Other mid-term value driversDanegaptide and elsiglutide

Danegaptide is a proprietary Zealand asset with the potential to become the first medical treatment for ischemic reperfusion injuries – An area of large unmet medical need. Ongoing Phase II Proof-of-Concept study to read out in the 2nd half of 2015. 

Elsiglutide, in partnership with Helsinn, has shown favourable clinical Phase IIa results and the next step in development is a Phase IIb dose-finding study, planned to start in the 2nd half 2014.

Danegaptide – A potential first-in-class medicinal treatment for ischemic reperfusion injuries

Danegaptide is a small dipeptide invented by Zealand, which has demonstrated both anti-arrhythmic and cytoprotective (cell-preserving) properties. 

Danegaptide – a novel, small peptide therapeutic invented by Zealand

In a pre-clinical model of reperfusion injuries related to acute myocardial infarction (AMI), i.e. an acute blood clot in the heart, danegaptide has demonstrated dose-dependant significant reductions in infarct size. The safety of danegaptide has been evaluated in an extensive Phase I program, including three individual studies in 153 subjects. Results showed that the compound was safe and well tolerated.

In November 2013, we advanced danegaptide in development with the initiation of a Phase II Clinical Proof-of-Concept study. The study objective 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 up to 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. 

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.

The Phase II study is expectedto complete in the 2nd half of 2015. Results will be decisive to define the future value of danegaptide

The Phase II Proof-of-Concept study is expected to complete in the 2nd half of 2015. Study results will be decisive in demonstrating danegaptide’s effect in the protection of cardiac tissue against ischemic reperfusion injuries, an area of large unmet medical needs. In addition, the outcome of this study will help define danegaptide’s futher potential as a possible general therapy for the prevention of reperfusion injuries, e.g. injuries caused by reperfusion in connection with organ transplantation, kidney injuries and stroke.

Interview with Dr. Thomas Engstrøm: 
Ischemic reperfusion injury represent a serious therapeutic challenge

 

Q

You and the team at Rigshospitalet have extensive experience in the treatment of patients with cardiac disease, including acute myocardial infarction (AMI) – How would you describe treatment outcomes today? 

A

 

Over the past few decades, we have seen significant advances in the treatment of patients with an AMI, i.e. a blood clot in the heart, which has brought the patient survival rate up to
90% from previously around 40%. This has been achieved to a large extent via interventional procedures, referred to as percutaneous coronary intervention (PCI), where a balloon catheter inserted into the clotted vessel to open for blood flow (reperfusion). In most developed parts of the world, PCI has become the standard treatment of AMI, and in some countries, including Denmark, the time to treatment has also been reduced to a minimum via optimal logistics and hospital set-ups, important to salvage more cardiac tissue. 

Despite the advances in the treatment of AMI, we are left with a serious therapeutic challenge: while reperfusion of the ischemic myocardial tissue via timely PCI procedures is key to saving patient lives, the return of blood flow in itself causes additional injuries to the heart. Such injuries, which are generally referred to as myocardial reperfusion injuries result in decreased cardiac function and quality of life for patients treated for AMI including an elevated risk of heart failure.

Q

What options do we have today to prevent or treat myocardial reperfusion injuries? 

A

Our team at Rigshospitalet has played an active role over the last many years in finding treatment options to reduce reperfusion injuries. So far, we have found a few therapeutic procedures which may bring some benefit to patients, but we do not yet have any established treatment available to significantly prevent or treat cardiac reperfusion injuries. 

Thus we still see a large unmet need for novel preventive therapies, which can help improve the overall clinical outcome and quality of life for patients presenting with an AMI.

Q

How do you see the route forward in terms of treatment opportunities for ischemic reperfusion injuries and improved prospects for patients? 

A

Finding a way to effectively prevent or reduce reperfusion injuries would be an important advance in the treatment of AMI. It would ensure a better overall treatment outcome with reduced risk of another cardiac event, significantly improving quality of live for patients. This would be beneficial also from a Health Economic point of view. Danegaptide, which we are currently evaluating in a Phase II Proof-of-Concept study in collaboration with Zealand, represents a relevant medicinal approach. In the study, we are exploring if treatment with this peptide molecule in addition to PCI may reduce reperfusion injuries and meet our needs.

Elsiglutide – For the prevention of chemotherapy induced diarrhea, an area of large unmet medical needs

Elsiglutide is a novel, potent and selective GLP-2 peptide agonist invented by Zealand

Elsiglutide is a GLP-2 receptor agonist, invented by Zealand. Designed for once-daily subcutaneous or intravenous administration, this peptide drug candidate has shown the ability to normalize gastrointestinal function via stimulation of the small intestinal mucosa.
 
Global development and commercial rights to elsiglutide in the field of cancer supportive care are licensed to Helsinn Healthcare, which is developing this therapeutic for the prevention of chemotherapy induced diarrhea (CID). Helsinn is a private pharmaceutical company based in Switzerland with a worldwide leading position in cancer supportive care.

Initiation of phase IIb study in H2 2014

Helsinn has completed a randomized, double-blind, placebo-controlled Phase IIa Proof-of-Concept study with elsiglutide in 138 patients with colorectal cancer receiving chemotherapy. Based on the favourable results from the Phase IIa study, Helsinn made a decision in 2013 to advance clinical development of elsiglutide and is preparing for the initiation of a Phase IIb dose-finding study in the 2nd half 2014. 

As part of the elsiglutide development program, Helsinn has undertaken a large international, multicenter, prospective, cohort observational study in US and EU to assess the incidence of chemotherapy-induced diarrhea in colorectal and breast cancer patients. 

Results from the study together with the outcomes on the planned Phase IIb study will be important to optimally design the full clinical Phase III development program for elsiglutide.