Agios shares slide as it abandons sickle cell candidate
Agios Pharma has said it will halt clinical development of tebapivat, a PK activator that had reached phase 2 testing in sickle cell disease, after preliminary results proved disappointing.
Shares in the company were down almost 18% on the announcement, which said the haemoglobin response rate data observed with tebapivat "were consistent with the class of medicine" but did not establish a "differentiated profile" in SCD.
Agios' lead PK activator – mitapivat – is already under regulatory review by the FDA as a first-in-class treatment for SCD on the back of data from the RISE UP trial, with a decision by the US agency on an accelerated approval due by 1st November.
In the phase 3 trial, mitapivat was shown to achieve a significant improvement compared to placebo on the haemoglobin response, a primary endpoint, but was unable to improve the annualised rate of sickle cell vaso-occlusive crises (VOCs) – the excruciatingly painful attacks that occur when red blood cells become misshapen and block blood vessels.
Mitapivat targets the PKR isoform of the pyruvate kinase (PK) enzyme, while tebapivat was billed as a next-generation drug, designed to activate both PKR and PKM2 isoforms, that Agios had hoped would give it "broader reach" in SCD. It also offered simpler dosing, without the dose-tapering needed with mitapivat.
As it turned out, the 12-week phase 2 trial, which compared three doses of tebapivat to placebo, did show improvements in haemoglobin levels and haemolysis. However, the primary endpoint of a haemoglobin response was achieved in 29% to 47% of patients with the PK activator, compared to 33% with placebo.
That was not far away from the haemoglobin response seen in RISE UP at 52 weeks – which came in at around 41%, while the placebo response was much lower at only 3% – but Agios said the results "did not demonstrate the level of differentiation required to support continued development."
Mitapivat has been approved in the US under the Pyrukynd trade name since 2022 as a treatment for haemolytic anaemia in adults with PK deficiency, and late last year claimed another approval – as Aqvesme – for anaemia associated with alpha- or beta-thalassaemia.
Sales of Pyrukynd were $54 million in 2025, and approval in SCD would transform the sales potential for the drug, as around 100,000 people are living with SCD in the US, compared to around 4,000 with thalassaemia and an estimated 1,000 to 2,000 with PK deficiency.
"We look forward to bringing this first-in-class medicine to the sickle cell community and building on the extensive clinical experience generated to date as we work to address the significant unmet need in this debilitating disease," said Sarah Gheuens, Agios' chief medical officer.
