The FDA has delayed a decision on Agios Pharmaceuticals’ supplemental New Drug Application (sNDA) seeking additional approval for mitapivat in sickle cell disease (SCD) until next year. The FDA has extended its target action date under the Prescription Drug User Fee Act (PDUFA) by three months, from the originally scheduled November 1, 2026, to February 1, 2027, Agios acknowledged in a statement.
Investors punished Agios with a stock selloff that sent the company’s share price slumping nearly 18% from $37.23 to $30.55 on Friday.
The three-month extension was triggered by what the FDA deemed a major amendment to the sNDA—namely the submission, at the agency’s request, of additional information to assess whether a Risk Evaluation and Mitigation Strategy (REMS) would be necessary for mitapivat in SCD.
Agios responded to the FDA on October 19 by submitting approximately nine months of updated safety data through October 9 from the ongoing open-label extension periods of the Phase II/III RISE UP trial (NCT05031780).
According to data published October 24 in The Lancet, 56 (41%) of 138 patients in the mitapivat group showed a hemoglobin response, compared with two (3%) of 69 patients on placebo (95% CI; two-sided p<0·0001). The annualized rate (95% CI) of sickle cell pain crises was 2.6 for mitapivat compared with 3.1 for placebo (two-sided p=0.1213). Serious adverse events were reported in 28 (20%) patients on mitapivat vs. 20 (29%) patients on placebo; one mitapivat patient’s event was deemed treatment related.
Mitapivat, an oral pyruvate kinase activator, “has the potential to be an effective and convenient disease-modifying treatment for people with sickle cell disease, researchers concluded in the study.
The new data, Agios said, continued to show no cases of hepatocellular injury (HCI) among patients with SCD treated with mitapivat who showed a pattern and severity similar to those observed trials for mitapivat in adults with thalassemia, Agios stated, adding that the risk-benefit profile of mitapivat in SCD remained unchanged.
“More cautious stance”
“Based on our recent conversations/inbounds, 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,” Tessa T. Romero, a senior analyst focused on biotechnology equity research with J.P. Morgan, wrote in a research note.
Romero added that the delay “also seems to be surprising the market,” as Agios investors are concerned the agency’s action narrows mitapivat’s potential first-to-market advantage relative to Novo Nordisk’s SCD candidate etavopivat, which Novo has told investors it would advance to a first regulatory filing in the fourth quarter of this year.
Agios has, since January, marketed mitapivat as a treatment for thalassemia, under the name Aqvesme®. Mitapivat is also marketed for hemolytic anemia under the name Pyrukynd®. Both mitapivat drugs combined have generated $65.491 million in net product revenue during the first half of this year, more than triple (209% above) the $21.181 million racked up during January–June 2025.
The company plans to report third quarter results on Thursday.
“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,” Andrew Berens, MD, senior managing director, targeted oncology and a senior research analyst with Leerink Partners, wrote in a research note.
Berens projected in April that mitapivat in SCD had a 60% chance of reaching the market, with peak sales of about $550 million in the United States.
“Interesting period”
“We believe Agios is navigating an interesting period, with the Aqvesme launch in thalassemia underway,” Romero commented. “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.”
Agios said it will continue its labeling discussions with the FDA, including elements of a potential REMS, and will keep working closely with the agency to bring mitapivat to the market as soon as possible.
“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,” Agios CEO Brian Goff said in a statement.
Agios’ sNDA was submitted under the FDA’s accelerated approval pathway, and has been granted Priority Review. The accelerated approval requires a confirmatory clinical trial—a condition Agios is satisfying through the Phase III REIGNITE trial (NCT07656415), which dosed its first patient in July. The trial is designed to demonstrate the clinical benefit of mitapivat on reducing transfusion burden in patients aged 12 years and older with sickle cell disease.
“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,” Goff added. “We will continue to work expeditiously with the goal of bringing mitapivat to patients with sickle cell disease as soon as possible.”