Astellas pulls Japanese filing for darexaban
This article was originally published in Scrip
Astellas has withdrawn a Japanese approval filing for its oral direct Factor Xa inhibitor darexaban maleate (YM150), citing a request from regulators for additional clinical studies.
The future plan for and timing of a possible resubmission are as yet unclear, the company saying that it would await the outcome of partnering discussions for the product in other major markets before settling on its Japan strategy.
The decision to pull the application - made last September for the initial indication of prevention of venous thromboembolism (VTE) in at-risk patients (such as those undergoing lower limb orthopaedic surgery) - was taken following discussions with Japan's PMDA. The regulator said that supplemental studies would be needed to secure an approval, Astellas noted.
The submission was supported by data from two Phase II/III Asian studies in patients undergoing elective total knee or hip replacement surgery, which the company has said showed benefits over placebo in terms of prevention of VTE conditions.
These include both pulmonary embolism and deep vein thrombosis (DVT), the latter being a common result of lower limb and abdominal orthopaedic surgery that can lead to the formation of the blood clots that cause pulmonary embolism.
The decision is a setback for what is one of the company's main near-term product hopes, and looks likely to delay any Japanese approval of darexaban for this use by up to several years. But the product so far remains on track for what will be its main commercial indication of the prophylaxis of thromboembolic complications associated with atrial fibrillation (AF), for which Phase IIb studies in Europe and Japan/Asia have been completed.
Astellas is currently seeking global licensees for this setting and also in the US and Europe for the orthopaedic VTE prevention indication. Phase IIb/III trials in the US and Europe for this use have been completed, and a Phase IIb European trial for the prevention of ischaemic vascular events in patients with recent acute coronary syndromes should be completed in the first half of this year.
The delay will also give time for other competing novel anticoagulants to gain ground, at least in the orthopaedic setting. Foremost among these is Daiichi Sankyo's oral Factor Xa inhibitor edoxaban, which was filed in Japan ahead of darexaban in April 2010 for the prevention of VTE after major orthopaedic surgery.
GlaxoSmithKline's same-class product Arixtra (fondaparinux) is already approved in Japan for the treatment of acute pulmonary thromboembolism and acute DVT, as well as for VTE in high-risk orthopaedic and abdominal surgery patients.
Boehringer Ingelheim's oral direct thrombin inhibitor Prazaxa (dabigatran) recently became the first in the new wave of anticoagulants to be approved for the AF indication in Japan, specifically for the prevention of ischaemic stroke and systemic embolism in patients with non-valvular AF.