Voxelotor Results in Hematologic Improvements for Sickle Cell Disease

Kathryn Muschick, Prisma Health

New research continues to show the value in voxelotor as a treatment for patients with sickle cell disease (SCD).

A team, led by Kathryn Muschick, Prisma Health, quantify the hematologic response and validated reported outcomes with voxelotor treatment for patients with sickle cell disease.

The Treatment

Voxelotor is a once-daily oral medication that inhibits HbS polymerization.

“It has the potential to be a chronic, preventative, disease-modifying treatment for SCD,” the authors wrote. “Anemia is a prominent characteristic of SCD, and Hb level is a clinically relevant and objective measure of disease severity in SCD.”

In the study, the investigators used real-world data collected retrospectively from patients with sickle cell disease between 12-70 years who were treated with standard-of-care procedures.

The data was collected both before and during voxelotor treatment.

Patient Demographics

The retrospective, investigator-initiated, single-center chart review study included 77 patients with a mean age of 30.4 years, but 30% of patients were younger than 21 years. In addition, 62% of patients were female, 86% had a homozygous hemoglobin S (HbSS) genotype, and 82% were treated with concomitant hydroxyurea.

In addition, the mean baseline Hb level was 8.3 g/dL, reticulocyte percentage was 11.5%, and the total bilirubin was 3.5 mg/dL. Also, the mean duration of voxelotor treatment was 9.7 months (range, 1.9-17 months).

Some of the favorable responses to voxelotor treatment and signs of hematologic response after voxelotor treatment included increased Hb levels, decreased reticulocyte percentage, and decreased total bilirubin.

Patients treated with concomitant hydroxyurea had a more robust improvement compared to voxelotor alone. This suggest a complementary effect.

“Hematologic improvements were observed after voxelotor treatment, with a potential additive benefit with concomitant HU treatment,” the authors wrote.

Safety

For safety, 4 patients suffered from adverse events that resulted in dose modification. Of this group, 2 adult patients had episodes of diarrhea and 1 adult patient had a rash that was potentially related to the treatment.

There was also 1 pediatric patient with a fever that was deemed unrelated to the treatment.

In addition, all of the adverse events were resolved following dose modification.

The Need

One of the main reasons for the attention to voxelotor is the slow evolution of sickle cell disease treatments.

“Curative-intent therapies, such as allogeneic stem cell transplantation and gene therapy, offer hope for the future but still carry high risks of treatment-related side effects that limit uptake within the patient population,” the authors wrote. “Over the past 30 years, disease modification with HU has become the standard-of-care treatment for individuals with more severe SCD genotypes and HU treatment has been shown to decrease certain short-term and long-term disease complications.”

However, serious disease-related complications continue to be an issue for patients, leading to poor quantity and quality of life.

The study, “Real‐World Data On Voxelotor To Treat Patients With Sickle Cell Disease,” was published online in the European Journal of Haematology.