Zealand Pharma Announces Positive Results from Phase 3 Trial of Glepaglutide in Patients with ...

Company announcement – No. 41 / 2022

Zealand Pharma Announces Positive Results from Phase 3 Trial of Glepaglutide in Patients with Short Bowel Syndrome (EASE 1)

• Glepaglutide treatment met the primary endpoint with twice weekly dosing achieving a statistically significant reduction in weekly parenteral support volume by 5.13 Liters/week from baseline at 24 weeks
• 66% of patients in the twice weekly group had a clinically meaningful response (>20% reduction in parenteral support volume)
• In total 9 patients treated with glepaglutide were weaned off parenteral support, while no placebo treated patients were able to wean off parenteral support
• Glepaglutide treatment was assessed as safe and was well-tolerated in the trial
• Conference call scheduled today at 8:00 a.m. ET / 2:00 p.m. CET

Copenhagen, Denmark and Boston MA, U.S. September 30, 2022 – Zealand Pharma A/S (CVR-no. 20045078,) a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced positive topline results from the pivotal Phase 3 trial of glepaglutide, a long-acting GLP-2 analogue designed for once or twice weekly subcutaneous delivery via auto-injector, in patients with short bowel syndrome (SBS).

A total of 106 SBS patients with intestinal failure who were dependent on parenteral support (PS) for at least three days per week were evenly randomized to receive treatment with 10 mg glepaglutide administered either once or twice weekly, or placebo. The primary endpoint in the trial was the absolute change in weekly parenteral support volume from baseline at 24 weeks.

Glepaglutide given twice weekly significantly reduced the total weekly volume of parenteral support at 24 weeks as compared to placebo (p=0.0039). When administered once weekly, glepaglutide treatment also resulted in a numeric reduction in weekly parenteral support, however this did not achieve statistical significance. At 24 weeks, the average reduction in parenteral support from baseline was 5.13 Liters/week for patients treated with glepaglutide twice weekly and was 3.13 Liters/week for patients treated with glepaglutide once weekly. Placebo treatment resulted in a reduction in parenteral support of 2.85 Liters/week.

Clinical response, defined as a patient achieving at least 20% reduction in weekly parenteral support volume from baseline at both 20 and 24 weeks, was significantly higher with twice weekly glepaglutide compared to placebo (p=0.0243). Among patients receiving glepaglutide twice weekly 65.7% achieved a clinical response. While 45.7% and 38.9% of patients achieved a clinical response in the once weekly and placebo treatment groups, respectively.

In the twice weekly dosing group, 14% of patients (n=5) were completely weaned off parenteral support (enteral autonomy). In total 9 patients treated with glepaglutide achieved enteral autonomy, while no placebo treated patients were able to discontinue parenteral support.

 “We are extremely pleased with the results of the Phase 3 EASE 1 trial,” said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. “In EASE 1, glepaglutide significantly reduced the volume of parenteral support required compared to placebo when administered to patients with SBS and intestinal failure. We are particularly encouraged that a number of patients treated with glepaglutide were able to significantly reduce the burden of parenteral support – both reducing the number of days and completely eliminating the need for parenteral support in a substantial number of patients. We believe the outcome of this trial supports the potential of glepaglutide as an effective treatment for people living with SBS and intestinal failure and can reduce the burden of both parenteral support and daily dosing of GLP-2 treatment. We look forward to seeing the results of the ongoing EASE 2 and 3 long term extension trials and engaging with the regulatory authorities as we plan for submission of our NDA.”

Glepaglutide appeared to be safe and was well-tolerated in the trial. The most frequently reported adverse events were injection site reactions and gastrointestinal events. In total, 102 of 106 participating patients completed the trial, of which 96 continued into the ongoing safety and efficacy extension trials, EASE 2 and EASE 3.

