U.S. advisers began weighing the fate of GlaxoSmithKline Plc's diabetes pill Avandia on Tuesday at a two-day meeting that will consider if the medicine is too dangerous to stay on the market.
The scientific experts assembled by the U.S. Food and Drug Administration will sort through sharply conflicting data on whether Avandia causes heart attacks.
Follow the science where it leads and the rest will fall into place, urged FDA Commissioner Margaret Hamburg in opening the meeting, acknowledging that the advisers had a difficult job.
The recommendations of the panel, with 33 voting members, are expected to weigh heavily on the FDA in making its final decision in the coming months.
British-based Glaxo could face a new wave of lawsuits if the drug comes off the market.
The pill was once Glaxo's second-biggest drug but its sales have plunged since safety fears erupted three years ago. Revenues totaled 771 million pounds ($1.16 billion) in 2009, equivalent to 2.7 percent of Glaxo's group sales.
Added pressure is coming from the European Medicines Agency, which has launched a new review into Avandia's risks and benefits.
For the FDA, the case is seen as a test of how the agency will handle major controversies under Democratic President Barack Obama. Officials are facing heavy pressure from consumer groups and some lawmakers who say the FDA fumbled decisions in past administrations and failed to protect the public.
Some staff see the Glaxo drug as more dangerous to the heart than Takeda Pharmaceutical Co's rival diabetes pill, Actos, with no unique benefits. Others remain unconvinced Avandia raises heart-attack risk. The current warning on the drug, added in 2007, says the data is inconclusive.
Glaxo has vigorously defended the medicine, based in part on a study called Record that found no higher rates of heart-related hospitalizations or deaths.
Company presenters were due to address the advisers shortly, followed by a parade of FDA staff and outside experts that will continue on Wednesday morning.
On Wednesday afternoon, the panel of cardiologists, endocrinologist and other experts will be asked to choose one of five options, ranging from keeping the drug on the market without a heart-attack warning to recommending a withdrawal. Restricting use or beefing up warnings are other choices.
Dr. Janet Woodcock, head of the FDA's drug division, told reporters at a briefing ahead of the advisory panel meeting that many drugs faced scrutiny in the past for risks that later proved untrue. She pointed to calcium channel blockers, widely used heart drugs that were tied to heart disease, cancer and other problems in the 1990s. Later studies concluded those risks did not exist, she said.
Some doctors want to keep Avandia as an option for lowering blood sugar when other medicines do not help. Without blood sugar control, diabetics can suffer heart disease, limb amputations and other serious complications.
The Avandia decision rests on which of many studies the panelists view as stronger. All have strengths and weaknesses.
Glaxo says six randomized clinical trials, considered the gold standard of medical evidence, showed Avandia did not raise the overall risk of heart attack, stroke or death.
But the company's Record trial has come under sharp attack from an FDA heart expert who concluded it was inadequately designed to rule out cardiovascular risk.
Dr. Thomas Marciniak, a medical team leader in the FDA division that reviews heart drugs, added in briefing materials released last week that biases in the study suggest that the true risk (of heart attack) could be higher. Marciniak is due to address Tuesday morning's session of the meeting.
Other FDA staff said the study backed Avandia as safe.
An ongoing study comparing Avandia and Actos could provide a more definitive answer but critics argue it is wrong to wait years for those results. They say findings against Avandia are strong enough now to warrant the drug's removal.
Still more data could emerge from lawsuits against Glaxo, but it is unclear if a U.S. court will allow the release of documents in time to be included in the FDA's decision.
(Reporting by Lisa Richwine; Editing by Tim Dobbyn)