Novo Nordisk India Private Limited categorically refuted the allegations that the clinical trials of ragaglitazar (NN622) have been conducted in an illegal or unethical fashion. In a press meet here this morning, Dr. Anil Kapur, managing director, Novo Nordisk India said that the charges are totally unfounded, baseless and these trials have been done to the 'highest ethical and scientific standards".

The clinical trials of ragaglitazar (NN622) that was stopped on July 22, 2002, in response to the findings of the urine bladder tumours in one mouse and a number of rats has led the company to an unprecedented crisis where its share price fell by 18 per cent on a single day. "Although it hit the company, still we decided to announce findings on rats". The clinical studies were done according to internationally accepted Good Clinical Practise (GCP) guidelines, informed Dr. Kapur. The cost of the research project was worth half billion Danish crone.

The suspension of drug trials will not affect the financial statement as inflow of income from the drug was expected only in 2005-2006. Now Novo Nordisk will look into the available data and go back for animal studies in consultation with external consultants. The chances of reaching the market are too early to predict and by Q1 2003 a decision will be taken to this effect.

A total of 2,500 patients in the age-group of 18-80 years in 32 countries including USA, several countries in Europe and Asia participated in the clinical trials being run by Novo Nordisk using similar trail design, protocols, standard operating procedures (SOPS) and safeguards, whether demanded by local law or not. India was one of the countries that participated in the Phase 3 clinical development programme. Around 8 centres in India were a part of the trials where 130 patients underwent the Phase 3 tests, Dr. Kapur said that none of the patients have withdrawn their consent from the trials, instead they have accepted the revised Informed Consent.

The studies received approval in all countries based on internationally accepted as well as domestic laws and guidelines governing such trials. These include regulatory authorities such as the US Food and Drug Administration, European health authorities and International Harmonisation Conference (ICH) guidelines, said Dr. Kapur.

Adequate short term studies as well as long-term animal toxicity studies indicating safety for human use as required by these agencies including schedule Y of the Indian Drugs and Cosmetics Act, at a current stage of the development of the drug, were provided when the trials were approved, he added.

Of the 2,500 patients enrolled in the clinical development programme worldwide, about 1,100 participants received ragaglitazar, while others received an anti diabetic medicine. Some participants also received placebo tablets as is normally done in Phase 3 trials. In India, about 130 participants participated in the clinical development and approximately half of them received the active drug whereas the remaining received another already marketed anti diabetic drug for comparison purposes. The maximum exposure in any of the clinical studies is about 6-7 months, while in India the maximum exposure was approximately 4 months when clinical trials were stopped.

The company decided to suspend the trials immediately after learning that one single mouse treated with ragaglitazar for almost two years developed urine bladder tumour. Early this year similar findings were found in similar rats. Dr. Kapur averred that many pharmaceutical products in the market today have shown to cause tumours involving rats.

Novo Nordisk is investigating the available information, the questions of whether the people who received the study drug are at any risk of any similar developments. "But the risk of tumours in human beings is extremely low. However, being a responsible company, Novo Nordisk decided to stop all trials and the patients will be followed up for one year period," said Dr.Kapur.

The animals that have developed tumours were exposed for almost half to all their lifespan, while human beings in the studies received the drug on an average for 6-7 months (in India for no more than four months) which is about 0.5 per cent - 1 per cent of the average life span.

The fact that simultaneous clinical studies in India were done in the same phase as in USA and Europe indicate confidence that Novo Nordisk has in Indian research and its ability to perform GCP studies. "It is a matter of pride that a promising Indian drug discovery reached Phase 3 clinical studies. Although the current status is a set back, it does not reduce Novo confidence in Indian research, said Anne Bording Jensen, project director, ragaglitazar research, Novo Nordisk, Denmark in a video conferencing session with the press.

On whether there would be any lawsuits filed, Dr. Kapur and Bording Jensen said that since they were very clear that they followed practise and patients have been informed about the risk and the risk of developing any complications is extremely remote.