By Ben Hirschler
LONDON (Reuters) - The U.S. government has cleared AstraZeneca Plc over a major clinical trial used to win marketing approval for its important new heart drug Brilinta, following an investigation which had cast a shadow over its prospects.
The drugmaker said on Tuesday the Department of Justice (DoJ) was closing the probe into the 18,000-patient study and no further action was planned.
AstraZeneca views Brilinta as a potential $3.5 billion-a-year seller, but news last October that the DoJ was quizzing the company about the way it conducted the trial raised doubts over its medical value, causing sales growth to stall.
"It's frustrating to think of the patients who probably should have been receiving Brilinta for the last nine months but potentially didn't because of this cloud hanging over the brand," Tom Keith-Roach, vice president for the drug, told Reuters.
"I think physicians, particularly in the U.S., will now see that a line has been drawn underneath any potential controversy surrounding the trial."
The DOJ move was highly unusual. The department has traditionally focused on potential marketing misconduct by drugmakers, rather than looking into the underlying data behind the granting of a license.
Concerns triggered by the probe had also knocked confidence among some heart doctors in Germany and Australia.
AstraZeneca flagged up the promise of Brilinta in its defense against an abortive $118 billion takeover bid by Pfizer Inc earlier this year, although the drug registered only modest sales of $216 million in the first half of 2014.
AstraZeneca also reported positive results on Tuesday with an experimental antibiotic called ceftazidime-avibactam as a treatment for hospitalized adult patients with complicated intra-abdominal infections.
Both pieces of news will be welcomed by Chief Executive Pascal Soriot, who is determined to prove AstraZeneca has a strong independent future after fending off Pfizer. Many analysts believe Pfizer could repeat its bid to buy AstraZeneca later this year.
EASTERN EUROPEAN PATIENTS
The results of the so-called PLATO study into Brilinta were first reported at a medical meeting in 2009 and went on to form the basis of successful new drug applications in the United States, Europe and other markets. Brilinta was launched in 2011.
But various aspects of the study, which relied heavily on patients recruited in eastern Europe, have been criticized over the years by a number of medical experts. Poland and Hungary together accounted for 21 percent of all subjects studied - more than double the United States and Canada combined.
Two doctors, James DiNicolantonio of Ithaca, New York and Ales Tomek of Charles University in Prague, raised several questions about the conduct of the study in a paper in the International Journal of Cardiology last year.
In particular, their analysis found that patients in the PLATO trial who were monitored by AstraZeneca were reported as having more beneficial effects from taking Brilinta than those monitored by an independent clinical research organization.
However, Lars Wallentin of Uppsala Clinical Research Center in Sweden, the principal investigator on PLATO, strongly defended the integrity of the study and AstraZeneca has always insisted it is confident in Brilinta's profile.
NEW USES FOR MEDICINE
AstraZeneca's 2023 estimate for Brilinta sales of $3.5 billion assumes the blood-thinning drug works in a variety of other settings beyond its current indication for acute coronary syndrome.
A major development program by the company is now under way to prove the case, with a series of new clinical trials expected to report results every year between 2015 and 2018.
Demonstrating Brilinta's unique value in multiple groups of heart patients is crucial for commercial success, since the product is competing with Sanofi SA's now off-patent medicine Plavix, which is available as a cheap generic.
Keith-Roach said AstraZeneca hoped to report headline results from one of these trials, known as PEGASUS, in December, before presenting full findings from the 21,000-patient study to a medical meeting in 2015.
PEGASUS is assessing the use of Brilinta in patients who experienced a heart attack 1-3 years ago. If successful, this group could more than double the number patients eligible to receive the medicine.
Shares in AstraZeneca were 0.8 percent higher at 0950 GMT (5.50 a.m. EDT), slightly outperforming a 0.4 percent rise in the European drugs sector.
(Editing by David Holmes)