AstraZeneca (AZ) has announced that it will stop its post-marketing study of bleeding reversal agent Andexxa (andexanet alfa) after the trial met its primary endpoint earlier than planned.
The phase 4 ANNEXA-I study has been assessing the safety and efficacy of the drug versus standard care in more than 450 patients experiencing an intracranial haemorrhage who have received oral Factor Xa-inhibitor treatment, including apixaban and rivaroxaban.
Results from a planned interim analysis of the trial showed that Andexxa-treated patients experienced superior haemostatic efficacy – the ability to limit the expansion of a potentially life-threatening bleed in the brain – compared with the control arm, leading the data monitoring board to recommend that the study be ended.
Millions of people worldwide depend on Factor Xa inhibitors to manage their risk of blood clots developing, but these medicines carry a small but significant risk of an acute major bleed.
AZ reports that there is an ‘urgent need’ for access to specific reversal agents for patients treated with Factor Xa inhibitors as major bleeding, including intracranial haemorrhage, can be life threatening and can happen inside the body, so may not be visible.
Andexxa, which is specifically designed to rapidly reverse the anticoagulation effects of direct oral Factor Xa inhibitors, has already been granted accelerated approval in the US and is conditionally approved in the EU, UK and Switzerland as Ondexxya for adults treated with Factor Xa inhibitors apixaban and rivaroxaban.
The company said it will now initiate closure of ANNEXA-I and proceed with regulatory filings in the US and EU to convert to full label approval.
Mene Pangalos, executive vice president, BioPharmaceuticals R&D, AZ, said: “We are proud to offer the first and only approved treatment to specifically reverse Factor Xa inhibitor activity and help achieve haemostasis, providing an effective and reliable treatment when immediate care is required.”
Tom Keith-Roach, president, AZ UK, said: “The growing adoption of Factor Xa inhibitors has led to a corresponding need to urgently address Factor Xa inhibitor-related intracranial haemorrhage. [The] announcement demonstrates the potential of andexanet alfa for patient care and emergency medicine in the UK.
“We look forward to engaging with the National Institute for Health and Care Excellence to ensure there is equitable access to andexanet alfa for patients who are on Factor Xa inhibitors across the UK to manage this significant unmet need in situations of life-threatening or uncontrolled bleeding.”
The announcement comes just days after AZ shared positive results from a late-stage study evaluating Tagrisso (osimertinib) as an additional treatment for certain lung cancer patients.
The results, which were presented at the American Society of Clinical Oncology annual meeting, showed that the drug reduced the risk of death by 51% compared to placebo in patients with early-stage epidermal growth factor receptor-mutated non-small cell lung cancer who had undergone surgery to remove their primary tumour.