FDA Pushes Agios' Mitapivat SCD Decision to February 2027

The FDA has pushed its decision on Agios Pharmaceuticals' supplemental New Drug Application for mitapivat in sickle cell disease from November 1, 2026, to February 1, 2027, a three-month PDUFA extension triggered by the agency's request for more information on whether a Risk Evaluation and Mitigation Strategy (REMS) is needed. Agios shares fell nearly 18% on Friday, from $37.23 to $30.55.

The extension stems from a major amendment to the sNDA. Agios responded to the FDA on October 19 with roughly nine months of updated safety data, current through October 9, drawn from the open-label extension periods of the Phase II/III RISE UP trial (NCT05031780).

The underlying efficacy picture comes from data published October 24 in The Lancet. In RISE UP, 56 of 138 patients (41%) in the mitapivat arm achieved a hemoglobin response, versus 2 of 69 (3%) on placebo (two-sided p<0.0001). The annualized rate of sickle cell pain crises was 2.6 for mitapivat versus 3.1 for placebo, a difference that did not reach significance (p=0.1213). Serious adverse events occurred in 28 mitapivat patients (20%) versus 20 placebo patients (29%); one event in the mitapivat arm was judged treatment related. Researchers concluded that mitapivat, an oral pyruvate kinase activator, "has the potential to be an effective and convenient disease-modifying treatment for people with sickle cell disease."

Agios said the new safety data continued to show no cases of hepatocellular injury among SCD patients treated with mitapivat, with a pattern and severity similar to those seen in thalassemia trials, and that the risk-benefit profile in SCD is unchanged.

Why did the market react so sharply?

The selloff reflects investor sensitivity to any signal of FDA caution on safety in this population, according to J.P. Morgan biotechnology equity analyst Tessa T. Romero. "Investors were focused on the potential for a REMS in SCD and how the FDA might be considering safety in this patient population, and we see the news being perceived by the market as signaling a more cautious stance from the FDA overall," Romero wrote in a research note, adding that the delay "also seems to be surprising the market."

The timing matters commercially. Investors worry the three-month slip narrows mitapivat's potential first-to-market advantage over Novo Nordisk's SCD candidate etavopivat, which Novo has told investors it will advance to a first regulatory filing in the fourth quarter of this year.

Leerink Partners senior analyst Andrew Berens took a more measured view. "Even if a REMS is necessary, management expects no additional delays and is launch ready. While the extension could delay the commercial launch by ~3 months, management does not believe it changes the commercial opportunity," he wrote. In April, Berens projected a 60% probability of mitapivat reaching the SCD market, with peak US sales of about $550 million.

What is at stake for Agios' portfolio?

Mitapivat is already a commercial product in two indications. Agios has marketed it for thalassemia since January under the name Aqvesme, and it is sold for hemolytic anemia as Pyrukynd. Combined net product revenue for both reached $65.491 million in the first half of this year — 209% above the $21.181 million recorded in January–June 2025. Agios plans to report third-quarter results on Thursday.

Romero flagged the dual challenge facing the company. "We believe Agios is navigating an interesting period, with the Aqvesme launch in thalassemia underway," she wrote. "That said, we struggle to see meaningful near-term upside for the stock and think it may take some time for investors to gain conviction in the launch trajectory of mitapivat in SCD, if/when approved."

The sNDA was filed under the accelerated approval pathway and holds Priority Review. That pathway requires a confirmatory trial, which Agios is running as the Phase III REIGNITE study (NCT07656415). REIGNITE dosed its first patient in July and is designed to demonstrate clinical benefit on transfusion burden in SCD patients aged 12 and older.

Agios said it will continue labeling discussions with the FDA, including elements of a potential REMS. "We have strong conviction in mitapivat's potential to transform care for people living with sickle cell disease, grounded in the comprehensive data from the RISE UP clinical program and further supported by the additional data we submitted in response to the FDA's recent request," CEO Brian Goff said in a statement.

Goff added that the company remains prepared: "We are launch-ready, building on our commercial infrastructure and the strong relationships we have established over several years with hematologists, sickle cell centers, and patients."

Agios will now work toward the new February 1, 2027 action date, with the REMS question — and the etavopivat filing race — set to define the competitive landscape for oral SCD therapy into next year.