The Indian edition of Monthly Index of Medical Specialties (MIMS) has accused the Drugs Controller General of India (DCGI) of violating drug laws in allowing Sun Pharma to market letrozole, a breast cancer medicine prescribed for post-menopausal women, for infertility treatment. The latest issue of the magazine says the drug did not undergo mandatory clinical trials and it is the first time the DCGI is approving a drug for a disorder for which it is not approved anywhere else in the world.
Letrozole, a research molecule of Novartis, is indicated for use in cases of breast cancer in post-menopausal women all over the world. Though Sun is among several Indian companies that manufacture and sell the copycat version of letrozole, only Sun promotes it as an infertility drug.
Sun Pharma denied any wrongdoing. “The drug has been approved by the DCGI after meeting all regulatory requirements of the country. We are not aware of any lapses in the procedure that we have followed”, said a Sun spokesperson.
Refuting the claim, MIMS editor and medical expert CM Gulhati said the company did not conduct any of the early-stage clinical trials mandated under the law.
“As per the Drugs and Cosmetics Rules, even an old drug, when used for a new indication, must undergo a series of safety and efficacy studies both in animals and humans before its use in general public is allowed. If the drug is intended for use in young women of child-bearing age, reproductive studies must be performed in two female animals such as mouse, dog or rabbit. The drug must also undergo Phase-I clinical trials in about 10 healthy volunteers (pre-menopausal women over 18 years of age) to determine the maximum tolerated dose and to document the preliminary side effects. Exploratory Phase-II studies to determine the therapeutic use, dose and safety of the drug are to be conducted in 10-12 patients each in three-four research hospitals. None of these studies were done”, Gulhati said.
The drugs control officials said the approval was given in April 2007 after Sun submitted clinical-trial reports and international research findings. According to a senior official, results on clinical trials carried out on 55 patients were submitted.
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“Moreover, since this drug is meant to be used for only five days in a cycle for induction of ovulation for a maximum of three cycles, the incidence and severity of its side effects is anticipated to be much less compared with its months-long use in breast cancer”, he said.
“The Phase-III trial, involving just 55 patients, is too small to arrive at any conclusion. As per the Indian rules, the drug should have been tested on a minimum of 100 patients,” Gulhati said, adding, “The trial was conducted by private practitioners in personal clinics while such studies should be conducted by independent, experienced investigators in large research hospitals attached to medical colleges”.
According to Gulhati, “The principal investigator of the trial, a Mumbai-based gynaecologist, was caught red-handed in 2003 along with a dozen other gynaecologists for conducting illegal trials of letrozole sponsored by Sun Pharmaceuticals”.
“A complaint against all self-styled ‘researchers’ for indulging in illegal activities and professional misconduct is pending in the Medical Council of India. In 2003, the company was also caught illegally promoting letrozole for infertility. Instead of blacklisting the company, its application, dated October 17, 2003, requesting permission to conduct clinical trials, was accepted. Ultimately, the offending company was rewarded with an unprecedented permission to market a globally-prohibited drug to young females in India”, Gulhati said.
Novartis, which holds patents on letrozole and globally markets the medicine under the Femara brand, said it did not believe there was adequate well-controlled data to support regulatory approval to the use of letrozole to treat infertility. “In the absence of such clinical data, the use of letrozole in such a manner may put patients at risk,” Ranjit Shahani, managing director Novartis India Ltd said, adding that it was highly inappropriate for any third party to comment on a decision by the office of the Drugs Controller General of India.”