Astellas Pharma has suffered a setback after a mid-stage study of its new anticoagulant darexaban showed that the new oral Factor Xa inhibitor increased bleeding two- to four-fold in patients with acute coronary syndrome.
The Phase II, 1,279-patient-study presented at the European Society of Cardiology meeting in Paris saw participants receive one of six darexaban regimens: 5mg twice-daily (bid), 10mg once-daily (AD), 15mg bid, 30mg qd, 30mg bid or 60mg qd, or placebo, in addition to dual antiplatelet treatment (aspirin and clopidogrel) for 24 weeks.
The primary outcome of the study (major or clinically relevant non-major bleeding events) was numerically higher in all darexaban arms than in the placebo group. Furthermore, there was no decrease in rates of efficacy outcome (a composite of death, stroke, myocardial infarction, systemic thromboembolic events and severe recurrent ischaemia) with darexaban versus placebo. However, researchers noted that the study was underpowered to evaluate efficacy and there were no other significant drug-related safety concerns associated with darexaban.
Gabriel Steg of the Bichat Hospital in Paris, who presented results from the RUBY-1 trial at the ESC Congress, said the study produced no other safety concerns but "establishing the role of low-dose darexaban in preventing major cardiac events after ACS now requires a large Phase III trial".
Darexaban belongs to the same class as Bristol-Myers Squibb and Pfizer's Eliquis (apixaban), which has demonstrated impressive results for stroke prevention in atrial fibrillation patients but also failed in patients with ACS, again due to excessive bleeding.
In February, Astellas withdrew a market authorisation application for darexaban in Japan for the prevention of venous thromboembolism in patients at risk, such as those undertaking orthopaedic surgical procedures in the lower limbs.
New bladder drug filed in USA, Europe
Meantime, Astellas announced that it has filed mirabegron in Europe and the USA for urgency, urinary frequency and urge urinary incontinence associated with overactive bladder.
Approved in Japan last month, as Betanis, mirabegron is a first-in-class beta-3 adrenoceptor agonist and the once-daily tablet facilitates bladder filling and storage of urine. Astellas already markets an OAB treatment, Vesicare (solifenacin).
Astellas also noted that it will book an extraordinary profit of 10.07 billion yen (about $131.3 million) through the sale of a research centre site in Tokyo.The sale, to Sumitomo Realty & Development Co, was prompted by a desire "to improve asset efficiency through reduction and liquidation of assets".