Mumbai: A cardiac risk associated with Pfizer Inc.’s newly launched kidney cancer drug Sutent may trigger a regulatory review of the product that was launched in January in India.
The India launch was based on global data on the drug’s performance and side effects, but a month after this, a small study in the US reported a disproportionately high number of heart failures among its users. The drug was launched in the US in Miami, Florida, on 20 March 2006.
The office of India’s drug regulator, the drug controller general of India (DCGI), is yet to call for a review of the drug, but experts here say that considering the high risk, reported as 15% in the study, the drug should be subjected to a risk-benefit analysis.
The country’s former drug controller general, M. Venkateswarlu, under whose reign this drug was approved in India, said: “In case of more adverse reports coming during post-marketing, the regulator would normally redo a risk-benefit analysis and the product will be recalled if the risks are higher than the benefit, and if it is the other way, the product may still be continued with caution.”
Pfizer, the world’s top research spender, said “cardiovascular events” have been observed with Sutent and are included in the approved product labelling with recommendations for monitoring in patients with cardiac risk factors.
A Pfizer spokesperson said nearly half the patients in the latest study had pre-existing hypertension, a cardiac risk factor. A history of congestive heart failure, coronary artery disease and low body mass index were factors that appeared to be associated with increased risk from the drug.
Sutent, also known by its chemical term sunitinib malate, is prescribed for patients with advanced kidney and stomach cancer.
The study by a team of US researchers, published in the first week of February, said seven of 48 patients who took the drug, or nearly 15%, developed heart failure. Adverse reaction in 8-15% of the patients is considered high in a normal drug risk-benefit analysis.
A senior official at India’s Central Drug Controls Standard Organization, who did not want to be identified, said: “The department has not heard any adverse instances from Pfizer and the department may act appropriately if there are any.”
The organization prescribes standards for drugs and cosmetics in the country.
Certain drugs are approved in India without clinical trials if they are of a life-saving nature and needs of patients are of an immediate nature. As a result, the adverse reactions of such drugs are not immediately known and approvals are based on global data available, Venkateswarlu said.
In May 2007, the US Food and Drug Administration, the country’s drug regulator, had approved safety labelling revisions to advise of cardiovascular and other risks associated with the drug; the agency is yet to respond to the recent study. Sutent was originally approved in January 2006.
Pfizer said it is working with the authors of the study so it can better understand the underlying biological mechanisms leading to these events and develop strategies for prevention and treatment.
Previous studies had suggested that the drug caused risky but reversible side effects. Sutent was shown to damage heart cells.
Cancer specialists in India are not too worried about the recent findings. Though some such as Dr Chandra Gulhati believe it is very likely that cases of serious adverse reactions to Sutent will emerge in India as well, doctors treating the condition said the risks will not significantly hurt the use of the drug.
“While we do agree that the potential side effects are serious, we have to view these in light of the seriousness of the disease that it is used to treat,” said Dr Avinash Deo, medical oncologist (or cancer specialist) at LH Hiranandani Hospital in Mumbai. “Obviously the same side effects in a headache pill would be absolutely unacceptable, but when you are using the drug to treat a cancer that has few other treatment options, the benefits usually outweigh the risks.”
In the case of British drug major GlaxoSmithKline Plc.’s diabetes drug Avandia, which, too, was reported to increase the risk of cardiac problems, regulators permitted the drug to be continued in the market following a risk-benefit analysis despite adverse reports.
However, US drug firm Merck and Co. had to withdraw its blockbuster arthritis drug Vioxx in 2004 after a high incidence of adverse reactions.
According to Pfizer, more than 33,000 patients have been treated with Sutent in clinical settings and trials globally.
The number of patients using Sutent in India could not immediately be ascertained. The drug is very expensive here with a price tag of around Rs2 lakh for a course of one-and-a-half months.
S.H. Advani, a medical oncologist at the Asian Institute of Oncology at SL Raheja Hospital and Research Centre, Mumbai, said he has seen a good response to the use of the drug. “There are few drugs that are as effective in treating metastatic renal cell carcinoma (cancer of the kidney cells), so we do prescribe this drug quite a bit,” he added. “The drug is very prohibitively priced so most patients cannot afford it, said Chetna Bakshi, medical oncologist at Wockhardt Hospitals in Mumbai
Dr Advani said he is yet to come across serious side effects for the drug yet: “Most of the side effects I see in my practice are limited to skin rashes and diarrhoea, and hand and foot syndrome where the hands and feet turn black but almost all these are reversible. The benefits surely outweigh most of the risks.”
Pfizer’s spokesperson said the company has developed a Sutent Patient Assistance Program, recognizing that not too many people here may be able to afford the drug. “Sutent is currently priced in the same range as other oncology drugs in its class in India. Depending on the patient’s eligibility, there is a three-tiered pricing structure ranging from Rs1.96 lakh for one-and-a-half months to free of charge,” the spokesperson added.
The cancer the drug treats is relatively uncommon in India. “I saw almost 1,500 patients in the last year and out of these, there were only three cases of metastatic renal cell carcinoma,” Dr Bakshi said.