Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes
New England Journal of Medicine, vol. 393, pp. 858–868
Abstract
BACKGROUND: Zimislecel is an allogeneic stem cell-derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. METHODS: cells) as a single infusion. All the participants also received glucocorticoid-free immunosuppressive therapy. The primary end point in part A was safety. The primary end point in part C was freedom from severe hypoglycemic events during days 90 through 365, with a glycated hemoglobin level of less than 7% or a decrease of at least 1 percentage point from baseline in the glycated hemoglobin level at one or more time points between days 180 and 365. Secondary end points in part C included safety and insulin independence between days 180 and 365. Assessment of the primary and secondary end points in part C involved the participants who received the full dose of zimislecel as a single infusion in part B or C. Detection of serum C-peptide during a 4-hour mixed-meal tolerance test was used to assess engraftment and islet function. All the analyses were interim and not prespecified. RESULTS: A total of 14 participants (2 in part A and 12 in parts B and C) completed at least 12 months of follow-up and were included in the analyses. C-peptide was undetectable at baseline in all 14 participants. After zimislecel infusion, all the participants had engraftment and islet function, as evidenced by the detection of C-peptide. Neutropenia was the most common serious adverse event, occurring in 3 participants. Two deaths occurred - one caused by cryptococcal meningitis and one by severe dementia with agitation owing to the progression of preexisting neurocognitive impairment. All 12 participants in parts B and C were free of severe hypoglycemic events and had a glycated hemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter). Ten of the 12 participants (83%) had insulin independence and were not using exogenous insulin at day 365. CONCLUSIONS: The results of this small, short-term study involving persons with type 1 diabetes support the hypothesis that zimislecel can restore physiologic islet function, warranting further clinical investigation. (Funded by Vertex Pharmaceuticals; VX-880-101 FORWARD ClinicalTrials.gov number, NCT04786262.).
Authors 20
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University Health Network · University of Toronto · Toronto General Hospital
Affiliation as printed
Toronto General Hospital, University Health Network, University of Toronto, Toronto
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Affiliation as printed
University of Pennsylvania Perelman School of Medicine, Philadelphia
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University of Wisconsin–Madison
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University of Wisconsin, Madison
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University of Chicago, Chicago
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Affiliation as printed
University of Chicago, Chicago
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University of Pittsburgh Medical Center
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University of Pittsburgh Medical Center, Pittsburgh
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City Of Hope National Medical Center
Affiliation as printed
City of Hope National Medical Center, Duarte, CA
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Eelco J.P. de Koning Aachen
Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Leiden, the Netherlands
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University of Southern California
Affiliation as printed
University of Southern California, Los Angeles
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Affiliation as printed
Katholieke Universiteit Leuven, Leuven, Belgium
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Boston Children's Hospital · Dana-Farber Cancer Institute
Affiliation as printed
Dana–Farber Cancer Institute–Boston Children’s Hospital, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Vertex Pharmaceuticals (United States)
Affiliation as printed
Vertex Pharmaceuticals, Boston
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Affiliation as printed
University of Miami, Miami
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Affiliation as printed
University of Pennsylvania Perelman School of Medicine, Philadelphia
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