Agios Pharmaceuticals announced that it will seek U.S. accelerated approval for its oral pyruvate kinase activator, mitapivat, in sickle cell disease. The company’s pre‑supplemental New Drug Application (sNDA) meeting with the FDA confirmed that the agency recommended a proposal for a confirmatory clinical trial to support accelerated approval.
The RISE UP Phase 3 program, which underpinned the accelerated‑approval request, demonstrated a statistically significant hemoglobin response in patients but did not meet the primary pain‑crisis endpoint. Post‑hoc analyses of the trial data revealed that patients who achieved the hemoglobin response experienced clinically meaningful reductions in pain crises and fatigue, a nuance that likely influenced the FDA’s willingness to consider accelerated approval.
On the day of the announcement, Agios shares rose between 12 % and 20 %. Investors cited the FDA’s recommendation for a confirmatory trial, the potential for mitapivat to become the first oral therapy for sickle cell disease, and the company’s strong track record with existing mitapivat indications as key drivers of the positive market reaction.
Agios has shown robust revenue growth from its existing mitapivat products. In Q4 2025, U.S. net revenue for PYRUKYND rose 49 % year‑over‑year to $16.0 million, and full‑year 2025 PYRUKYND revenue reached $54.0 million. The company reported a net loss of $108.0 million for Q4 2025 but maintained a strong cash position of $1.2 billion as of December 31 2025, providing financial flexibility to support the accelerated‑approval effort. Operating expenses are expected to remain approximately flat compared to 2025, reflecting disciplined cost management amid ongoing clinical development.
Chief Medical Officer Sarah Gheuens said, “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.” Chief Executive Officer Brian Goff added, “In 2026, we are focused on driving a high‑impact U.S. launch of AQVESME, expanding our PK activation franchise into additional high‑value indications such as sickle cell disease, and advancing our promising early‑stage pipeline.”
The accelerated‑approval pathway could position mitapivat as the first oral therapy for sickle cell disease, potentially capturing a sizable patient population and diversifying Agios’s product portfolio beyond its current rare‑anemia indications. The move also signals the company’s intent to capitalize on an unmet need while navigating the FDA’s accelerated‑approval pathway.
The confirmatory trial that will support the accelerated approval will use a different primary endpoint than the RISE UP trial, a change informed by the RISE UP data and FDA discussions. This adjustment reflects the FDA’s focus on demonstrating a clear clinical benefit beyond hemoglobin improvement, such as reduction in pain crises or other patient‑reported outcomes.
Sickle cell disease treatment options include crizanlizumab and voxelotor, both of which have faced market withdrawals or limited uptake. Mitapivat’s oral formulation could differentiate it from existing therapies that require injections or infusions, offering a more convenient and potentially cost‑effective option for patients and payers.
The pursuit of accelerated approval for mitapivat represents a significant regulatory milestone for Agios and a strategic expansion into a high‑need therapeutic area, underscoring the company’s commitment to advancing its PK‑activation platform across multiple rare‑anemia indications.
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