Press release - No. 5 / 2022
Zealand Pharma Presents Data from Phase 3 Trial of Dasiglucagon in Congenital Hyperinsulinism at the 60th Annual ESPE Meeting
Dasiglucagon significantly reduced the requirement for intravenous glucose to maintain glycemia in newborns and infants with CHI (Part 1 of Phase 3 trial)
Dasiglucagon reduced time in hypoglycemia and enabled discontinuation of intravenous glucose in most infants and limited the need for pancreatectomy (Part 2 of Phase 3 trial)
Results support the potential for dasiglucagon to be a novel, effective, and well tolerated treatment for infants with CHI dependent on intravenous glucose
Copenhagen, DK and Boston MA, U.S. September 19, 2022 - Zealand Pharma A/S (CVR-no. 20045078,) a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that clinical results from the two-part Phase 3 trial of dasiglucagon for the treatment of congenital hyperinsulinism (CHI) in newborns and infants up to 12 months of age were presented at the 60th annual European Society for Paediatric Endocrinology (ESPE) meeting, held in Rome, September 15-17, 2022. Topline results from Part 1 of the trial were previously announced in May 2022 (Company Announcement No. 22 / 2022).
"Children with CHI can experience significant and permanent neurologic complications as a result of hypoglycemia, and many infants are dependent on intravenous glucose, and in some cases require pancreatectomy, to maintain euglycemia. I am encouraged by the results from Part 1 of this Phase 3 study demonstrating that dasiglucagon treatment resulted in a significant reduction in glucose infusion rate, and to see this trend continue in Part 2, in which the majority of infants could reduce or in many cases be weaned off of IV glucose infusion and also avoid pancreatectomy," said Diva D. De León-Crutchlow, M.D., M.S.C.E., Chief of the Division of Endocrinology and Diabetes and Director of the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia and a study principal investigator. "Though congenital hyperinsulinism is an incredibly challenging disease to manage, the efficacy and safety of dasiglucagon observed in this Phase 3 trial, support its potential as a new treatment option for children with CHI."
"We are very pleased to present the compelling results from the Phase 3 study of dasiglucagon in newborns and infants up to 12 months of age at ESPE 2022. This study deepens our understanding of dasiglucagon's potential as an innovative treatment for CHI patients," said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. "Zealand is committed to addressing the unmet needs of children living with CHI and we look forward to engaging with regulatory authorities and submitting a New Drug Application for dasiglucagon in 2023."
The abstracts of the oral presentations are available at eurospe.org and the data are summarized as follows:
Title: Dasiglucagon Significantly Reduces Requirement for Intravenous Glucose in Children with Congenital Hyperinsulinism ages 7 Days to 12 Months
Authors: Diva D. De Leon, Indraneel Banerjee, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic & Paul S. Thornton
Presentation Highlights: In Part 1 of the Phase 3 trial, dasiglucagon significantly reduced the requirement for intravenous (IV) glucose to maintain glycemia in neonates and infants with CHI and reduced glucose requirements to levels that potentially allow for discontinuation of IV glucose support.
Dasiglucagon significantly reduced the mean IV glucose infusion rate (GIR) in the last 12 hours of the 48 hour treatment period by 55% as compared to placebo (4.3 mg/kg/min for dasiglucagon and 9.4 mg/kg/min for placebo with a treatment difference of 5.2 mg/kg/min; p=0.0037). Dasiglucagon also reduced GIR over the entire 48-hour treatment period by 3.5 mg/kg/min compared to placebo (p=0.0107).
Dasiglucagon treatment resulted in a reduction of 31 g/day in total carbohydrate intake (IV and gastric) compared to placebo (107 g/day for dasiglucagon vs 138 g/day for placebo; p = 0.024), a 22% reduction in carbohydrate calories.
Dasiglucagon was observed to be well tolerated in Part 1 of the trial, with skin reactions and gastrointestinal disturbances as the most frequently reported adverse events (no serious adverse events reported).
Title: Dasiglucagon Treatment Over 21 days in Infants with Congenital Hyperinsulinism Results in Glycaemic Stability and Reduces Requirement for Intravenous Glucose
Authors: Indraneel Banerjee, Diva D. De Leon, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic & Paul S. Thornton
Presentation Highlights: In the 21-day open-label Part 2 of the Phase 3 trial, continuous subcutaneous infusion of dasiglucagon in infants with CHI reduced IV glucose requirements, time in hypoglycaemia and enabled discontinuation of IV glucose in most infants, obviating the need for subtotal pancreatectomy for glycaemic stability.
