Zealand Advances Danegaptide, Its Novel Drug Candidate, Into a Phase II Clinical Proof-of-Concept Study for Protection Against Reperfusion Injury in Patients With Myocardial Infarction

COPENHAGEN, Denmark, Nov. 20, 2013 (GLOBE NEWSWIRE) -- -- Company Announcement

No. 26/2013

  • Zealand-discovered peptide has the potential to be the first medicinal therapy to protect against tissue damage following reperfusion
  • The first patient has been treated in this Phase II study, conducted at Rigshospitalet in Denmark, a world leading Cardiac Center, and which is expected to enroll a total of 600 patients with myocardial infarction

Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL) ("Zealand") today announces that the first patient has been treated in a Phase II Clinical Proof-of-Concept study of danegaptide. Danegaptide is a novel Zealand invented dipeptide with potential as a first-in-class medicinal treatment to reduce tissue damage caused by reperfusion.

The objective of this Phase II study is to assess the efficacy and safety of danegaptide in reducing tissue damage from reperfusion injuries in patients with an acute myocardial infarction (ST-segment elevation myocardial infarction, STEMI) when added to standard treatment in the form of balloon dilatation (primary PCI). The study is a randomized, double-blind, placebo-controlled study, which will be conducted at Rigshospitalet in Copenhagen. It is expected to enroll a minimum of 600 STEMI patients, who will be randomized to treatment with either a high or a low dose of danegaptide or placebo in connection with a PCI procedure. Rigshospitalet treats more than 40% of Denmark's approximately 2,500 incidences of STEMI annually and is one of the world's leading and highly specialized Cardiac Centers.

The primary study endpoint is assessing the therapeutic effect of danegaptide in the reduction of tissue damage, measured as myocardial salvage index three months after the PCI procedure, by use of magnetic resonance imaging. The myocardial salvage index is a documented, strong prognostic marker for cardiac outcome (e.g. death and heart failure). Secondary study endpoints include clinical events of heart failure, re-hospitalizations for heart failure, pharmacodynamic effects and safety of danegaptide when added to the standard treatment of STEMI patients.

Commenting on the start of the danegaptide study, Dr. Thomas Engstrøm, PhD, DMSc, Lead Investigator and Chief Physician, the Heart Center, Rigshospitalet, Copenhagen University Hospital, said: "Over the past 15 years we have advanced the treatment of myocardial infarction substantially with the introduction of PCI, including mainly balloon dilatations, saving many patients' lives. At Rigshospitalet, we have pioneered balloon dilatations as first line treatment in this indication, and today such interventional procedures have become the established standard in most parts of the world. Despite having optimized also the logistics for bringing patients with an MI to the hospital as fast as possible, we still see severe cardiac tissue damage in many patients, which lead to reduced cardiac function and quality of life. The problems are to a large extent caused by reperfusion injuries following the therapeutic intervention, and danegaptide has demonstrated promising potential to help protect against this type of tissue damage. If successful, danegaptide could play a major role in enhancing the clinical outcome of percutaneous coronary intervention (PCI) after an acute MI and deliver important benefits to patients and society."

Commenting on the announcement, David Solomon, President and Chief Executive Officer of Zealand Pharma, said: "The commencement of this Phase II Clinical Proof-of-Concept study of danegaptide is a key event for Zealand in-line with our ambition to optimize and increase the value of our proprietary clinical pipeline of peptide candidates. Danegaptide has demonstrated great potential as a novel approach to help reduce cardiac tissue damage with additional potential in other forms of reperfusion injury, and we are excited about the unique opportunity of working with Rigshospitalet to further explore the therapeutic profile of this Zealand peptide.

"Rigshospitalet's Heart Center is renowned for its clinical expertise. We are proud to be working with this esteemed team which has conducted several other important studies that have helped to change the international guidelines for the treatment of patients with myocardial infarction."

Danegaptide has shown promising therapeutic properties in several relevant preclinical MI models assessing cardiac reperfusion injury. In a Phase I program, including 153 healthy subjects in three studies, danegaptide has been shown to be safe and well tolerated.

The danegaptide Phase II Clinical Proof-of-Concept study is expected to complete in the 2nd half of 2015.


