Agios drops tebapivat in sickle cell disease after Phase 2 misses on differentiation
Hemoglobin response rates of 29.4% to 47.1% across three tebapivat doses landed close to the 33.3% placebo rate, and Agios will not advance the pyruvate kinase activator in sickle cell disease.
Executive Summary
- Agios Pharmaceuticals ended development of tebapivat in sickle cell disease after a Phase 2 dose-finding trial produced hemoglobin response rates that did not separate meaningfully from placebo across three doses tested.
- All three tebapivat doses raised hemoglobin and reduced markers of red blood cell breakdown consistent with the drug's known mechanism, but the response-rate advantage over placebo was inconsistent and did not clear the bar the company had set for continued investment.
- The trial reported on schedule within the second-half-2026 window the company had guided since January, giving Agios a fast, unambiguous answer rather than a delayed or disputed readout.
- Agios's pyruvate kinase activator franchise in sickle cell disease continues through mitapivat, a separate Phase 3 program under FDA Priority Review with a November 1, 2026 decision date, so the mechanism itself is not in question, only this second molecule's competitive fit.
The decision
Agios Pharmaceuticals, Inc. announced on July 21, 2026 that it will not advance tebapivat, an oral pyruvate kinase (PK) activator, in sickle cell disease, citing Phase 2 results that did not establish the differentiation the company said it needed to justify continued development. The trial, registered as NCT06924970, was a dose-finding study designed to characterize tebapivat's dose-response relationship and test whether its profile improved on other PK activators already in the class. The result closed out a catalyst Agios had guided to the second half of 2026 since January, and the readout landed within that window. Agios+2Agios Provides Update on Phase 2 Trial of Tebapivat in Sickle Cell DiseaseJul 21, 2026A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)NCT06924970Agios Outlines 2026 Strategic Priorities and Key Milestones to Accelerate Rare Disease ...Jan 12, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
The design
The trial enrolled 59 patients aged 16 and older with hemoglobin between 5.5 and 10.5 g/dL, randomizing them 2:2:2:1 to once-daily oral tebapivat at 2.5 mg, 5.0 mg, or 7.5 mg, or to placebo, over a 12-week double-blind, placebo-controlled period. The primary endpoint was the percentage of participants achieving a hemoglobin response, defined as at least a 1.0 g/dL increase in average hemoglobin concentration from Weeks 10 through 12 versus baseline. NCT06924970+1A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)NCT06924970Agios Provides Update on Phase 2 Trial of Tebapivat in Sickle Cell DiseaseJul 21, 2026
The result
Response rates were 43.8% (7 of 16) at 2.5 mg, 47.1% (8 of 17) at 5.0 mg, and 29.4% (5 of 17) at 7.5 mg, compared with 33.3% (3 of 9) on placebo. Hemoglobin and hemolysis markers improved across all three tebapivat doses in a pattern consistent with the drug's pyruvate kinase activation mechanism, but the company said the trial did not demonstrate the level of differentiation required to support continued development. "These Phase 2 data further reinforce PK activation as a clinically validated mechanism in sickle cell disease, with tebapivat demonstrating hematologic activity consistent with this class of medicine. However, the results did not establish the level of differentiation we believe is necessary to support continued development," said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D at Agios. Safety and tolerability were consistent with prior sickle cell disease trials of the drug class. AgiosAgios Provides Update on Phase 2 Trial of Tebapivat in Sickle Cell DiseaseJul 21, 2026
What continues
Agios's other pyruvate kinase activator in sickle cell disease, mitapivat, sits in a Phase 3 program (NCT07656415) and is under FDA Priority Review for accelerated approval in sickle cell disease, with a PDUFA goal date of November 1, 2026. Mitapivat and tebapivat share the same PKLR target and modality, making mitapivat the closest comparator to tebapivat within Agios's own pipeline. Beyond Agios, Novo Nordisk's etavopivat, a different pyruvate-kinase-directed small molecule, is in Phase 2 and Phase 3 testing for sickle cell disease, and remains the nearest mechanism-adjacent peer still active in the field. Agios+1Agios Provides Update on Phase 2 Trial of Tebapivat in Sickle Cell DiseaseJul 21, 2026A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)NCT06924970
The field
Sickle cell disease drug development spans several mechanisms beyond PK activation, including Pfizer's Osivelotor, a hemoglobin-modifying oral agent, Fulcrum Therapeutics' Pociredir, a BCL11A-directed program, and gene and cell therapies such as bluebird bio's lovotibeglogene autotemcel, all active in Phase 2 or Phase 3 testing. The pyruvate kinase activator class itself has posted no completed or terminated trials against sickle cell disease before this readout, so tebapivat's exit is the first resolved outcome for a PK activator specifically in this indication, leaving mitapivat's pending Phase 3 result as the mechanism's next test.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.