Fourteen years after AstraZeneca’s blood thinner Brilinta reached the market and now faces generic competition, the data that backed its original approvals around the world has been called into question.
In December, the U.K. medical journal BMJ found data integrity problems with the pivotal phase 3 Plato trial, which indicated Brilinta’s superiority to Bristol Myers Squibb and Sanofi’s anticoagulant Plavix.
Seven months later, after an expanded investigation, the BMJ has uncovered inaccuracies in two other supporting studies, which helped convince physicians of Brilinta’s ability to inhibit platelets.
“The (new) findings raise even deeper questions over the approval and decade-long use of the drug,” the BMJ wrote in an article Thursday.
The primary endpoint data for the supporting trials—dubbed Onset/Offset and Respond—were reported inaccurately in the cardiovascular-focused scientific journal Circulation, the BMJ found. Additionally, more than 60 of 282 readings from platelet machines used in the trials were eliminated from FDA datasets, the publication discovered.
The BMJ questioned the competence of several trial sites involved in Onset/Offset and the integrity of the data they provided, pointing to some missing patient baseline data and unusual platelet aggregation patterns that appeared to be “an improbable effect for an anti-platelet drug.”
The BMJ also found that one trial investigator was not included as a study author, while another investigator denied his involvement in the trial.
“Most investigators, including the principal investigator, were unreachable or declined to be interviewed,” the BMJ added.
AZ did not respond to a request for comment from the BMJ during its investigation, but a spokesperson did tell Fierce Pharma on Monday that “we are confident in the integrity of the trials and its evidence in support of Brilinta/Brilique.”
Brilique is the P2Y12 receptor antagonist’s commercial name in Europe.
AZ made a huge investment in Brilinta after its blockbuster statin treatment Crestor lost its exclusivity following its sales peak of $6.6 billion in 2011. Brilinta maxed out its sales at $1.6 billion in 2020, but its momentum was slowed by results from two studies in 2016. In one, Brilinta failed to top aspirin in preventing strokes. In the other, it came up short in comparison to Plavix at preventing major adverse cardiac events.
Brilinta’s sales growth later took a hit during the COVID-19 pandemic as heart-related hospitalizations plummeted. A price-cutting scheme in China called the volume-based procurement (VBP) program also hindered sales. Last year, AZ reported revenue from Brilinta had shrunk to $751 million.
According to the FDA's Orange Book, Brilinta's patent exclusivity expired in the U.S. in May, with its pediatric market exclusivity stretching into November of this year.