Mitapivat in Sickle Cell Disease (RISE UP): Phase 3 Global Randomised Trial Reported in Lancet

Trial design and global scope

The Lancet article title and citation identify the study as a phase 3, double-blind, global, randomised, placebo-controlled trial of mitapivat in sickle cell disease called RISE UP. That trial classification implies a late-stage, confirmatory randomized design with placebo control and blinding, and the authorship list indicates enrolment across multiple regions. The PubMed excerpt provided confirms international participation but does not include the detailed protocol, such as eligibility criteria, dosing schedule, treatment duration, statistical plan, or predefined primary and secondary endpoints. The source text therefore documents study phase and design label only; specific methodological parameters were not reported in the supplied excerpt.

Authorship and participating centres

The investigators reported on RISE UP with a large, geographically diverse authorship. Lead and contributing authors include clinicians and researchers from the United States, Canada, Europe, the Middle East, Africa, and Latin America. The PubMed excerpt lists institutional affiliations for each named author—centres such as the New England Sickle Cell Institute, University of Toronto, University Medical Center Utrecht, and multiple specialty haematology units—as well as multiple contributors from Agios Pharmaceuticals. This distribution signals a multicentre effort and industry collaboration, but the supplied content does not list site-level enrollment numbers or confirm the total number of participating centres.

Publication identifiers and citation details

The Lancet citation provided in the PubMed entry is complete for bibliographic purposes: volume 408, issue 10565, pages 1705–1716; publication date 24 Oct 2026; DOI 10.1016/S0140-6736(26)01480-7; PubMed ID 42913682. Those identifiers allow direct retrieval of the full paper. The excerpt also displays the clinical-trial label in the article metadata and confirms that the report appears in a peer-reviewed, high-impact journal. Beyond these bibliographic details, the supplied text does not reproduce the article abstract or full text results.

Available report content versus missing outcome data

The PubMed excerpt supplies the article title, complete author list, institutional affiliations, journal citation, DOI, and PMID. Investigators are named and institutions mapped. However, the excerpt does not provide the trial’s numerical outcomes, efficacy signals, safety and tolerability data, adverse-event profiles, primary endpoint achievement, p values, confidence intervals, subgroup analyses, or regulatory interpretations. The supplied source therefore lacks the essential result figures and statistical summaries that clinicians and guideline committees rely on for assessment. Any statement about efficacy magnitude, responder rates, effect on vaso-occlusive crises, haemoglobin changes, or safety events would require consulting the full Lancet article; such specifics are not present in the PubMed snippet used for this rewrite.

Key unanswered clinical questions from the supplied excerpt

Investigators reported the existence of a global phase 3 RISE UP trial of mitapivat in sickle cell disease, but the following items were not reported in the provided PubMed text and remain unanswered here:

• What was the trial’s primary endpoint and did the trial meet it? The excerpt does not report endpoint definitions or outcome results.
• What were the numerical efficacy results and their statistical significance? No effect sizes, rates, or p values are present in the supplied content.
• What safety signals or adverse-event rates emerged during the study? The excerpt lacks any safety or tolerability data.
• How many patients were randomized, and what were the key baseline characteristics or subgroup findings? Sample size and demographic or genotype breakdowns were not included.
• What dosing regimen of mitapivat was used, and for what treatment duration? Dosing and exposure details are not reported in the excerpt.

Readers seeking clinical interpretation or application should consult the full Lancet article via the DOI or PubMed ID provided; the PubMed entry used for this summary furnishes bibliographic and authorship information only. The limitations of the supplied text preclude any evidence-based statements about the clinical efficacy or safety profile of mitapivat in sickle cell disease from this excerpt alone.