Voxelotor Can Promote Long-Term Benefits in Teens, Adults with SCD, Latest Clinical Data Show

Alice Melão avatar

by Alice Melão |

Share this article:

Share article via email
CTX001 Phase 1/2 trial

Global Blood Therapeutics’ lead therapeutic candidate voxelotor can induce rapid, robust, and sustained improvements in the amount of hemoglobin in adolescents and adults with sickle cell disease (SCD), according to interim results from the first part of a Phase 3 trial.

The latest results of GBT’s clinical program for voxelotor were recently presented at the 60th American Society of Hematology Annual Meeting & Exposition in San Diego.

Findings from the ongoing Phase 3 HOPE trial (NCT03036813) were revealed in a presentation titled “Results from Part A of the Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization (HOPE) Trial (GBT440-031) at 24-weeks, a Placebo-Controlled Randomized Study Evaluating Voxelotor (GBT440) in Adults and Adolescents with Sickle Cell Disease.”

The two-part study is designed to evaluate the effectiveness and safety of voxelotor in sickle cell patients ages 12 to 65.

In part A, researchers compared the effects of 900 or 1,500 mg per day of voxelotor or a placebo in 154 patients treated for 24 weeks. Part B of the trial originally planned to enroll 250 patients who would be randomized to receive either a placebo or a dose of voxelotor selected from the first part.

Results from the first part showed that 65% of patients taking the 1,500 mg dose and 33% taking the 900 mg dose had an increase in hemoglobin levels greater than 1 g/dL at 24 weeks, compared with only 10% of patients on the placebo. This positive effect was reported as early as the first two weeks and was sustained through the 24 weeks of treatment.

The highest tested dose increased hemoglobin levels from an initial mean value of 8.6 g/dL to 10 g/dL at 24 weeks, which is consistent with a clinically meaningful improvement in anemia.

The therapeutic activity of voxelotor was not influenced by other ongoing therapies, demonstrated by the fact that 64% of patients enrolled in part A were on background use of hydroxyurea throughout the trial.

Both doses tested also led to significant improvements in the levels of reticulocytes (immature red blood cells) and bilirubin — two biomarkers of healthy blood cells — further demonstrating the effectiveness of voxelotor in treating sickle cell disease.

Voxelotor-treated patients experienced fewer acute vaso-occlusive crises — a painful and potentially severe complication of SCD — than the placebo group.

“These longer-term efficacy and safety data from more than 150 patients enrolled in the HOPE Study continue to support the potential of voxelotor to be a disease-modifying treatment for SCD,” Elliott Vichinsky, MD, lead investigator of the HOPE study, said in a press release.

In general, the treatment was safe and well-tolerated by the patients, with similar safety profiles between the two tested doses.

GBT is also currently evaluating voxelotor in sickle cell patients ages 4 to 17 in the Phase 2a HOPE-KIDS 1 trial (NCT02850406).

Interim results from part B of the trial were discussed at the San Diego meeting in the presentation, “Efficacy and Safety of 1500mg Voxelotor in a Phase 2a Study (GBT440-007) in Adolescents with Sickle Cell Disease.”

In part A, researchers evaluated the safety and efficacy of a single 600 mg dose of voxelotor in 13 patients ages 6 to 17. Part B was designed to explore voxelotor at daily doses of 900 and 1,500 mg in 36 patients ages 12 to 17 for 24 weeks.

In part C, which is currently recruiting participants, researchers will assess the effects of a single 1,500 mg dose (or weight-based equivalent) in up to 50 patients ages 4 to 17 for up to 48 weeks.

Data collected from 11 patients treated with 1,500 mg of voxelotor showed a significant increase in hemoglobin levels at 16 weeks. These patients also showed improvements in the levels of reticulocytes and bilirubin.

Six of these patients achieved an increase in hemoglobin levels greater than 1 g/dL at 16 weeks, with a median hemoglobin change of 1.1 g/dL over initial values.

The safety and tolerability profile of voxelotor in this Phase 2a trial was similar to that reported during the Phase 3 HOPE trial.

GBT is planning to present the results from part C of the HOPE-KIDS 1 trial at a future medical meeting.

“These major improvements in anemia and hemolysis have the potential to prevent the chronic organ damage that is the leading cause of death in patients with SCD in the United States,” said Vichinsky, who is the director of hematology/oncology at UCSF Benioff Children’s Hospital in Oakland, California. “In addition to the large improvements in hemolytic anemia, I am greatly encouraged in seeing a very good safety profile.”

Voxelotor, formerly known as GBT440, is designed to be an oral, once-daily therapy for SCD. It is intended to increase hemoglobins’ affinity for oxygen, which, when bound, will prevent the aggregation of hemoglobins and the resulting sickling of red blood cells.

The FDA granted the treatment breakthrough therapy designation in January, in addition to the previously granted fast track, orphan drug, and rare pediatric disease designations for its potential as a sickle cell treatment. The European Medicines Agency also included volexotor in its Priority Medicines (PRIME) program.

These designations are granted to therapies that have demonstrated promising results to treat rare diseases, and provide support for faster development and review for approval.

GBT is planning to submit a new drug application (NDA) for voxelotor under the FDA’s accelerated approval program in 2019.

“These data from the Phase 3 HOPE Study, including the clinically meaningful and statistically significant increase in hemoglobin, have been a key element in the discussions with the FDA,” said Ted W. Love, MD, president and CEO of GBT. “To further support our NDA submission, we are continuing to generate efficacy and safety data on an additional 118 patients in the HOPE Study.”