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Acute Pulmonary Embolism Trial Confirms Safety and Efficacy of Ultrasound Accelerated Endovascular Thrombolysis

T.BTO

EKOS Corporation, a BTG International group company (BTG plc (LSE: BTG)), notes the presentation of the results of the SEATTLE II trial this afternoon at ACC.14, the 63rd Annual Scientific Session and Exposition of the American College of Cardiology in Washington, DC in the United States. The results were presented by Dr. Gregory Piazza, MD, Staff Physician, Cardiovascular Division, Brigham and Women’s Hospital and Instructor of Medicine, Harvard Medical School.

The SEATTLE II study is a prospective, single-arm, multi-center trial to evaluate the safety and efficacy of ultrasound-facilitated catheter-directed low-dose thrombolysis, using the EKOS EkoSonic® Endovascular System, for treating 150 patients with acute massive (N=31) or submassive (N=119) pulmonary embolism (PE). Chest computed tomography had to demonstrate proximal PE and a dilated right ventricle (RV/LV ratio ≥ 0.9) for patients to be eligible to participate. A dose of 24 mg tPA (thrombolytic) was used in the trial, administered either as 1 mg/hour for 24 hours with a unilateral catheter or 1 mg/hour/catheter for 12 hours with bilateral catheters. The mean RV/LV ratio in the study decreased from 1.55 pre-procedure to 1.13 at 48 hours post-procedure, a difference of 0.42 (p<0.0001).

Massive PE has a mortality rate of about 52% at 90 days.1 In the SEATTLE II study, there were 31 patients presenting with massive PE manifested by syncope and hypotension. However, no patients with massive PE died within the 30 day follow up period. Of 150 patients in the overall study, only one death was directly attributed to PE.

There were no intracranial hemorrhages and no fatal bleeding events. Major bleeds occurred in 17 patients and was comprised of one severe bleed and 16 moderate bleeds. Six of the major bleeds occurred in patients with co-morbidities known to be associated with an increased risk of bleeding during thrombolytic therapy.

The abstract concluded that ultrasound-facilitated catheter-directed low-dose fibrinolysis for acute PE minimizes the risk of intracranial hemorrhage, improves RV function, and decreases pulmonary hypertension.

Samuel Z. Goldhaber, MD, Professor of Medicine, Harvard Medical School and Director, Thrombosis Research Group, Brigham and Woman’s Hospital (Boston, MA), and Principal Investigator for SEATTLE II said, “This trial represents a breakthrough in demonstrating the safety and efficacy of thrombolytic therapy for acute PE. The reduction of the RV/LV ratio by 0.42 is substantial and clinically significant, without any intracranial hemorrhage and using a much reduced lytic dose. These findings establish a new rationale for considering thrombolysis in both massive and submassive PE.”

Dr. Stavros Konstantinides, MD, Professor for Clinical Trials and Deputy Scientific Director, Center for Thrombosis and Hemostasis, Johannes Gutenberg University of Mainz, Germany, and principal investigator of PEITHO trial explains, “Aside from the massive PE patients who are in need of emergent therapy, the submassive PE patients while hemodynamically stable exhibit an elevated risk of clinical deterioration if managed conservatively, as observed in the PEITHO trial. The SEATTLE II study presents promising data in support of a catheter-based modality to provide rapid unloading of the right heart, thus reducing the risk of further deterioration.”

Matt Stupfel, General Manager at EKOS Corporation, added, “The recently published ULTIMA trial results demonstrated that EKOS treatment was clinically superior to anticoagulation with heparin alone in reversing right ventricular dilation at 24 hours, without an increase in bleeding complications. Together, the SEATTLE II and ULTIMA trial results provide compelling evidence that treatment with the EkoSonic® Endovascular System improves the standard of care for patients with acute pulmonary embolism.”

