Armetheon, a specialty pharmaceutical company developing novel small molecule drugs for cardiovascular diseases, has reached agreement with the FDA for a single 1,000 patient final pivotal trial for its drug candidate, tecarfarin (Tecarfarin for AntiCoagulation Trial or TACT) prior to filing an NDA, which is currently projected to occur in 2019. 

Further, the agency indicated that Armetheon can amend the existing Special Protocol Assessment (SPA) for the 1,000 patient TACT study. Tecarfarin is positioned to potentially be, if approved, the oral anticoagulant (OAC) therapy of choice for patients who require anticoagulation with a Vitamin K antagonist (VKA), such as warfarin. This includes patients with prosthetic heart valves (PHV), repeat deep vein thrombosis or patients with chronic kidney disease (CKD) which complicates anticoagulant therapy. The pivotal trial will enroll patients with all indications for anticoagulation, thereby supporting a potential broad label if the product is approved.

Despite warfarin being the standard of care OAC for decades, physicians recognize its limitations related to its metabolism via cytochrome P450 (CYP). Patients who take a CYP interacting drug have variant CYP2C9 genetics or CKD have significant challenges to achieve stable anticoagulation control with warfarin. The TACT study will specifically enroll patients with these challenges to demonstrate tecarfarin's ability to provide improved anticoagulation control compared to warfarin. There are at least 15 conditions requiring OAC where a VKA such as warfarin is predominantly used, and these represent at least 1.7 million patients in the U.S. alone, with 91% of these patients taking at least one CYP interacting drug.

"To reach agreement with the FDA to conduct a 1,000 patient final phase III study prior to a potential NDA filing is unprecedented for an anti-thrombosis/cardiovascular drug," said Armetheon's President & Interim CEO, M. (Ken) Kengatharan, Ph.D. "This is because the primary endpoint for approval is an outcome measure called time in therapeutic range (TTR) of the international normalized ratio (or INR) which indicates how effective anticoagulation is managed in a particular patient."

In a prior interaction with Japan's Pharmaceuticals and Medical Device Agency (PMDA), Armetheon has received regulatory guidance for the development toward the Marketing Authorization Application for tecarfarin in Japan. The PMDA also accepted TTR as a primary end-point for approval.

Tecarfarin has been studied in close to 900 patients in 10 different clinical trials, including a prior pivotal trial and a study in CKD patients where tecarfarin was observed to have potential benefits based on pharmacokinetics when compared to warfarin.