Agios scraps sickle cell program over lackluster Phase 2 data

Agios Pharmaceuticals has decided to discontinue development of its sickle cell disease (SCD) program based on underwhelming Phase 2 data for its next-generation pyruvate kinase (PK) activator, tebapivat.

The Phase 2 trial enrolled 59 patients with SCD who were randomized to one of three once-daily oral doses of tebapivat or placebo for 12 weeks.

The primary endpoint was hemoglobin response (≥1.0 g/dL increase in average hemoglobin from Weeks 10–12 vs baseline). Hemoglobin response rates were 43.8% (2.5 mg), 47.1% (5.0 mg), 29.4% (7.5 mg) for tebapivat, compared with 33.3% for placebo—statistically modest and not clearly differentiated from existing PK activators.

Improvements in hemoglobin and markers of hemolysis were observed, but the trial did not demonstrate a sufficient level of differentiation to justify continued investment in SCD, according to Agios CMO Sarah Gheuens.

The decision follows another recent discontinuation in which Agios halted tebapivat development in lower-risk myelodysplastic syndromes (LR-MDS) after mid-stage data failed to meet predefined efficacy thresholds.

Agios emphasized that PK activation remains a clinically validated mechanism in SCD, but the tebapivat profile did not support further development in this indication.

Following this news, Agios’ shares fell in premarket trading, reflecting investor concerns about the loss of a key pipeline asset in sickle cell disease.