AstraZeneca has been boosted by the news that the US government has closed its investigation into a Phase III trial that formed the basis for the approval of its closely-watched heart drug Brilinta and will take no further action.
Last October, AstraZeneca received a civil investigative demand from the Department of Justice seeking documents and information related to the 18,624-patient PLATO trial. Data from the latter led to a US Food and Drug Administration green light in 2011 for Brilinta (ticagrelor) for acute coronary syndrome and the drug has now been approved in over 100 countries.
However, certain aspects of the study, which established the superiority of Brilinta over Sanofi’s Plavix (clopidogrel) had been criticised in some quarters. Concerns included difference in treatment effect observed in the US and non-US patient subsets (Poland and Hungary accounted for 21% of patients evaluated) and a paper published in the International Journal of Cardiology last year, which alleged “multiple serious deficiencies” in the PLATO data.
AstraZeneca chief executive Pascal Soriot said the firm welcomes the DoJ’s decision not to pursue further action, noting that “we have always had absolute confidence in the integrity of the PLATO trial and we are proud of the important benefit Brilinta offers”. He added that “as one of AstraZeneca’s growth platforms, we are committed to delivering the full potential of this important medicine.”
Brilinta, sold as Brilique in the UK, has struggled to make much impact since launch, although second-quarter sales leapt 78% to $114 million and the DoJ decision should help. In the wake of Pfizer’s hostile takeover bid earlier this year, AstraZeneca set a sales target for Brilinta of $3.5 billion by 2023.
AstraZeneca recently announced the start of the SOCRATES trial, studying Brilinta for patients with acute ischemic stroke or transient ischemic attack, and the THEMIS study in patients with type 2 diabetes and coronary atherosclerosis. They form part of PARTHENON, the company’s largest ever clinical trial programme, involving more than 80,000 patients.
Meantime, AstraZeneca also announced positive top-line results from two Phase III studies investigating the antibiotic CAZ-AVI (ceftazidime-avibactam) as a treatment for hospitalised adults with complicated intra-abdominal infections (cIAI).
In the RECLAIM-1 and RECLAIM-2 Phase III studies, CAZ-AVI in combination with metronidazole showed statistical non-inferiority compared to meropenem. The primary endpoint was a clinical cure rate 28 to 35 days after randomisation.
AstraZeneca chief medical officer Briggs Morrison said the results “highlight the potential for CAZ-AVI to provide a much-needed new treatment option for serious and life-threatening intra-abdominal infections, especially where antibiotic resistance poses a threat to treatment”. CAZ-AVI, co-developed with Actavis, is also being evaluated in complicated urinary tract infections (cUTI), nosocomial pneumonia and for cIAI and cUTI ceftazidime-resistant infections.