Tebapivat program terminated
Agios Halts Tebapivat Sickle Cell Program After Phase 2 Trial Lacks Differentiation
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Key Points
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Hb response rates by dose and endpoint definition: In the 12-week phase 2, the Hb response (an increase of at least 1.0 g/dL from baseline during Weeks 10–12) occurred in 2.5 mg group 43.8%, 5.0 mg group 47.1%, and 7.5 mg group 29.4% versus 33.3% for placebo.
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Dosing strategy intended to differentiate tebapivat: the Phase 2 trial used three once-daily dose levels with no dose tapering, aiming for simpler administration than mitapivat, but the results did not demonstrate a sufficient differentiated profile to justify continued development.
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LR-MDS program termination occurred within the same period, signaling a broader pullback on tebapivat across indications (the company had previously ended another tebapivat programme in LR-MDS).
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Mitapivat progress and comparative context: mitapivat remains under FDA review for SCD with a priority/accelerated pathway; in the RISE UP programme mitapivat showed a Hb response but did not reduce vaso-occlusive crises, and the FDA has a target action date of November 1, 2026 for its review.
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Market reaction and investor impact: tebapivat news triggered notable double-digit stock declines, with reports of approximately 14% drop in premarket trading, about 10.7% at the open, and as much as ~18% in some outlets.
Agios Pharmaceuticals is scrapping its tebapivat program for sickle cell disease after a Phase 2 trial failed to set the drug apart from rivals, Biospace reported. The company said the results did not establish a "sufficient differentiated profile" to justify continued investment, ending what was seen as a next-generation bet in the sickle cell space.
Agios shares fell sharply on the news. Premarket trading showed a drop of roughly 14%, with the stock down about 10.7% at the open and as much as 18% in some reports, according to Nasdaq.
Trial Numbers That Failed to Impress Investors
The 12-week Phase 2 trial enrolled 59 patients across three dose groups. Hemoglobin response — defined as a rise of at least 1.0 g/dL from baseline during weeks 10 to 12 — came in at 43.8% for the 2.5 mg dose, 47.1% for the 5.0 mg dose, and 29.4% for the 7.5 mg dose, Benzinga reported. The placebo group hit 33.3%.
The middle dose looked best on paper. But with placebo already clearing one-third of patients, the drug's edge was too thin. Agios said tebapivat's safety profile was consistent with earlier studies, meaning safety was not the problem — differentiation was.
Simpler Dosing Was the Plan, But It Was Not Enough
Tebapivat was designed with a practical edge. The trial used three once-daily doses with no dose tapering, Clinical Trials Arena noted. That simpler schedule was meant to stand out from mitapivat, Agios's other pyruvate kinase activator, which requires a more complex tapering process.
A pyruvate kinase activator works by boosting a key enzyme in red blood cells, helping them survive longer and carry more oxygen. The simpler dosing idea was sound. But when the efficacy data came in flat against placebo, the convenience argument was not enough to save the program.
Tebapivat's Second Failure in Two Months
This is not tebapivat's first exit in 2025. Agios had already ended a separate tebapivat program in low-risk myelodysplastic syndrome, or LR-MDS, just weeks earlier, according to Yahoo Finance. Two discontinuations in two months signals a full retreat from the tebapivat platform across all indications.
The back-to-back failures leave tebapivat without a future at Agios. The company had been developing it as a next-generation follow-up to mitapivat. That strategy is now off the table.
Mitapivat Becomes Agios's Only Sickle Cell Hope
With tebapivat gone, Agios is pointing investors toward mitapivat. The FDA is currently reviewing mitapivat for sickle cell disease with a target action date of November 1, 2026, Biospace reported. The drug received a priority review pathway, which signals regulatory urgency.
Mitapivat is not perfect. In the RISE UP pivotal trials, it showed a clear hemoglobin benefit but did not reduce vaso-occlusive crises — the painful, dangerous blockages in blood vessels that define severe sickle cell disease. That gap may complicate its commercial story even if the FDA approves it.
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