- Pivotal Phase 3 trial for tecarfarin under FDA-approved Special Protocol Assessment provides clear regulatory pathway to the $8.5 billion U.S. oral anticoagulant market -
JACKSONVILLE, Fla. and IRVINE, Calif., Dec. 12, 2017 (GLOBE NEWSWIRE) -- Espero BioPharma, a biopharmaceutical company focusing on the late-stage development and commercialization of drugs to treat cardiovascular diseases, today announced a strategic update on its clinical and regulatory strategies for tecarfarin, an oral anticoagulant (OAC). Tecarfarin and budiodarone were added to Espero’s product pipeline through the company’s merger with Armetheon, Inc. earlier this year. The Tecarfarin for Anticoagulation Trial (TACT) is expected to initiate in the second quarter of 2018, with interim data anticipated in the fourth quarter of 2018 and filing of a New Drug Application with the U.S. Food and Drug Administration (FDA) planned for 2020. The Company also plans to initiate a second Phase 2 clinical program for budiodarone, a potential best-in-class anti-arrhythmic agent for the treatment of refractory atrial fibrillation (AF).
“With the initiation of TACT, which is the last remaining pivotal study for tecarfarin, and the Phase 2 clinical program for budiodarone planned for 2018, we are well positioned to achieve a number of transformative clinical and regulatory milestones in the year ahead,” said Quang Pham, Chairman and Chief Executive Officer of Espero. “Tecarfarin and budiodarone each have the potential to become best-in-class agents, creating significant value for patients, physicians and our investors. We look forward to working with our clinical investigators and the FDA to advance these promising product candidates through the clinic and to patients who are underserved by available anticoagulant and anti-arrhythmic agents.”
Espero BioPharma also announced that two renowned cardiovascular specialists are leading the Phase 3 trial for tecarfarin: Christopher Granger, MD, Professor of Medicine at Duke University and Director of Duke Health’s Cardiac Intensive Care Unit and Richard Whitlock, MD, Principal Investigator, The Perioperative and Surgery Program at the Population Health Research Institute at McMaster University. The company will also expand its clinical operations team and infrastructure.
The Tecarfarin Difference
Tecarfarin has the potential to be the OAC therapy of choice for patients who require anticoagulation with a Vitamin K antagonist (VKA), such as warfarin, including patients with prosthetic heart valves (PHV), AF and valvular pathology, recurrent deep vein thrombosis or patients with chronic kidney disease (CKD), which complicates anticoagulant therapy. Warfarin has been the standard of care OAC for more than six decades. Despite the approval of five non-Vitamin K OACs (NOACs) since 2010, warfarin remains the most widely used OAC in the United States even though it is prone to markedly unstable anticoagulation in a significant numbers of patients due to CKD, drug-drug interactions with medications metabolized through the cytochrome P450 (CYP) pathway and genetic variations in CYP2C9. Because of these very common factors, warfarin is the most commonly implicated drug for adverse drug reactions and hospitalizations in the United States, primarily from bleeding events. The five NOACs are either not approved or are contraindicated in 15 distinct indications that comprise a subpopulation of 1.5 million patients in the U.S. Tecarfarin is metabolized independent of the CYP450 pathway and its metabolism and elimination are unaffected by CYP450 inhibition resulting from genetic variation, renal failure or drug-drug interactions.
“Despite known potential complications associated with vitamin K antagonists like warfarin and the availability of NOACs, warfarin still accounts for 56 percent of U.S. OAC prescriptions as of March 2017, according to IMS. An improved vitamin K antagonist for a broad array of clinical indications and patient populations would be an important new tool for oral anticoagulation,” said Christopher Granger, MD, Co-Principal Investigator of TACT.
“Data from 900 patients treated with tecarfarin in clinical trials to date suggest that this new OAC has an acceptable safety profile and has the potential to most benefit patients for whom stable anticoagulation is difficult to achieve and have the highest unmet need. If TACT is successful, tecarfarin could be a game changer in managing patients who require anticoagulation therapy,” said Richard Whitlock, MD, Co-Principal Investigator of TACT.
Accelerated Regulatory Pathway for Tecarfarin
Under the Special Protocol Assessment (SPA) approved by the FDA, TACT is designed as an open-label study that will evaluate time-in-therapeutic range (TTR) as the primary endpoint for approval in 1,000 patients randomized to receive tecarfarin or warfarin. The study population is enriched for patients in whom stable anticoagulation is difficult to achieve with warfarin and thus have greatest unmet medical need. TTR is the percentage of time that the patient’s international normalized ratio (INR), a measure of how long it takes for blood to clot, is within the target therapeutic range for the desired blood clotting that is necessary to prevent thromboembolic events. Improved TTR yields improved clinical outcomes and is accepted by the FDA, PMDA, EMA and the medical community as a validated measure of OAC safety and efficacy. Each 1% improvement in TTR is associated with a 1-3% decrease in the rate of mortality or stroke and thus is a validated independent outcomes measure. No clinical outcome study will be required for approval of tecarfarin. In addition to being subject of a SPA, regulators in the European Union (EU) and Japan have also accepted the TACT study design and TTR as the primary endpoint for approval.
“The TACT SPA provides Espero with a clear, accelerated regulatory pathway for tecarfarin,” added Mr. Pham. “Our ability to conduct TACT in 1,000 patients using TTR as an endpoint dramatically reduces the time, cost and overall risk required to advance this promising OAC toward approval in multiple markets and offers multiple near-term opportunities for value creation.”
Budiodarone Clinical Trial in AF
Espero also expects to initiate its third Phase 2 clinical trial of budiodarone in the second half of 2018. Budiodarone is being evaluated as an anti-arrhythmic agent for the treatment of refractory AF. In clinical trials to date, budiodarone has demonstrated superior safety and efficacy profiles compared with amiodarone and dronedarone, which are approved anti-arrhythmic agents. Unlike these other agents, budiodarone has a rapid clearance and short half-life, predictable dose response and does not accumulate in tissues, eliminating the lung and liver toxicity that has been observed with amiodarone and dronedarone. Amiodarone, which is standard of care in AF, is associated with unpredictable dose responses and medium- and long-term toxicity. As such, Espero believes that budiodarone has the potential to become a best-in-class anti-arrhythmic agent. First-line therapies for AF fail in up to 40-60% of patients and it is estimated that 2-3 million U.S. patients are living with refractory AF. Espero anticipates that preliminary Phase 2 data are expected to be available in the first half of 2019.
About Espero BioPharma, Inc.
Espero BioPharma, Inc. is a biopharmaceutical company focusing on the late-stage development and commercialization of drugs to treat cardiovascular diseases. Through Espero Pharmaceuticals and Jacksonville Pharmaceuticals, its wholly owned subsidiaries, the company markets and distributes selected standard of care cardiovascular pharmaceutical products including GoNitroTM (nitroglycerin) sublingual powder and Nitrolingual® Pumpspray (nitroglycerin lingual spray) and its authorized generic. The Company has offices located in Jacksonville, FL and Irvine, CA. Additional information about Espero BioPharma is available at http://esperobio.com.
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