Real-World Experience of Patients with Sickle Cell Disease Treated with Voxelotor: A Single Centre Experience at University College Hospital in London

Introduction

Voxelotor, recently approved by NICE, is indicated for the treatment of haemolytic anaemia due to sickle cell disease (SCD) in adults and paediatric patients aged over 12 as monotherapy or in combination with hydroxycarbamide. Rather than addressing symptoms directly, the goal of Oxbryta® therapy - by targeting HbS polymerisation - is to interrupt the pathophysiological cascade, starting at the molecular basis of sickle cell disease. In England, around 17,000 people are living with sickle cell disease with 250 new cases a year. The pivotal phase 3 clinical trial HOPE, showed that more than half (51%) of people given Voxelotor had an increase in haemoglobin which could improve symptoms and quality of life. We need more prospective real-world experience to understand this drug's impact on the clinical phenotype of the disease and quality of life.

Methods

Seven patients have been initiated on Voxelotor since January 2022, all of African and AfricanCaribbean ancestory. Five of them are females and the mean age is 48 years. Six patients have homozygous SCD (HbSS), and one has the HbS/β⁺-thalassaemia genotype. The indication for commencing Voxelotor in three of the patients, was history of delayed haemolytic transfusion reaction, hyperhaemolysis and the presence of alloantibodies, rendering them therefore very difficult to transfuse. Two patients had a significant haemolytic phenotype and/or prolonged haemolysis-related complications such as recurrent leg ulcers. Three patients were also on hydroxycarbamide (HU) alongside Voxelotor, two had previously taken HU but discontinued before starting Voxelotor, and two more had denied ever commencing HU. Voxelotor was initiated at 1500 mg in six patients and 500 mg in one patient which was later also increased to 1500 mg.

Results

The average time of follow-up on Voxelotor treatment was 13 months. Haemoglobin response (> 10 g/L, as per HOPE Phase 3 trial primary objective), was observed in four patients, when comparing the baseline steady state with the most recent haemoglobin levels (average increase 24 g/L). Three of the patients did not respond, however, one of them discontinued for a few months due to drug shortage. None out of the four responders has been transfused since Voxeletor was started. Haemolytic markers (reticulocyte count, total bilirubin, lactate dehydrogenase) were not consistently monitored in all patients throughout the follow-up period, however, two patients with frequent monitoring had a pronounced decrease in all markers. Five patients had clinical improvement in addition to haematological and biochemical response: three reported less fatigue, one mentioned less frequent SCD-associated vaso-occlusive crises and one has reported healed ulcers that have not recurred since the initiation of Voxelotor. Four patients have not reported any side effects and three experienced mild side effects such as headache, fatigue and short-lasting, self-resolved bone pain after taking the daily dose of Voxelotor; the latter was managed by reducing the dose to 1000 mg.

Conclusion

From our experience in our centre, the majority of the patients responded with an increment of the haemoglobin and reduction of haemolytic markers, in keeping with the reported outcomes of the HOPE Phase 3 clinical trial but in addition we observed a positive clinical response. Consistent monitoring of haemolytic markers will provide necessary insight into Voxelotor's efficiency. More monitoring and experience with the Voxelotor are warranted to understand the impact this drug will have on morbidity and patient experience.

No relevant conflicts of interest to declare.