Agios mulls early FDA filing for sickle cell therapy

 Agios is planning to file its sickle cell disease (SCD) candidate mitapivat with the FDA under the accelerated pathway, based on feedback from the US regulator at a recent meeting.

The decision has come despite mixed results in the phase 3 RISE UP trial of the orally-active pyruvate kinase (PKR) activator, reported last November, which led to a big fall in the company's share price.

Agios said it has submitted the protocol for a proposed confirmatory trial of mitapivat for consideration by the FDA as it works towards an accelerated approval application "in the coming months."

Shares in the company rose around 20% to more than $34 after the announcement, regaining a sizeable chunk of the territory last after the RISE UP data reveal, when it was trading above $45.

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.

Agios presented the RISE UP results and data from its phase 3 programme for mitapivat at the FDA meeting, according to the company, adding that, "based on the discussion, the FDA recommended submission of a proposal for a confirmatory clinical trial to support US accelerated approval."

The US regulator has been talking a lot about exercising regulatory flexibility to make potentially clinically important new drugs available more quickly to patients, particularly for rare diseases, whilst still adhering to its obligation to approve drugs based on "substantial evidence" of effectiveness.

"Our engagements with the FDA continue to underscore both the unmet need in sickle cell disease and the importance of expeditiously advancing new treatment options for patients living with this complex, debilitating, and deadly disease," said Agios' chief medical officer, Sarah Gheuens.

The company said it has proposed a primary endpoint that is different from the one used in the RISE UP clinical programme, and it remains to be seen whether its suggestion will be accepted by the regulator.

Mitapivat has been approved in the US under the Pyrukynd trade name since 2022 as a treatment for haemolytic anaemia in adults with pyruvate kinase (PK) deficiency, and late last year claimed another approval – as Aqvesme – for anaemia associated with alpha- or beta-thalassaemia.

An 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.

Agios reported $54 million in revenues from Pyrukynd last year, up 48% on the prior year.

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