Collaboration with Helsinn

Zealand has a partnership with Helsinn relating to elsiglutide, a potential first-ever treatment for the prevention of chemotherapy-induced diarrhea (CID).

The partnership relating to elsiglutide, a novel GLP-2 analogue invented by
Zealand, began in 2008. Global development and commercial rights in the field of
cancer-supportive care is licensed to Helsinn, which is developing elsiglutide as a
potential first-ever treatment to help prevent chemotherapy-induced diarrhea in
cancer patients.

Chemotherapy-induced diarrhea is a severe and potentially life-threatening
condition affecting cancer patients undergoing chemotherapy primarily with
regimens containing 5-fluorouracil (5-FU). 5-FU-based chemotherapy regimens
can result in up to 50-80% of cancer patients developing CID1. Currently, no
effective treatments are available for patients.

The condition is associated with dehydration, hospitalization, reduced quality of
lifeand suboptimal cancer treatment.

Large observational study in CID conducted by Helsinn

Helsinn has conducted a large international, multi-center, prospective, cohort observational study involving more than hundred sites in six European countries and in the US. The study objective is to gain a better understanding of the incidence rate and clinical impact of CID in colorectal and breast cancer patients. Together with the results from the Phase IIb trial, this study is important to guide the design of a potential pivotal Phase II program of elsiglutide. 
In June 2015, Helsinn completed enrollment of app. 1,700 cancer patients in the study. In May 2016, Helsinn announced the top-line results of the trial.


Elsiglutide

Elsiglutide (formerly referred to as ZP1846) is a novel GLP-2 peptide receptor agonist, invented by Zealand and licensed globally to Helsinn for its therapeutic use in Cancer Supportive Care. 
After evaluating the Phase IIb results, Helsinn has informed Zealand that in 2017 they will initiate one or more exploratory clinical trials in alternative patient settings with a higher incidence of CID, which, if successful, could lead to further development of elsiglutide.

Phase IIb results

The Phase IIb trial was a randomized, stratified, double-blind, double-dummy, parallel group, placebo-controlled, dose finding, multicenter, multinational, Phase IIb trial in patient with colorectal cancer receiving 5-fluorouracil (5-FU)-based chemotherapy (FOLFOX or FOLFIRI). Patients received, starting from the day of chemotherapy administration, a single daily dose subcutaneously of elsiglutide 10, 20 or 40 mg or placebo for four consecutive days. Each patient was in the study for three consecutive chemotherapy cycles. The treatment period for each patient was four consecutive days of the first two chemotherapy cycles.

Two populations were planned for this study. The population receiving FOLFOX or FOLFIRI without monoclonal antibody was defined as the Target population (at least 120 patients per treatment group, for a total 480 patients), while the population concomitantly receiving monoclonal antibody was defined as the Additional population (up to 30 patients per treatment group, total maximum of 120 patients). The primary endpoint was the proportion of patients with diarrhea of grade > 2 or more during the first cycle of chemotherapy. The primary analysis took into consideration only the target population.

In May 2016, Helsinn reported top-line results from its clinical Phase IIb dose-finding trial to assess the efficacy of elsiglutide in the prevention of diarrhea induced by chemotherapy in patients with colorectal cancer. The results showed a positive numerical but not statistically significant effect of elsiglutide on the primary endpoint, defined as the proportion of patients experiencing a maximum grade ≥ 2 diarrhea during the first cycle of chemotherapy. In the trial, elsiglutide demonstrated a favorable safety and tolerability profile.

Terms of license agreement with Helsinn

Under the agreement, Helsinn is responsible for the conduct and the financing of all clinical development and commercialization of elsiglutide, and Zealand is eligible to receive milestone payments and royalties on sales. For further information, see Helsinn Healthcare.