Agios shares slump on sickle cell disease data

Shares in Agios Pharma lost nearly half their value in pre-market trading today after it posted mixed clinical results from a phase 3 trial of its sickle cell disease (SCD) therapy mitapivat, sending its investors into a spin.

In the pivotal RISE UP study, mitapivat – an orally-active pyruvate kinase (PKR) activator – was able to achieve a significant improvement compared to placebo on one of its primary endpoints, the haemoglobin response, which was defined as a 1.0 g/dL increase or more in haemoglobin concentration from week 24 to week 52 compared to baseline.

However, mitapivat was unable to hit the mark in the trial's second and arguably most clinically important primary endpoint, as it failed to achieve a significant improvement over placebo in 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 also missed the mark in one key secondary endpoint – the change from baseline in the PROMIS fatigue scale – although, that was achieved in the group of patients who had a haemoglobin response. Finally, the safety of the drug was "consistent with that observed in prior [...] studies," said Agios.

Despite the mixed data, the company remains determined to file mitapivat for approval with the FDA, seeking to extend its label beyond the treatment of haemolytic anaemia in adults with rare disorder pyruvate kinase (PK) deficiency, for which it is sold as Pyrukynd.

Agios has also filed for approval of the drug in thalassaemia, another blood disorder, and is hoping for a positive verdict from the FDA before the end of the year.

Agios' positive assessment of the SCD data did not stop some investors from losing their nerve, however, and Agios' shares were trading down a little over 49% at the time of writing.

That reaction reflects that around 100,000 people are living with SCD in the US, compared to a few thousand with thalassaemia and an estimated 1,000 to 2,000 with PK deficiency. Sales of Pyrukynd in its current indication are running at around $13 million a quarter.

Agios' main rival in the oral PKR activator category is Novo Nordisk, which acquired rival pyruvate kinase R activator etavopivat when it bought Forma Therapeutics for $1.1 billion three years ago.

Novo Nordisk is testing etavopivat in three phase 3 trials, namely HIBISCUS and HIBISCUS-2 in SCD and FLORAL in patients with SCD and thalassaemia, another blood disorder. Results from HIBISCUS are due next year.

"Sickle cell disease is a complex and devastating condition that has long lacked innovation," said RISE UP investigator Biree Andemariam, of University of Connecticut Health.

"As a result, patients have very few effective treatments, contributing to poor outcomes and shortened lifespans," she added. "These strong results, coupled with a favourable safety profile, support the potential of mitapivat as a novel treatment option."

Agios said it is hoping to meet with the FDA to discuss the SCD filing in the first quarter of 2026.