Agios Pharmaceuticals announced on July 21 that it is discontinuing development of its next-generation PK activator, tebapivat, following midstage data in sickle cell disease that did not differentiate the asset from others in development. The decision comes after a Phase 2 study involving 59 patients aged 16 and older showed that daily doses of tebapivat resulted in a hemoglobin response—the primary endpoint—for 43.8% of patients at the 2.5 mg dose, 47.1% at the 5 mg dose, and 29.4% at the 7.5 mg dose, compared to a response rate of 33.3% for placebo.
The company said these findings failed to demonstrate a clear dose response and did not meet Agios’ criteria for continued development in sickle cell disease. Tebapivat is not being tested for any other indications according to Agios’ online pipeline.
Meanwhile, Novo Nordisk’s investigational once-daily PK activator etavopivat led to a hemoglobin response in 48.7% of patients after 24 weeks in the Phase 3 HIBISCUS trial and elicited a reported drop of vaso-occlusive crises by 27%. Novo Nordisk plans to submit etavopivat for FDA approval later this year.
Analysts reacted calmly to Agios’ announcement about tebapivat’s discontinuation. Leerink Partners wrote Tuesday that they had not included tebapivat in their financial model, so their outlook remains unchanged. However, analysts noted that the move increases pressure on Agios’ other assets such as mitapivat—an oral PK activator currently under FDA review for sickle cell disease—which demonstrated a hemoglobin response rate of 40.6% in its own Phase 3 trial.
Mitapivat already has marketing approval under different brand names for pyruvate kinase deficiency and anemia associated with alpha- or beta-thalassemia. Leerink Partners said, “We believe the update places greater importance on the commercial execution of mitapivat in thalassemia, a smooth regulatory review for mitapivat in SCD, the early pipeline (e.g., AG-181 in phenylketonuria, AG-236 in polycythemia vera), and any potential business development opportunities.”
Truist analysts agreed with this assessment: “The discontinuation does remove AGIO’s second shot on goal in SCD, and puts more concentration risk on mitapivat, which to us could be relevant at a time when the bar for differentiation in the class continues to rise.”
