Long-term voxelotor use increases Hb, reduces haemolysis markers in patients with SCD

Long-term treatment with voxelotor 1,500 mg led to sustained improvements in haemoglobin (Hb) levels and reductions in clinical markers of haemolysis among patients with sickle cell disease (SCD), according to an updated interim analysis of the HOPE open-label extension (OLE) study presented at ASH 2023.

“Voxelotor is a first-in-class haemoglobin S polymerization inhibitor that has been approved for the treatment of patients with SCD [for those aged ≥4 years in the US and UAE and aged ≥12 years in Oman, Kuwait, and Saudi Arabia,] as well as haemolytic anaemia with SCD [for those aged ≥12 years in the EU and Great Britain],” said Dr Maureen Achebe from Brigham and Women’s Hospital, Harvard Medical School in Boston, Massachusetts, US.

This ongoing OLE study analysed 178 patients (median age 25 years, 56.2 percent female) with SCD who completed 72 weeks of treatment with voxelotor 1,500 or 900 mg or placebo in the HOPE trial to assess the long-term effects of voxelotor.

In the current study, all placebo recipients were switched to voxelotor 1,500 mg once daily (previously placebo-treated group) and those on voxelotor 1,500 mg previously continued treatment (previously voxelotor-treated group) through week 168. [ASH 2023, abstract 2527]

From week 24 (OLE baseline) to week 168, mean Hb levels improved and were sustained for both patients who previously received placebo and switched to voxelotor (from 0.9 to 1.1 g/dL) and for those who continued to receive voxelotor (from 0.2 to 0.5 g/dL).

By week 168, both previously placebo- and voxelotor-treated groups also demonstrated reductions in haemolysis markers, including indirect bilirubin (mean change from OLE baseline, -16.5 percent and -15.7 percent, respectively) and reticulocyte percentage (mean change from OLE baseline, -44.8 percent and -44.0 percent).

Of note, this indicated that patients treated with voxelotor for a combined ≥240 weeks (4.6 years) showed durable responses in Hb and clinical markers of haemolysis in both the HOPE and HOPE OLE studies, said the researchers.

Furthermore, the HOPE OLE population had a low annualized incidence rate of vaso-occlusive crisis, reported as sickle cell anaemia with crisis or acute chest syndrome, with 1.1 events occurring per year.

In terms of safety, 88.2 percent of patients reported non-SCD-related treatment-emergent adverse events (TEAEs), such as arthralgia (17.4 percent), headache (17.4 percent), and pain in the extremities (15.7 percent) in both groups.

Eight deaths due to fatal TEAEs were reported, but none of these incidents “were considered by the investigators to be related to the study drug,” said the researchers.

“The safety profile was identical to that of the original HOPE trial … with no new safety signals identified after exposure for 168 weeks in the OLE and a combined 240 weeks across both studies,” noted Achebe.

“Overall, long-term use of voxelotor 1,500 mg was well tolerated and effective at maintaining improvement in anaemia [(increased Hb levels)] and reductions in haemolysis [(decreased indirect bilirubin and percentage of reticulocytes)] in patients with SCD,” Achebe concluded.