Voxelotor May Improve Exercise Capacity In Patients With Sickle Cell Anemia


After 2 months of voxelotor treatment, all patients with sickle cell anemia perceived global improvement, but peak VO2 did not change in 8 of 9 patients.

Since children and adults with sickle cell anemia show decreased cardiopulmonary fitness, a recent study hypothesized that voxelotor would improve exercise capacity in youth with sickle cell anemia.

Led by Vivian Phan, MS, Center for Cancer and Blood Disorders, Pediatric Specialists of Virginia, a team of investigators observed the addition of voxelotor to hydroxyurea led to all patients perceived global improvement, but peak VO2 did not change in most study patients.

The study was presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition.


The study was a single-center, open-label, single-arm longitudinal interventional pilot study for patients with sickle cell anemia aged ≥12 years old. Study participants performed Cardiopulmonary Exercise Testing (CPET#1), took 1500mg voxelotor for 2 months, and then CPET was repeated (CPET#2).

Additionally, investigators performed a modified Bruce Protocol using 2-minute stages on a motorized treadmill, with a goal of 8 -12 minutes of exercise. They collected data on breath by breath gas exchange and analyzed it using a VMax Encore 29C metabolic cart.

The metabolic test consisted of standard monitoring of heart rate, EKG ST changes, arrhythmias, and O2 saturation. They used a respiratory quotient >1.1 as evidence of participant effort.

Each participant had a comparison of peak oxygen consumption (peak Vo2), anaerobic threshold (AT), O2 pulse, VE/VCO2 slope, and time exercise in CPET #1 and CPET#2, with the primary endpoint being peak VO2.

Before CPET#1 and CPET#2, they measured hemoglobin, reticulocyte count, and bilirubin. At the end of the study, the Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.


A total of 9 patients with Hgb sickle cell anemia aged 12 - 20 years completed the study, with 5 females and 4 males. They were stably maintained on hydroxyurea, continued without dose changes during the study period.

Following 2 months of voxelotor treatment, all patients demonstrated the expected hematologic changes, including mean rise in Hgb (+1.3 g/dL; 95% CI, 0.8 - 1.7), mean decrease in reticulocyte count (-2.4%; 95% CI, -4.1 to -0.8), and mean decrease in bilirubin (-0.4 mg/dL; 95% CI, -0.8 to -0.1).

Data show oxygen consumption, as percent predicted peak VO2, ranged from 52% to 80% in CPET #1 and from 55% to 71% in CPET #2.

Changes in peak VO2 for individual participants ranged from -10% to +10% of predicted peak VO2, with a mean difference of -2.2% (95% CI, -7.1 - 2.7) which is insignificant (P = .3).

When using +/- 6% as variability in peak VO2 measurement, a total of 5 participants exhibited no change, 3 participants had a decrease in peak Vo2 of -7%, -9%, -10%. A single patient experienced an increase of +10%, who exercised alone following voxelotor.

They found no significant changes in anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised, as well as no correlation with changes in peak V02. All achieved respiratory quotient >1.1, which assured participant effort during CPET.

Data from the 7-point PGIC questionnaire evaluated activity limitations, symptoms, emotions, and overall quality of life. Of the 9 participants, 7 reported positive change, which included “a great deal better,” “definite,” and “moderate” improvement. No patient reported worsening.

On the other hand, the clinicians reported “minimal” to “much” improvement on CGIC for all 9 participants.


Overall, Phan and colleagues noted that the study helped to demonstrate the feasibility of CPET in evaluating exercise capacity longitudinally in youth with sickle cell anemia.

“To increase peak VO2, higher Hgb increase, concurrent regular exercise, and longer exposure to voxelotor may be necessary,” investigators wrote.

The study, “The Effect of Voxelotor on Exercise Capacity of Youths with Sickle Cell Anemia,” was published online by ASH.

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