Agios pulled the plug on tebapivat in sickle cell disease Tuesday. The oral PK activator couldn’t beat placebo in a Phase 2 study, and it couldn’t beat Agios’s own drugs either.
The 59-patient trial tested three doses over 12 weeks. Hemoglobin response hit 43.8% at 2.5 mg, 47.1% at 5 mg, and 29.4% at 7.5 mg. Placebo response: 33.3%. No dose curve, no separation from noise. Agios called it: not enough differentiation to keep funding it.
The timing is brutal. Novo Nordisk’s etavopivat, a rival once-daily PK activator, just posted a 27% cut in vaso-occlusive crises and a 48.7% hemoglobin response rate in its Phase 3 HIBISCUS trial. Novo plans an FDA filing in the second half of 2026.
Killing tebapivat wasn’t really a strategic call. It’s an admission the PK activator class has a new leader, and it isn’t Agios.
That puts all the weight on mitapivat, Agios’s other PK activator, already marketed as Pyrukynd and Aqvesme. The FDA granted priority review to mitapivat’s sickle cell application, setting a PDUFA date of Nov. 1, 2026, under the accelerated approval pathway. In its own Phase 3 data, mitapivat posted a 40.6% hemoglobin response rate, short of etavopivat’s showing but ahead of what tebapivat managed against placebo.
Agios now has one shot on goal in sickle cell instead of two. Nov. 1 decides whether that shot lands before Novo’s filing catches up.
— Sarah Chen