Agios Pharmaceuticals has opted to terminate the development programme for its sickle cell disease (SCD) candidate, tebapivat, as the company claims the drug failed to establish a “differentiated profile” in the inherited blood disorder.
This follows middle-of-the-road Phase II results for the oral pyruvate kinase activator, in which a once daily, 5mg dose of the drug triggered a haemoglobin response in eight of the 17 patients (47.1%) receiving this dose at week 12, while three out of the nine in the placebo group achieved the same feat. Researchers defined patients as having a haemoglobin response if they experienced an increase in blood concentration from baseline of at least 1.0g/dL between weeks 10 and 12 of the study.
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The 2.5mg and 7.5mg dosing arms showed lower patient haemoglobin responses compared with the 5mg cohort, with seven of 16 (43.8%) and five of the 17 patients (29.4%) crossing the response threshold.
Patients with SCD tolerated the drug well.
While Agios’ CMO and head of R&D, Sarah Gheuens, claimed that the tebapivat readout strengthens the argument that pyruvate kinase activation is a clinically validated mechanism in SCD, she caveated that the results failed to establish “the level of differentiation” the company believes is suitable to support tebapivat’s continued development.
This deals a final blow to tebapivat’s future prospects, as the company previously chose to end the only other publicly disclosed development programme for the drug in low-risk forms of the rare blood cancer, myelodysplastic syndrome (MDS), following its lacklustre efficacy in a Phase IIb trial.
This result appears to have spooked investors, as Agios’ stock value sank 10.7% from $40.06 at market close on 20 July to $35.77 at market open on 21 July. Agios trades on the Nasdaq with a market cap of $2.38bn.
While Agios will endure a notable blow from tebapivat’s SCD termination, the company is still pinning hopes on its marketed thalassaemia-linked anaemia drug, Aqvesme (mitapivat) in SCD, which US regulators are currently reviewing for a potential accelerated approval. The US Food and Drug Administration (FDA) has set the target decision date for mitapivat in SCD to 1 November 2026.
SCD’s therapeutic revolution
In recent years, there have been several drugs that have secured the regulatory greenlight in SCD – breaking the near two decades-long dormancy the field faced between the first approval of hydroxyurea in 1998 and the second obtained by Emmaus Life Sciences’ Endari (L-glutamine) in 2017.
Since Endari’s market debut, several drugs have hit the SCD market. This includes one-time, cell-based gene therapies like Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy (exagamglogene autotemcel), as well as Minaris and Genetix Biotherapeutics’ (previously Bluebird Bio) Lyfgenia (lovotibeglogene autotemcel).
As therapeutic options for SCD continue to see uptake, there are also several drugs in development for the blood disorder. According to GlobalData’s Pharmaceutical Intelligence Center, just under one in five of the ongoing studies focused on SCD are in Phase III, while Phase II remains the most populated stage of development within this condition.
GlobalData is the parent company of Clinical Trials Arena.