“We are enormously privileged to have such a rich pipeline of proprietary peptides that in the last six months have reported two positive Phase 3 trials for two separate programs aimed at changing the lives of patients living with rare and severe diseases,” said Adam Steensberg, M.D., Chief Executive Officer of Zealand Pharma. “Today’s robust results for glepaglutide represent a tremendous milestone for Zealand and patients living with SBS, and we are well-positioned to continue toward delivering next generation peptide therapeutics that make a difference to patients’ lives,”

Conference call today at 2 PM CET / 8 AM ET

Zealand’s management will host a conference call and webcast today at 2:00 pm CET / 8:00 am ET to discuss topline results from the Phase 3 EASE 1 trial followed by a Q&A session. Participating in the call will be Chief Executive Officer, Adam Steensberg, and Chief Medical Officer, David Kendall. The conference call will be conducted in English.

Telephone dial-in information and a unique personal access PIN will be provided upon registration at https://register.vevent.com/register/BI20c985a584b842489c0009561f316e59. A live listen-only audio webcast of the call, including an accompanying slide presentation, will be accessible at https://edge.media-server.com/mmc/p/9n7vxaw3. Participants are advised to register for the call or webcast approximately 10 minutes before the start. A recording of the event will be available following the call on the Investor section of Zealand’s website at https://www.zealandpharma.com/events-cal.

About EASE 1

EASE 1 is a randomized, double-blind Phase 3 trial to evaluate the safety and efficacy of once- and twice-weekly subcutaneous administration of glepaglutide compared to placebo in up to 108 SBS patients with intestinal failure who were dependent on perenteral support (PS) at least three days per week. The trial is designed to confirm the efficacy of glepaglutide in reducing the parenteral PS volume and to evaluate the efficacy of glepaglutide on other efficacy endpoints as well as the safety and tolerability of glepaglutide in patients with SBS. The primary endpoint in the trial is the absolute change in weekly PS volume from baseline at 24 weeks. Participants in EASE 1 may subsequently enroll in the extension trials, EASE 2 and 3, designed to assess long-term safety and efficacy of glepaglutide. EASE 4 is a Phase 3b trial to assess long-term effects of glepaglutide on intestinal fluid and energy uptake. For more information on the EASE trials, please visit ClinicalTrials.gov (IDs: NCT03690206, NCT03905707, NCT04881825, NCT04991311).

About Short Bowel Syndrome

Short Bowel Syndrome (SBS) is a complex chronic and severe condition associated with reduced or complete loss of intestinal function. Many patients have to be connected to infusion lines and pumps every day, which pose significant restrictions on their ability to engage in daily activities. In addition, they are at risk of experiencing a number of serious and life-threatening complications such as sepsis, blood clots, liver damage and renal impairment.

About Glepaglutide

Glepaglutide is a long-acting GLP-2 analog in development as a potential treatment option for short bowel syndrome (SBS). Glepaglutide is being developed as a liquid product in an autoinjector designed for subcutaneous administration, aimed to reduce, or eliminate, the need for parenteral support in people living with SBS. The U.S. Food and Drug Administration (FDA) has granted orphan drug designation for glepaglutide for the treatment of SBS.

About Zealand Pharma A/S 

Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development and partnerships with a number of blue-chip pharma companies as well as commercial partnerships for its marketed products.

Founded in 1998 and headquartered in Copenhagen, Denmark, Zealand has a team in the U.S. For more information about Zealand’s business and activities, please visit http://www.zealandpharma.com.

Forward-Looking Statements

This press release contains “forward-looking statements”, as that term is defined in the Private Securities Litigation Reform Act of 1995, as amended, that provide Zealand Pharma’s expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products. These forward-looking statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented. The reader is cautioned not to rely on these forward-looking statements. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions, which may cause actual results to differ materially from expectations set forth herein and may cause any or all of such forward-looking statements to be incorrect, and which include, but are not limited to, the occurrence of adverse safety events; risks of unexpected costs or delays; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates or expansion of product labelling; failure to obtain regulatory approvals in other jurisdictions; product liability claims; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. If any or all of such forward-looking statements prove to be incorrect, our actual results could differ materially and adversely from those anticipated or implied by such statements. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. All such forward-looking statements speak only as of the date of this press release and are based on information available to Zealand Pharma as of the date of this release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

Contacts:

Anna Krassowska, PhD
Vice President, Investor Relations & Corporate Communications
Zealand Pharma
Email: ank@zealandpharma.com

David Rosen (U.S. Media)
Argot Partners
Email: media@zealandpharma.com