URGENT Study Provides Important New Insight into the Use of Dyspnea as a Clinical Endpoint for Evaluating New Treatments for Acute Heart Failure Syndromes

Business Wire,  July 16, 2008  

• E-mail
• Print
• Link

Study Better Positions EKR to Advance the Development of Ularitide for AHFS

BEDMINSTER, N.J. -- EKR Therapeutics, Inc., a specialty pharmaceutical company focused on providing novel products for the acute-care hospital setting, today said that its prospective, observational study of heart failure patients showed that early evaluation of dyspnea (shortness of breath) is crucial in assessing patients with acute heart failure syndromes (AHFS).

Prior to the study, referred to as URGENT (Ularitide Global Evaluation in Acute Decompensated Heart Failure), there had been a scarcity of prospective data regarding the severity of dyspnea and its resolution in AHFS patients treated with conventional therapies in the hospital emergency department (ED) and other acute-care settings.

AHFS accounts for over one million hospitalizations in the US annually. Dyspnea is a presenting symptom in approximately 80-90% of admissions and requires urgent intervention. It is usually treated with diuretics and vasodilators. However, these interventions may be associated with adverse effects on cardiac and renal functions. The safety and efficacy of these agents have not been well studied. There is a need for developing a new agent that can improve symptoms without negatively affecting cardiac or renal function.

Most, if not all, studies conducted to date enrolled patients within 24-48 hours after presentation, when dyspnea was less likely to be present or severe. In addition, there was no standardization of dyspnea measurement. URGENT-Dyspnea, an international, multi-centered study, evaluated dyspnea in more than 500 patients with confirmed AHFS. A principal study objective was to determine the effect of early administration of standard therapies on dyspnea as a clinical endpoint. The effects on dyspnea of conventional heart failure drugs given in the acute setting were measured within one hour of the physician's first contact with the patient (baseline), and changes were assessed over the subsequent 6 hours of treatment.

The data, as recently reported at the 2008 Heart Failure Congress in Milan by the Director of the study, Peter S. Pang, MD, Associate Medical Director, Department of Emergency Medicine of the Feinberg School of Medicine, Northwestern University, demonstrated that conventional heart failure medications administered in the acute setting resulted in a large decrease in the overall severity of dyspnea compared with baseline. Consequently, the findings of the URGENT-Dyspnea study have significant potential implications for clinicians and regulatory authorities with regard to targeting AHFS treatments and designing protocols for clinical trials of new drug therapies.

To date, clinical trials of new AHFS drugs have generally focused on measuring dyspnea relatively late; 24 to 48 hours after patients enter the acute setting and receive standard treatment which, according to the URGENT-Dyspnea study, can improve dyspnea substantially. Thus, the design of clinical trials which target dyspnea as a primary endpoint may need to consider earlier enrollment, particularly with regard to US and EU regulatory guidelines that pivotal trials of new AHFS drugs demonstrate symptomatic improvement over standard therapy.

"The URGENT-Dyspnea data suggest that not only when, but also how dyspnea is measured is critical," said Graham May, M.D., EKR's Chief Medical Officer. "This is valuable information for those designing new studies of heart failure drugs and will greatly help EKR in planning definitive trials of ularitide."

"We now know dyspnea improves early," stated Mihai Gheorghiade, M.D., Professor of Medicine and Surgery at Northwestern University Feinberg School of Medicine and Co-Chair with Professor Alexadre Mebazaa of the URGENT-Dyspnea study. Dr. Gheorghiade further stated "Novel therapies, in addition to dyspnea relief, need to focus on protecting or improving both cardiac and renal function, as these contribute substantially to the high post-discharge morbidity and mortality of AHFS."

Ularitide is a synthetic form of urodilatin, a naturally occurring human natriuretic peptide that is involved in regulating blood pressure and the excretion of water and sodium from the kidneys. EKR obtained worldwide rights, including all intellectual properties, to ularitide in March 2008 as part of the Company's purchase of a portfolio of acute-care cardiovascular products from PDL BioPharma, Inc. (NASDAQ: PDLI).

The ularitide development programs have completed Phase I and Phase II studies, respectively, in the US and Europe. Initial results show hemodynamic and symptomatic improvements. Importantly, they also suggest renal improvement, which requires further clinical investigation.

EKR, which has dramatically expanded its strengths in the US acute-care market from one product and 10 sales representatives in late 2006 to four products and nearly 100 sales people by early 2008, said it is exploring strategic alliances for ularitide worldwide.