, this cost is somewhere between Rs30 crore and Rs100 crore. At this stage, Indian companies out-license their molecule since they don’t have the financial capabilities to take it through further stages," says Sujay Shetty, head of life sciences at consultancy PricewaterhouseCoopers. “When you look at conducting clinical trials that follow US FDA guidelines, you are looking at almost 60-70% of the entire cost. And particularly, the phase III is the most expensive since it requires thousands of volunteers. So, of that 60-70%, about 60% is spent in phase III alone."

The FDA guidance, effective immediately, defines more robust and adequate design and data collection approaches for phases II and III clinical trials than previously required.