---
title: "Mitapivat in Sickle Cell Disease (RISE UP): Phase 3 Global Randomised Trial Reported in Lancet"
id: "pubmed-42913682"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42913682"
content_type: "clinical_feed_article"
specialty: "Hematology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42913682/"
doi: "10.1016/S0140-6736(26)01480-7"
published_at: "2026-10-24T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Mitapivat in Sickle Cell Disease (RISE UP): Phase 3 Global Randomised Trial Reported in Lancet
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42913682
- **Specialty:** [Hematology](https://medichelpline.com/clinical-feed/hematology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42913682/)
- **DOI:** [10.1016/S0140-6736(26)01480-7](https://doi.org/10.1016%2FS0140-6736(26)01480-7)
- **Published At:** 2026-10-24T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The trial was a **phase 3**, double-blind, global, randomised, placebo-controlled study of **mitapivat** in **sickle cell disease**; this description comes from the article title and citation only. - Investigators listed include a broad, international authorship team across North America, Europe, Africa, the Middle East, and industry contributors from Agios Pharmaceuticals. - The Lancet citation and identifiers provided were: PMID 42913682 and DOI 10.1016/S0140-6736(26)01480-7; publication details show volume 408, pages 1705–1716, dated 24 Oct 2026. - The source text available to this rewrite did not include the trial’s primary or secondary endpoint data, numerical efficacy outcomes, statistical analyses, or safety results; those specifics were not reported in the supplied excerpt. - The provided content lists institutional affiliations and many named authors, indicating multicentre participation, but the source did not report sample size, inclusion criteria, dosing regimen, duration, or key efficacy and adverse-event findings. - Readers are directed to the Lancet article for full results; the available PubMed excerpt supplies bibliographic and authorship information but lacks trial outcome data necessary for clinical interpretation. - The absence of reported outcomes in the supplied source means no inferences about clinical effect size, significance, or regulatory implication can be drawn from this text alone.
## Clinical Analysis & Structured Key Points
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Electronic address: andemariam@uchc.edu."), [Kevin H M Kuo](https://pubmed.ncbi.nlm.nih.gov/?term=Kuo+KHM&cauthor_id=42913682)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-2 "University of Toronto, Toronto, ON, Canada; Scarborough Health Network Research Institute, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada."), [Farjah H Algahtani](https://pubmed.ncbi.nlm.nih.gov/?term=Algahtani+FH&cauthor_id=42913682)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-3 "Oncology Centre, Section of Adult Hematology/HSCT, Epidemiology and Public Health Research Chair, King Saud University, King Saud Medical City, Riyadh, Saudi Arabia."), [Salam Al Kindi](https://pubmed.ncbi.nlm.nih.gov/?term=Al+Kindi+S&cauthor_id=42913682)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-4 "Department of Hematology, Sultan Qaboos University, Muscat, Oman."), [Kenneth I Ataga](https://pubmed.ncbi.nlm.nih.gov/?term=Ataga+KI&cauthor_id=42913682)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-5 "University of Tennessee Health Science Center, Memphis, TN, USA."), [Pablo Bartolucci](https://pubmed.ncbi.nlm.nih.gov/?term=Bartolucci+P&cauthor_id=42913682)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-6 "Reference Center of Sickle Cell Disease, Mondor University Hospital, Créteil, France."), [Andrew Campbell](https://pubmed.ncbi.nlm.nih.gov/?term=Campbell+A&cauthor_id=42913682)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-7 "Division of Hematology, Children's National Hospital, Washington, DC, USA."), [Raffaella Colombatti](https://pubmed.ncbi.nlm.nih.gov/?term=Colombatti+R&cauthor_id=42913682)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-8 "Department of Woman's and Child's Health, University of Padova, Padova, Italy."), [Alexander K Glaros](https://pubmed.ncbi.nlm.nih.gov/?term=Glaros+AK&cauthor_id=42913682)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-9 "Central Michigan University, Children's Hospital of Michigan, Detroit, MI, USA."), [Kaoutar Hafraoui](https://pubmed.ncbi.nlm.nih.gov/?term=Hafraoui+K&cauthor_id=42913682)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-10 "Hematology, CHU Liège, Liège, Belgium."), [Modupe Idowu](https://pubmed.ncbi.nlm.nih.gov/?term=Idowu+M&cauthor_id=42913682)[ 11 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-11 "McGovern Medical School, UTHealth, Houston, TX, USA."), [Seethal A Jacob](https://pubmed.ncbi.nlm.nih.gov/?term=Jacob+SA&cauthor_id=42913682)[ 12 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-12 "Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA."), [Clarisse L C Lobo](https://pubmed.ncbi.nlm.nih.gov/?term=Lobo+CLC&cauthor_id=42913682)[ 13 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-13 "Research Division, HEMORIO, Rio de Janeiro, Brazil."), [Obiageli E Nnodu](https://pubmed.ncbi.nlm.nih.gov/?term=Nnodu+OE&cauthor_id=42913682)[ 14 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-14 "Department of Hematology and Blood Transfusion, Centre of Excellence for Sickle Cell Disease Research and Training, College of Health Sciences, University of Abuja, Abuja, Nigeria."), [Lucas Otieno](https://pubmed.ncbi.nlm.nih.gov/?term=Otieno+L&cauthor_id=42913682)[ 15 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-15 "Victoria Biomedical Research Institute, Kisumu, Kenya."), [Wally R Smith](https://pubmed.ncbi.nlm.nih.gov/?term=Smith+WR&cauthor_id=42913682)[ 16 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-16 "Virginia Commonwealth University, Richmond, VA, USA."), [Swee Lay Thein](https://pubmed.ncbi.nlm.nih.gov/?term=Thein+SL&cauthor_id=42913682)[ 17 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-17 "Sickle Cell Branch, The National Heart, Lung, and Blood Institute, Bethesda, MD, USA."), [Eduard J van Beers](https://pubmed.ncbi.nlm.nih.gov/?term=van+Beers+EJ&cauthor_id=42913682)[ 18 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-18 "University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands."), [Sarah Gheuens](https://pubmed.ncbi.nlm.nih.gov/?term=Gheuens+S&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Brooke Hensley](https://pubmed.ncbi.nlm.nih.gov/?term=Hensley+B&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Abdulafeez Oluyadi](https://pubmed.ncbi.nlm.nih.gov/?term=Oluyadi+A&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Kareem Osman](https://pubmed.ncbi.nlm.nih.gov/?term=Osman+K&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Asif Pathan](https://pubmed.ncbi.nlm.nih.gov/?term=Pathan+A&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Spurthi Patil](https://pubmed.ncbi.nlm.nih.gov/?term=Patil+S&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Tao Song](https://pubmed.ncbi.nlm.nih.gov/?term=Song+T&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Amber M Yates](https://pubmed.ncbi.nlm.nih.gov/?term=Yates+AM&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Ahmar U Zaidi](https://pubmed.ncbi.nlm.nih.gov/?term=Zaidi+AU&cauthor_id=42913682)[ 19 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-19 "Agios Pharmaceuticals, Cambridge, MA, USA."), [Caterina Minniti](https://pubmed.ncbi.nlm.nih.gov/?term=Minniti+C&cauthor_id=42913682)[ 20 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-20 "Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA."), [Miguel R Abboud](https://pubmed.ncbi.nlm.nih.gov/?term=Abboud+MR&cauthor_id=42913682)[ 21 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#full-view-affiliation-21 "Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon."); [RISE UP Investigators](https://pubmed.ncbi.nlm.nih.gov/?term=RISE+UP+Investigators%5BCorporate+Author%5D) Affiliations Expand ### Affiliations * 1 New England Sickle Cell Institute, University of Connecticut Health, Farmington, CT, USA. Electronic address: andemariam@uchc.edu. * 2 University of Toronto, Toronto, ON, Canada; Scarborough Health Network Research Institute, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada. * 3 Oncology Centre, Section of Adult Hematology/HSCT, Epidemiology and Public Health Research Chair, King Saud University, King Saud Medical City, Riyadh, Saudi Arabia. * 4 Department of Hematology, Sultan Qaboos University, Muscat, Oman. * 5 University of Tennessee Health Science Center, Memphis, TN, USA. * 6 Reference Center of Sickle Cell Disease, Mondor University Hospital, Créteil, France. * 7 Division of Hematology, Children's National Hospital, Washington, DC, USA. * 8 Department of Woman's and Child's Health, University of Padova, Padova, Italy. * 9 Central Michigan University, Children's Hospital of Michigan, Detroit, MI, USA. * 10 Hematology, CHU Liège, Liège, Belgium. * 11 McGovern Medical School, UTHealth, Houston, TX, USA. * 12 Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA. * 13 Research Division, HEMORIO, Rio de Janeiro, Brazil. * 14 Department of Hematology and Blood Transfusion, Centre of Excellence for Sickle Cell Disease Research and Training, College of Health Sciences, University of Abuja, Abuja, Nigeria. * 15 Victoria Biomedical Research Institute, Kisumu, Kenya. * 16 Virginia Commonwealth University, Richmond, VA, USA. * 17 Sickle Cell Branch, The National Heart, Lung, and Blood Institute, Bethesda, MD, USA. * 18 University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. * 19 Agios Pharmaceuticals, Cambridge, MA, USA. * 20 Montefiore Medical Center, Albert Einstein College of Medicine, New York, NY, USA. * 21 Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon. * PMID: **42913682** * DOI: [ 10.1016/S0140-6736(26)01480-7 ](https://doi.org/10.1016/s0140-6736\(26\)01480-7) Item in Clipboard Clinical Trial # Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial Biree Andemariam et al. Lancet. 2026. Show details Display options Display options Format Abstract PubMed PMID Lancet Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Lancet%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Lancet%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42913682/) . 2026 Oct 24;408(10565):1705-1716. doi: 10.1016/S0140-6736(26)01480-7. ### Authors [Biree Andemariam](https://pubmed.ncbi.nlm.nih.gov/?term=Andemariam+B&cauthor_id=42913682)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-1 "New England Sickle Cell Institute, University of Connecticut Health, Farmington, CT, USA. Electronic address: andemariam@uchc.edu."), [Kevin H M Kuo](https://pubmed.ncbi.nlm.nih.gov/?term=Kuo+KHM&cauthor_id=42913682)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-2 "University of Toronto, Toronto, ON, Canada; Scarborough Health Network Research Institute, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada."), [Farjah H Algahtani](https://pubmed.ncbi.nlm.nih.gov/?term=Algahtani+FH&cauthor_id=42913682)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-3 "Oncology Centre, Section of Adult Hematology/HSCT, Epidemiology and Public Health Research Chair, King Saud University, King Saud Medical City, Riyadh, Saudi Arabia."), [Salam Al Kindi](https://pubmed.ncbi.nlm.nih.gov/?term=Al+Kindi+S&cauthor_id=42913682)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-4 "Department of Hematology, Sultan Qaboos University, Muscat, Oman."), [Kenneth I Ataga](https://pubmed.ncbi.nlm.nih.gov/?term=Ataga+KI&cauthor_id=42913682)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-5 "University of Tennessee Health Science Center, Memphis, TN, USA."), [Pablo Bartolucci](https://pubmed.ncbi.nlm.nih.gov/?term=Bartolucci+P&cauthor_id=42913682)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-6 "Reference Center of Sickle Cell Disease, Mondor University Hospital, Créteil, France."), [Andrew Campbell](https://pubmed.ncbi.nlm.nih.gov/?term=Campbell+A&cauthor_id=42913682)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-7 "Division of Hematology, Children's National Hospital, Washington, DC, USA."), [Raffaella Colombatti](https://pubmed.ncbi.nlm.nih.gov/?term=Colombatti+R&cauthor_id=42913682)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-8 "Department of Woman's and Child's Health, University of Padova, Padova, Italy."), [Alexander K Glaros](https://pubmed.ncbi.nlm.nih.gov/?term=Glaros+AK&cauthor_id=42913682)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-9 "Central Michigan University, Children's Hospital of Michigan, Detroit, MI, USA."), [Kaoutar Hafraoui](https://pubmed.ncbi.nlm.nih.gov/?term=Hafraoui+K&cauthor_id=42913682)[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-10 "Hematology, CHU Liège, Liège, Belgium."), [Modupe Idowu](https://pubmed.ncbi.nlm.nih.gov/?term=Idowu+M&cauthor_id=42913682)[ 11 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-11 "McGovern Medical School, UTHealth, Houston, TX, USA."), [Seethal A Jacob](https://pubmed.ncbi.nlm.nih.gov/?term=Jacob+SA&cauthor_id=42913682)[ 12 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-12 "Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA."), [Clarisse L C Lobo](https://pubmed.ncbi.nlm.nih.gov/?term=Lobo+CLC&cauthor_id=42913682)[ 13 ](https://pubmed.ncbi.nlm.nih.gov/42913682/#short-view-affiliation-13 "Research Division, HEMORIO, Rio de Janeiro, Brazil."), [Obiageli E Nnodu](https://pubmed.ncbi.nlm.nih.gov/?term=Nnodu+OE&cauthor_id=42913682)[ 14 ](https://pubmed.ncbi.nlm.nih.go
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