About BTG

BTG is a growing international specialist healthcare company that is developing and commercialising products targeting acute care, cancer and vascular diseases. The company has diversified revenues from sales of its own marketed products and from royalties on partnered products, and is seeking to acquire new programs and products to develop and market to specialist physicians. To find out more about the BTG International group companies and our products, visit www.btgplc.com.

About EKOS Corporation and the EkoSonic® Endovascular System

EKOS Corporation, a BTG International group company, pioneered the development and clinical application of ultrasound infusion technologies in medicine, introducing its first system for the treatment of vascular thrombosis in 2005. Today, interventional radiologists, cardiologists, cardiothoracic and vascular surgeons at leading institutions around the world use the EKOS EkoSonic® Endovascular System to provide faster, safer and more complete dissolution of thrombus. To find out more about the EKOS EkoSonic® Endovascular System, visit www.ekoscorp.com.

EKOS, EkoSonic, MicroSonic are the trademarks of EKOS Corporation, a BTG International group company. BTG and the BTG roundel are registered trademarks of BTG International Ltd in US, EU and certain other territories and trademarks of BTG International Ltd elsewhere.

Statements of indications:

USA FDA Cleared Indications:

The EkoSonic® Endovascular Device is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature. The EkoSonic® System is cleared for the infusion of solutions into the pulmonary arteries.

Contraindications:

Not designed for peripheral vasculature dilation purposes. The system is contraindicated when, in the medical judgement of the physician, such procedure may compromise the patient’s condition. See device instructions for use for complete prescribing information.

The CE Mark (CE0086) has been affixed to the EkoSonic® and MicroSonicTM products with the following indications for use:

Peripheral Vasculature

The EkoSonic® Endovascular Device, consisting of the Intelligent Drug Delivery Catheter (IDDC) and the MicroSonicTM Device (MSD), is intended for controlled and selective infusion of physician-specified fluids, including thrombolytics, into the peripheral vasculature. All therapeutic agents utilized with the EkoSonic® Endovascular System should be fully prepared and used according to the instruction for use of the specific therapeutic agent.

The MicroSonicTM SV Endovascular Device is intended for the controlled and selective infusion of physician specified fluids, including thrombolytics, into the peripheral vasculature.

Pulmonary Embolism

The EKOS EkoSonic® Endovascular System is intended for the treatment of pulmonary embolism patients with ≥ 50% clot burden in one or both main pulmonary arteries or lobar pulmonary arteries, and evidence of right heart dysfunction based on right heart pressures (mean pulmonary artery pressure ≥ 25mmHg) or echocardiographic evaluation.

Notes to Editors

Submassive Pulmonary Embolism (PE) definition – patients with pulmonary embolism that have normal systemic blood pressure and confirmed heart dysfunction.

Massive Pulmonary Embolism (PE) definition – patients with pulmonary embolism that have systemic hypotension (systemic blood pressure that is <90 mmHg) and confirmed heart dysfunction.

rt-PA – recombinant tissue plasminogen activator – a recombinant protein involved in the breakdown of blood clots.

RV/LV ratio is the extent to which right ventricle is dilated in relation to the left ventricle. Also known as an indicator for the right heart dysfunction.

PE occurs in approximately 1 million patients in Europe annually and 600,000 in the US, causing or contributing to 200,000 deaths each year. (According to http://www.sirweb.org/patients/deep-vein-thrombosis/ and company internal data.)

Pulmonary hypertension (PH) is increased pressure in the pulmonary arteries. These arteries carry blood from heart to lungs to pick up oxygen. It causes symptoms such as shortness of breath during routine activity, tiredness, chest pain, and a racing heartbeat.

PEITHO trial - this trial confirmed the benefit of thrombolytic therapy among submassive PE patients, but also demonstrated that systemic IV infusion of thrombolytic drugs carries significant bleeding risk.

Syncope – transient loss of consciousness.

References:

1. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER), Goldhaber et al. Lancet. 1999 Apr 24;353(9162):1386-9.

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