For further information, please contact:

David H. Solomon, President and Chief Executive Officer

Tel: +45 2220 6300

Hanne Leth Hillman, Vice President and Head of IR & Corporate Communications

Tel: +45 5060 3689, email: hlh@zealandpharma.com

About danegaptide

Danegaptide (ZP1609) is a small dipeptide invented by Zealand, demonstrating both anti-arrhythmic and cytoprotective properties.

In a pre-clinical dog model of acute myocardial infarction (MI), i.e. an acute blood clot in the heart, danegaptide has demonstrated dose-dependent significant reductions in infarct size. In another relevant translational model of reperfusion injury associated with an acute MI, danegaptide significantly reduced infarct size compared to immediate full reperfusion1. Results from an extensive Phase I program with danegaptide, including three (3) individual studies in 153 subjects, showed that the compound was safe and well tolerated.


1 Journal of the American College of Cardiology: Volume 61, Issue 10, Supplement, Page E67, 12 March 2013

About Ischemic Reperfusion Injury

Ischemic heart disease is a disease characterized by reduced blood supply to the heart and it is one of the leading causes of death in the industrialized world. The condition is most often caused by a myocardial infarction (a heart attack), where a blood clot blocks blood flow for a longer period of time (ST segment elevation myocardial infarction, STEMI). In 2020, the incidence for STEMI is predicted to be 756.700 in US, EU and Japan combined. The treatment of acute myocardial infarction (AMI) is aimed at enabling the return of blood flow to the ischemic myocardium, thereby limiting the size of the infarct. Treatment options include fibrinolytic therapy, percutaneous coronary intervention (PCI) with thrombectomy, stent implantation and, and in some cases, coronary artery bypass grafting (CABG). Approximately 80% of STEMI patients undergo PCI procedure.

Although timely and effective reperfusion therapy of myocardium is the most effective method for reducing infarct size and improving the outcome in patients with STEMI, the process of myocardial reperfusion can paradoxically itself induce further cardiomyocyte death, a phenomenon known as myocardial reperfusion injury. Over the recent years many health care systems have been optimized to enable more timely and effective reperfusion and with advances in PCI technology and antiplatelet and antithrombotic agents for maintaining the patency of the infarct-related coronary artery. However, there are still no effective therapeutic compounds for preventing myocardial reperfusion injury. In this respect, myocardial reperfusion injury remains a neglected therapeutic target for cardioprotection in primary PCI patients and novel compounds in this field could leave patients with more viable cardiac tissue and reduced risk of developing heart failure.

Historically, investigations of treatments to decrease the ischemia reperfusion injury have often been based on preclinical studies in small animals with limited translational value to humans, and to date there are no marketed pharmacological treatments for the prevention of reperfusion injury. Both mechanical pre- and postconditioning (series of repetitive interruptions of the coronary blood flow during the PCI procedure) seem to protect cardiomyocytes during reperfusion. Reducing infarct size by 15% corresponds to a reduction in six month absolute mortality of 1% making this a meaningful marker for long term outcomes for patients.

About Zealand

Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL) ("Zealand") is a biotechnology company based in Copenhagen, Denmark. Zealand specializes in the discovery, optimization and development of novel peptide drugs and has a broad and mature pipeline of drug candidates identified through its own drug discovery activities. The company's focus lies in the field of cardio-metabolic diseases, diabetes and obesity in particular, and its lead drug invention is lixisenatide, a once-daily prandial GLP-1 agonist, which is licensed to Sanofi for the treatment of Type 2 diabetes. Lixisenatide (marketed by Sanofi as Lyxumia®) is approved in several countries, including Europe and Japan, and under regulatory review in a number of other countries globally. In the U.S., an NDA is planned to be submitted in 2015, after completion of the ELIXA Cardiovascular outcome study.

Zealand has a partnering strategy for the development and commercialization of its products and in addition to the license agreement with Sanofi in Type 2 diabetes, the company has partnerships with Boehringer Ingelheim in diabetes/obesity, Lilly in diabetes and obesity, Helsinn Healthcare in chemotherapy induced diarrhea and AbbVie in acute kidney injury.

For further information: www.zealandpharma.com l. @ZealandPharma


26-13_1120 - Danegaptide Phase II PoC study - UK_FINAL.pdf

Source:Zealand Pharma A/S