AstraZeneca’s Brilinta May Be Cleared

AstraZeneca Plc’s blood-thinner Brilinta is approvable if the drugmaker undertakes a study on its effectiveness in Americans after it’s marketed, staff from the U.S. Food and Drug Administration said today.

The new study would be designed to establish the drug’s long-term benefit after earlier testing in North America fell short of results seen elsewhere. Brilinta, a possible rival to Bristol-Myers Squibb Co. and Sanofi-Aventis SA’s Plavix, is used to reduce heart attacks and strokes.

AstraZeneca, the U.K.’s second-largest drugmaker, needs to replenish revenue over the next four years as patents expire on its top-sellers, Nexium for heartburn and the anti-psychotic Seroquel. The drugs generated a combined $9.83 billion in 2009. Brilinta sales could reach $1.47 billion by 2016, according to the average estimate of three analysts surveyed by Bloomberg.

”A lot of drugs end up getting approved with post- marketing commitments, so this is absolutely what should have been expected from day one,” said Gbola Amusa, a UBS AG analyst in London, in a telephone interview. “This could be the new standard of care.”

American depositary receipts for London-based AstraZeneca rallied after the staff report suggested a route to approval. The ADRs, each representing one ordinary share, gained $1.89, or 3.9 percent, to $50.51 at 4:15 p.m. in New York Stock Exchange composite trading.

Meeting This Week

FDA advisers meet July 28 to weigh whether to support Brilinta’s approval. The drug would compete with Plavix, the world’s second-biggest drug, and Effient, from Eli Lilly & Co.

All three are pills designed to prevent platelets in the blood from clumping together to form clots. Plavix and Effient are both taken daily and remain effective for one week after treatment is halted. Brilinta, taken twice daily, wears off more quickly. All three pills increase bleeding risk with surgery.

“In all these drugs there’s a tradeoff in effectiveness and bleeding,” said David Pearle, a cardiologist at Georgetown University Hospital in Washington, D.C., in a July 21 telephone interview. “Brilinta it turns out may be a little bit closer to the sweet spot than either Plavix or Effient. In other words, we want just enough platelet blockage to be effective but no more bleeding than is absolutely necessary.”

Plato Study Results

In the key company-funded study called Plato, 18,624 patients got Brilinta or Plavix for a year after being treated for a heart attack or worsening chest pain. With Brilinta, 9.8 percent of patients had a heart attack, stroke or died from cardiovascular disease. That compared with 11.7 percent for those on Plavix, according to data published in August 2009. Death from all causes was 4.5 percent with Brilinta and 5.9 percent with Plavix.

Life-threatening bleeding occurred in 11.6 percent of Brilinta patients and 11.2 percent on Plavix, though the difference wasn’t statistically significant.

About 13 percent of the patients lacked data to determine whether they had a heart attack, stroke or death from cardiovascular causes, said Thomas Marciniak, the FDA’s medical team leader, in a memo to the advisory panel included in the staff report. That raises questions about the integrity of data suggesting long-term benefit with Brilinta, chemically known as ticagrelor, he said.

“Given the incompleteness of follow-up, are the results real?,” Marciniak wrote.

Differences by Country

The results also indicated that Brilinta seemed to be worse than Plavix for study participants in the U.S. and Canada. AstraZeneca has suggested that higher aspirin use in the U.S., compared with other regions where Brilinta was tested, may have contributed to that unexpected outcome.

FDA reviewers examined this issue and determined that timing of dosing in the U.S. and a potential delayed onset of Brilinta may explain the discrepancy better than use of aspirin.

“The Office of Clinical Pharmacology has reviewed the submission and cannot resolve the differential effectiveness of ticagrelor in U.S. and non-U.S. sites,” FDA staff said in their report. “Given the overall results, the Office recommends approval of ticagrelor with a study post-approval aimed to reconcile the findings from U.S. region.”

Dosing Concerns

The Plato trial also pitted Brilinta primarily against a 300-milligram dose of Plavix, half the standard dose used in the U.S. since 2007, said Amit Roy, an analyst with Nomura International Plc in London, in a July 15 research report.

“We do not expect a major impact of Brilinta on current medical practice,” Roy said. Brilinta may struggle to gain market share, as occurred with Effient, also tested against a 300-milligram Plavix dose, Roy said.

Plavix had $9.8 billion in sales last year for New York- based Bristol-Myers and its marketing partner, Sanofi of Paris. The drug, chemically known as clopidogrel, is set to lose patent protection in 2011, opening the market to lower-cost generic copies.

Effient, approved in July 2009, had sales of $27 million last year for Lilly, based in Indianapolis, and its marketing partner Daiichi Sankyo Co. of Tokyo. The pill, also called prasugrel, was cleared with a warning of bleeding risk.

About 733,000 hospitalizations in 2006 were credited to heart attacks and chest pain, representing a “conservative estimate” of the prevalence of acute coronary syndromes, according to the American Heart Association. While Plavix, introduced in 1997, helps lower subsequent risks, cardiovascular disease remains the leading cause of death worldwide.

The FDA is scheduled to decide on Brilinta by Sept. 19. The agency usually follows the recommendations of its advisory panels, though it isn’t required to do so.

Lipitor, made by New York-based Pfizer Inc., is the world’s best-selling drug with 2009 revenue of $11.4 billion. GlaxoSmithKline Plc is the biggest U.K. drugmaker and, like AstraZeneca, is based in London.

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