Mumbai based Sun Pharmaceuticals is allegedly promoting its branded letrozole (Letroz), an expensive anti-cancer drug, for indications for which it has no approval from the Drugs Controller General of India (DCGI). While DCGI has given marketing sanctions for Letroz to be used as a breast cancer drug for menopausal women, the company is known to be promoting it also as an "anti infertility drug".
As part of promoting the product as a drug for the "unapproved indication", Sun Pharmaceuticals has in the past several months conducted seminars titled "Newer drugs in infertility" across the length and breadth of the country.
According to medical experts, the company is treading a dangerous path as the drug is acknowledged to be embryotoxic (toxic to eggs) and fetotoxic (harmful to foetus) by the original discoverer as well as drug regulators around the world including the U. S. Food & Drug Administration (USFDA), the British Medicines and Healthcare products Regulatory Agency (MHRA) and Australian Therapeutic Goods Administration (TGA).
Letrozole, a research product of Novartis, is globally approved for use only in post-menopausal women afflicted with breast cancer. The drug is not approved for any other use anywhere in the world. Letrozole was approved by US FDA for cancer therapy in January 2001. Even before the drug was cleared, a couple of researchers had experimentally tested the drug in a few female patients of Polycystic Ovary Syndrome (PCOS) to see its effect on ovulation. These preliminary, observational trials conducted in a research setting were merely meant to test a new theory. It is known that Sun Pharmaceuticals had been depending on these studies to promote the drug for its "new use".
In a communication to a medical publication here, the lead researcher who conducted these observational trials has said that their theory is yet to be confirmed by a series of "definitive, randomised, prospective, placebo-controlled studies of efficacy."
The lead researcher Dr. Robert F. Casper has informed that no controlled trials, acceptable to regulatory agencies (such as USFDA) have been conducted so far any where in the world and no country, particularly in the West has permitted the use of letrozole in female infertility. He has also stated that "while some experimental studies are underway there will be no results for several years."
It is learnt that even if the researchers' theory is ultimately found to be valid, it will be applicable to a few, specific, selected cases of WHO Type II infertility. "Women with WHO Type I and III infertility are not likely to benefit," according to researchers. Furthermore the hypothesis will need to be tried and tested in thousands of women in confirmatory (Phase III) multi-centre trials before it is even considered, let alone approved, by drug regulatory authorities anywhere in the world for use in infertile women.
However, the printed literature supplied by Inca Specialties, a division of Sun Pharmaceutical Industries Limited calls "Letroz" as a new perspective in "ovulation induction". The company literature claims " Letroz is a specific, reversible, nonsteroidal aromatase inhibitor that suppresses estrogen biosynthesis. Letroz has no effect on estrogen receptors unlike CC (clomiphene citrate, a common fertility drug) and thus does not cause ER down regulation. Hence Letroz is free from adverse effects on endometrium and cervical mucous. In the letrozole treated cycles, endometrium is of adequate thickness as compared to CC. All these effects improve pregnancy rate eg: The pregnancy rates observed with letrozole are 16.7% as compared to CC 5.6 %."
As per the D&C Act, if a drug cleared for a specific disease is to be used for a new disorder, the drug is considered a "New Drug" (as defined in Rule 122-E in the Drugs and Cosmetics Rules) and needs fresh government approval after undergoing a series of tests and trials, both in animals and humans. Only then can it be marketed and promoted for a new disorder. No such trials have been undertaken on letrozole's use as a fertility agent.
If the drug is to be tested in Indian patients for uses other than breast cancer, the sponsors will need to procure prior, mandatory DCGI approval, obtain permission from the Hospitals' Ethics Committees, conduct trials in recognized hospitals with research facilities, inform the patients that they were being subjected to experiments with uncertain outcome, obtain written "Informed Consent", and undertake to compensate patients in case of any untoward effects. Failure to comply with these mandatory legal requirements can result in penal action against both, the sponsors and investigators.
Being a new drug, letrozole will need intensive post-marketing surveillance the world over in breast cancer patients for years before its effects and adverse effects are fully known. According to experts, new side effects needing dose reduction and even withdrawal are encountered in about 80 per cent of cases of new drugs. Promoting the use of such an untested drug in healthy, young women without regulatory approval is not only illegal but also patently unethical, they opine.
When contacted senior officials at the office of the DCGI informed that they are yet to receive any complaints regarding the illegal promotion of the drug.