Dasiglucagon enabled reduction and either periodic or permanent discontinuation of IV glucose infusion in 10 out of 12 infants.
Seven infants, who did not require pancreatectomy, were completely weaned off IV glucose at the completion of the trial.
During the 21-day treatment with dasiglucagon, continuous glucose monitoring (CGM) measures of hypoglycaemia trended lower with median time <70 mg/dL reduced from 7.0% to 5.2% and <54 mg/dL reduced from 1.9% to 0.88%. There was no increase in hyperglycaemia.
The safety profile of dasiglucagon in Part 2 was consistent with Part 1, with no adverse event requiring discontinuation of treatment and no serious adverse events reported.
About the Phase 3 Trial
The Phase 3 trial (17103) was designed to investigate the potential for chronic dasiglucagon infusion, delivered subcutaneously via a pump, to prevent hypoglycemia in newly diagnosed children with CHI who are dependent on intravenous glucose. The trial was conducted in two parts. Part 1 was a double-blind, placebo-controlled two-period crossover with treatment periods of 48 hours each. Part 2 was an open-label, single-arm study of dasiglucagon treatment for an additional 21 days. The primary objective of the overall trial was to reduce or eliminate the need for intensive hospital treatment, reduce the frequency of dangerously low blood glucose (hypoglycemia) and the need for constant feeding, and to potentially delay or eliminate the need for pancreatectomy. (ClinicalTrials.gov: NCT04172441).
About CHI
Congenital hyperinsulinism (CHI) is a rare pediatric disease that affects newborns, infants and children. In CHI the insulin producing cells in the pancreas secrete excess insulin regardless of glucose levels, resulting in severe and recurrent hypoglycemia throughout childhood. Early treatment is necessary to limit the risk of irreversible brain injury and long-term neurologic deficits. Current treatments are limited and may be insufficient to adequately control hypoglycemia.
About Dasiglucagon
Invented by Zealand Pharma, dasiglucagon is a glucagon analog that is stable in aqueous solution and is thus suitable for administration via chronic subcutaneous infusion via pump. In 2017, both the U.S. Food and Drug Administration (FDA) and the European Commission granted orphan drug designation for dasiglucagon for the treatment of CHI.
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.
Contact:
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
Zealand Pharma Presents Data from Phase 3 Trial of Dasiglucagon in Congenital Hyperinsulinism at the 60th Annual ESPE Meeting
Dasiglucagon significantly reduced the requirement for intravenous glucose to maintain glycemia in newborns and infants with CHI (Part 1 of Phase 3 trial)
Dasiglucagon reduced time in hypoglycemia and enabled discontinuation of intravenous glucose in most infants and limited the need for pancreatectomy (Part 2 of Phase 3 trial)
Results support the potential for dasiglucagon to be a novel, effective, and well tolerated treatment for infants with CHI dependent on intravenous glucose
Copenhagen, DK and Boston MA, U.S. September 19, 2022 - Zealand Pharma A/S (CVR-no. 20045078,) a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that clinical results from the two-part Phase 3 trial of dasiglucagon for the treatment of congenital hyperinsulinism (CHI) in newborns and infants up to 12 months of age were presented at the 60th annual European Society for Paediatric Endocrinology (ESPE) meeting, held in Rome, September 15-17, 2022. Topline results from Part 1 of the trial were previously announced in May 2022 (Company Announcement No. 22 / 2022).
"Children with CHI can experience significant and permanent neurologic complications as a result of hypoglycemia, and many infants are dependent on intravenous glucose, and in some cases require pancreatectomy, to maintain euglycemia. I am encouraged by the results from Part 1 of this Phase 3 study demonstrating that dasiglucagon treatment resulted in a significant reduction in glucose infusion rate, and to see this trend continue in Part 2, in which the majority of infants could reduce or in many cases be weaned off of IV glucose infusion and also avoid pancreatectomy," said Diva D. De León-Crutchlow, M.D., M.S.C.E., Chief of the Division of Endocrinology and Diabetes and Director of the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia and a study principal investigator. "Though congenital hyperinsulinism is an incredibly challenging disease to manage, the efficacy and safety of dasiglucagon observed in this Phase 3 trial, support its potential as a new treatment option for children with CHI."
"We are very pleased to present the compelling results from the Phase 3 study of dasiglucagon in newborns and infants up to 12 months of age at ESPE 2022. This study deepens our understanding of dasiglucagon's potential as an innovative treatment for CHI patients," said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. "Zealand is committed to addressing the unmet needs of children living with CHI and we look forward to engaging with regulatory authorities and submitting a New Drug Application for dasiglucagon in 2023."
