Date: 2016-05-04
Type of information: Results
phase: 2b
Announcement: results
Company: Zealand Pharma (Denmark) Helsinn (Switzerland)
Product: elsiglutide (ZP1846)
Action
mechanism: Glucagon-like Peptide (GLP) analogue. Elsiglutide is a novel GLP-2 peptide receptor agonist, invented by Zealand and licensed globally to Helsinn for its therapeutic use in Cancer Supportive Care.
Disease: prevention of chemotherapy-induced diarrhea in cancer patients
Therapeutic area: Cancer - Oncology
Country: Belarus, Bulgaria,Czech Republic, Germany, Hungary, Poland ,Russia, Ukraine
Trial
details: The Phase IIB trial with elsiglutide is a randomized, double-blind, parallel group, placebo-controlled, dose finding study, which is planned to enroll up to 600 colorectal cancer patients receiving 5-FU-based chemotherapy regimens (FOLFOX or FOLFIRI). The trial includes a subgroup of 120 patients who will be treated also with an approved monoclonal antibody. The study objective is to assess the efficacy of three different doses of subcutaneous elsiglutide versus placebo in the prevention of CID. The primary endpoint is the proportion of patients experiencing diarrhea of grade 2 or more during the first cycle of 5-FU based chemotherapy. The results of the Phase IIB trial are expected to be available in the first half of 2016 The Phase IIa study is a randomized, double-blind and placebo-controlled proof-of-concept study to assess the efficacy and safety of elsiglutide for the prevention of chemotherapy-induced diarrhea (CID) in colorectal cancer patients receiving 5-fluorouracil (5-FU)-based chemotherapy. In the study, elsiglutide is administered subcutaneously in parallel with 5-FU. The Phase IIa study is conducted by Helsinn and plans to enroll 138 cancer patients in approximately 20 centers across European countries. (NCT01543451)
Latest
news: * On May 4, 2016, Zealand announced that Helsinn has 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. Results from a previous clinical Phase IIa trial conducted by Helsinn have shown that elsiglutide reduces the severity of chemotherapy-induced diarrhea (CID) in colorectal cancer patients with a good safety profile. * On May 28, 2013, Zealand and Helsinn have jointly announced that Helsinn has concluded a Phase IIa study with elsiglutide for the prevention of chemotherapy-induced diarrhea in cancer patients, with positive results. In a randomized, double-blind, placebo-controlled Proof-of-Concept Phase IIa clinical study, Helsinn has assessed the efficacy and safety of elsiglutide for the prevention of chemotherapy-induced diarrhea. The study was conducted under an open Initial New Drug (IND) application with the FDA in 19 European centers and enrolled 138 colorectal cancer patients. Concurrently, Helsinn has completed a Phase Ib study, showing that elsiglutide is safe and tolerated at doses well above expectable therapeutic level. Based on the results from the proof-of-concept study, Helsinn is now planning a Phase IIb study to further evaluate the efficacy of elsiglutide as a novel therapy to prevent chemotherapy induced diarrhea in cancer patients. * On March 2, 2012, Zealand Pharma and Helsinn have announced that the first patients have been dosed in a Phase IIa study of elsiglutide (ZP1846) for the prevention of chemotherapy-induced diarrhea in cancer patients. Elsiglutide is a potent and selective glucagon-like-peptide-2 (GLP-2) agonist invented by Zealand Pharma and licensed to Helsinn. Helsinn is also completing a Phase Ib study of elsiglutide in Europe under an Investigational New Drug (IND) with the FDA so far showing that the drug candidate is safe and well tolerated at doses above the expected therapeutic dose in colorectal cancer patients. Elsiglutide is covered by a license agreement between Zealand Pharma and Helsinn Healthcare, under which Helsinn has worldwide exclusive rights to the product in the area of cancer supportive care. Under the agreement, Helsinn is responsible for all further clinical development, regulatory approvals, manufacturing, marketing and sales of elsiglutide, and Zealand Pharma is eligible to milestone payments of up to € 140 million in addition to royalties on sales of elsiglutide. Zealand Pharma holds an option to obtain sales and marketing rights for the product in the Nordic countries. To date, Zealand Pharma has received € 13 (DKK 97) million, of which €3 million were received in December 2011. Zealand Pharma will receive an additional € 1 million in March 2012, relating to Helsinn’s continuously positive development of elsiglutide.
The Phase IIb trial with elsiglutide was conducted at 45 centers across five EU countries (Germany, Czech Republic, Hungary, Poland and Bulgaria), Belarus, Russia and Ukraine and included a total of 497 colorectal cancer patients treated with 5-FU based chemotherapy (FOLFOX or FOLFIRI). Of the total number of patients, 13 received additional treatment with a monoclonal antibody and were not included in the primary trial population. All patients in the trial were randomized to treatment with one of three doses of elsiglutide (10 mg, 20 mg, or 40 mg) or placebo, administered subcutaneously oncedaily over four consecutive days in the first two chemotherapy cycles. All patients were followed for three cycles.
Helsinn has indicated that it is working on potential options for the further development of elsiglutide. The company will evaluate the full set of data generated from the Phase IIb trial and discuss the results with medical experts with the objective of fully understanding the outcome for elsiglutide and evaluate next possible steps.
* On September 30, 2014, Zealand Pharma reports a time-based milestone payment of € 2 (DKK 15) million from its partner Helsinn. The payment relates to the license agreement between Zealand and Helsinn on elsiglutide as a potential first-in-class therapy to prevent chemotherapy-induced diarrhea in cancer patients. Helsinn has evaluated elsiglutide in a Phase IIa trial with supportive results for its effect and safety in the prevention of diarrhea in colorectal cancer patients receiving chemotherapy. Based on these results, Helsinn is now in final preparations for a larger Phase IIb dose-finding trial with planned start of patient dosing at the end of 2014. As part of the elsiglutide development program, Helsinn has also undertaken a large international, multi-center, prospective, cohort observational study in the US and in Europe, to assess the incidence of chemotherapy-induced diarrhea in colorectal and breast cancer patients.
