Agios Pharmaceuticals Inc. ( AGIO ) stock plunged on Wednesday after the company released topline results from RISE UP Phase 3 data for mitapivat in sickle cell disease.

AGIO is testing key support levels. See what the experts say here

The trial met its primary endpoint of hemoglobin response, with mitapivat demonstrating a statistically significant improvement compared to placebo.

Also Read: FDA Delays Decision On Agios Pharmaceuticals’ Blood Disorder Drug For Expanded Use

Data

While mitapivat also showed a reduction in the primary endpoint of annualized rate of sickle cell pain crises (SCPCs) compared to placebo, this trend did not achieve statistical significance.

40.6% of patients in the mitapivat arm achieved a hemoglobin response, compared to 2.9% of patients in the placebo arm, a statistically significant improvement.

The annualized rate of SCPCs, defined as acute pain needing medical contact, acute chest syndrome, priapism, hepatic, or splenic sequestration, was 2.62 in the mitapivat arm and 3.05 in the placebo arm.

Mitapivat also demonstrated statistically significant improvements in the first two key secondary endpoints, Week 24 through Week 52 average change from baseline in hemoglobin concentration and levels of indirect bilirubin, a marker of hemolysis, compared with placebo.

The third key secondary endpoint of Week 24 through Week 52 average change from baseline on Patient Reported Outcome Measurement Information System Fatigue 13a (PROMIS Fatigue) score was not met.

The subset of patients in the mitapivat arm who achieved hemoglobin response also experienced clinically meaningful benefits in the endpoints of annualized rate of SCPCs, annualized rate of hospitalizations for SCPCs (the fourth key secondary endpoint of the trial), and PROMIS Fatigue, based on a post hoc analysis.

The safety profile of mitapivat in the RISE UP Phase 3 trial was consistent with that seen in prior mitapivat sickle cell disease trials. 

The average change from baseline in hemoglobin concentration from Week 24 through Week 52 was 7.69 g/L in the mitapivat arm and 0.26 g/L in the placebo arm, a statistically significant improvement.

The average change from baseline in indirect bilirubin from Week 24 through Week 52 was -16.03 µmol/L in the mitapivat arm and 0.88 µmol/L in the placebo arm, a statistically significant improvement.

Elevated levels of indirect bilirubin in the blood can indicate increased hemolysis (red blood cell destruction), which is associated with increased morbidity and mortality in sickle cell disease.

What Next?

Agios intends to submit a marketing application for mitapivat in the U.S. for sickle cell disease after having a pre-supplemental New Drug Application meeting with the U.S. Food and Drug Administration in the first quarter of 2026.

Agios also remains focused on its other near-term commercial and pipeline milestones in 2025 and the first half of 2026 – including the potential U.S. approval of Pyrukynd (mitapivat) for thalassemia, anticipated in early December 2025.

To maximize the Pyrukynd thalassemia U.S. commercial launch and maintain a strong financial position, the company will take proactive steps to reduce operating expenses and provide an update by early 2026.

AGIO Price Action: Agios Pharmaceuticals ( AGIO ) shares were down 49.00% at $23.20 at the time of publication on Wednesday. The stock is trading near its 52-week low of $23.41, according to Benzinga Pro data.

Read Next:

Nvidia CEO Says Anthropic Has ‘Revolutionized’ Agentic AI Space As Jensen Huang, Satya Nadella, Dario Amodei Talk About New Partnership