The abstracts of the oral presentations are available at eurospe.org and the data are summarized as follows:
Title: Dasiglucagon Significantly Reduces Requirement for Intravenous Glucose in Children with Congenital Hyperinsulinism ages 7 Days to 12 Months
Authors: Diva D. De Leon, Indraneel Banerjee, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic & Paul S. Thornton
Presentation Highlights: In Part 1 of the Phase 3 trial, dasiglucagon significantly reduced the requirement for intravenous (IV) glucose to maintain glycemia in neonates and infants with CHI and reduced glucose requirements to levels that potentially allow for discontinuation of IV glucose support.
Dasiglucagon significantly reduced the mean IV glucose infusion rate (GIR) in the last 12 hours of the 48 hour treatment period by 55% as compared to placebo (4.3 mg/kg/min for dasiglucagon and 9.4 mg/kg/min for placebo with a treatment difference of 5.2 mg/kg/min; p=0.0037). Dasiglucagon also reduced GIR over the entire 48-hour treatment period by 3.5 mg/kg/min compared to placebo (p=0.0107).
Dasiglucagon treatment resulted in a reduction of 31 g/day in total carbohydrate intake (IV and gastric) compared to placebo (107 g/day for dasiglucagon vs 138 g/day for placebo; p = 0.024), a 22% reduction in carbohydrate calories.
Dasiglucagon was observed to be well tolerated in Part 1 of the trial, with skin reactions and gastrointestinal disturbances as the most frequently reported adverse events (no serious adverse events reported).
Title: Dasiglucagon Treatment Over 21 days in Infants with Congenital Hyperinsulinism Results in Glycaemic Stability and Reduces Requirement for Intravenous Glucose
Authors: Indraneel Banerjee, Diva D. De Leon, David M. Kendall, Sune Birch, Eva Bøge, Jelena Ivkovic & Paul S. Thornton
Presentation Highlights: In the 21-day open-label Part 2 of the Phase 3 trial, continuous subcutaneous infusion of dasiglucagon in infants with CHI reduced IV glucose requirements, time in hypoglycaemia and enabled discontinuation of IV glucose in most infants, obviating the need for subtotal pancreatectomy for glycaemic stability.
Dasiglucagon enabled reduction and either periodic or permanent discontinuation of IV glucose infusion in 10 out of 12 infants.
Seven infants, who did not require pancreatectomy, were completely weaned off IV glucose at the completion of the trial.
During the 21-day treatment with dasiglucagon, continuous glucose monitoring (CGM) measures of hypoglycaemia trended lower with median time <70 mg/dL reduced from 7.0% to 5.2% and <54 mg/dL reduced from 1.9% to 0.88%. There was no increase in hyperglycaemia.
The safety profile of dasiglucagon in Part 2 was consistent with Part 1, with no adverse event requiring discontinuation of treatment and no serious adverse events reported.
About the Phase 3 Trial
The Phase 3 trial (17103) was designed to investigate the potential for chronic dasiglucagon infusion, delivered subcutaneously via a pump, to prevent hypoglycemia in newly diagnosed children with CHI who are dependent on intravenous glucose. The trial was conducted in two parts. Part 1 was a double-blind, placebo-controlled two-period crossover with treatment periods of 48 hours each. Part 2 was an open-label, single-arm study of dasiglucagon treatment for an additional 21 days. The primary objective of the overall trial was to reduce or eliminate the need for intensive hospital treatment, reduce the frequency of dangerously low blood glucose (hypoglycemia) and the need for constant feeding, and to potentially delay or eliminate the need for pancreatectomy. (ClinicalTrials.gov: NCT04172441).
About CHI
Congenital hyperinsulinism (CHI) is a rare pediatric disease that affects newborns, infants and children. In CHI the insulin producing cells in the pancreas secrete excess insulin regardless of glucose levels, resulting in severe and recurrent hypoglycemia throughout childhood. Early treatment is necessary to limit the risk of irreversible brain injury and long-term neurologic deficits. Current treatments are limited and may be insufficient to adequately control hypoglycemia.
About Dasiglucagon
Invented by Zealand Pharma, dasiglucagon is a glucagon analog that is stable in aqueous solution and is thus suitable for administration via chronic subcutaneous infusion via pump. In 2017, both the U.S. Food and Drug Administration (FDA) and the European Commission granted orphan drug designation for dasiglucagon for the treatment of CHI.
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.
Contact:
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
