FDA caution hurts GSK's Advair drug

Doctors told of asthma complications

The Food and Drug Administration has urged physicians to restrict the use of Advair and recommended stronger warnings be added to its packaging, saying GlaxoSmithKline's popular asthma medicine increases the chance of deadly complications from the respiratory disease.

Surprised analysts predict the regulatory proposals would slow Advair sales growth in the short term, which could hurt GSK's outlook on Wall Street. The disk-shaped, purple-and-white inhaler that dispenses two powerful chemicals is the British drug maker's best seller. Last year, it generated about $4.5 billion in sales, more than half in the United States.

Several local physicians said there aren't good alternatives to Advair and that they plan to continue prescribing the treatment.

Still, the FDA's announcement clearly spooked investors. GSK's American depositary receipts, which are similar to stock, closed at $49.16 Monday, down nearly $3 since Friday, when the FDA released its recommendations.

GSK, which has a U.S. headquarters in Research Triangle Park and produces U.S. supplies of Advair at its facility in Zebulon, disagreed with the FDA's proposed changes, saying they were a departure from a favorable regulatory finding just four months ago.

In July, an FDA panel recommended that Advair and two other asthma medications remain on the market without additional restrictions. The panel had urged that the three medications be tested further to see whether they worsen the disease in certain patients. But no new research data has become available.

"We're trying to understand where this is coming from," said Dr. Kathy Rickard, GSK's vice president of clinical development and medical affairs for respiratory medicines in the Unites States.

GSK plans to talk with FDA officials, Rickard said, to determine "which direction we'll be going."

The drug maker is expected to respond within about 30 days. But it's unclear when or whether any actions will be taken, she said.

Analysts suggested that regulators are under political pressure after the Vioxx debacle, when they were slow to react to warning signals that the painkiller increased the risks of heart attack and stroke.

"Clearly they're sensitive at the moment," said Martin Hall, a pharmaceutical analyst with Eden Financial.

FDA officials could not be reached for comment Monday.

Regulators fingered Advair, Serevent and Foradil, three asthma medications containing beta-agonists, chemicals that relax the muscles around airways to keep them open. Foradil is sold by Swiss drug maker Novartis. Advair and Serevent are GSK drugs.

Available since 2001, Advair contains a steroid to reduce inflammation and a beta-agonist called salmeterol. Salmeterol also is the active ingredient in Serevent, which has been on the market since 1994.

In 2003, after enrolling 26,000 patients, GSK stopped a Serevent study early. Preliminary data showed that Serevent users risked a small but significant increase in asthma-related deaths, compared to patients receiving a dummy drug. African-Americans were particularly vulnerable, but the study was not designed to explain why.

Final results of the study have never been published, and GSK has said that stopping the study was unrelated to safety issues.

Shortly after the FDA announced the risks from the preliminary Serevent data in 2003, the consumer watchdog group Public Citizen put Serevent on its list of worst drugs. After Vioxx raised questions about drug safety last year, an FDA official in testimony to Congress listed Serevent as one of five drugs he considered dangerous.

GSK has maintained that risks associated with Serevent didn't affect Advair, because Advair also contains a steroid. None of the Advair studies showed the combination drug carried risks similar to Serevent, GSK's Rickard said.

More information about Advair's risks may become available next year, when GSK is expected to release results from the first study looking at death rates.

Meanwhile, Dr. Craig LaForce of Carolina Allergy & Asthma in Raleigh plans to keep giving Advair to patients.

"The number of people it helps is so large and the number of people at risk is so vanishingly small," LaForce said. "This warning doesn't change our prescribing" habits.