Most Read Articles
Roshini Claire Anthony, 2 days ago

Patients undergoing chemotherapy for breast or haematological cancers could potentially reduce their risk of chemotherapy-related cardiotoxicity with the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), or beta-blockers as primary prevention, according to a systematic review and meta-analysis presented at the recent EuroEcho 2019 conference.

Tristan Manalac, 4 days ago
Users of electronic nicotine delivery systems are likely to have received a diagnosis of clinical depression in the past, according to a recent study.
Pearl Toh, 06 Dec 2019
Getting just under one extra hour of sleep per night can go a long way for the health of college students, who are often sleep-deprived, a study suggests.
Jairia Dela Cruz, Yesterday
Use of isatuximab (Isa) in combination with pomalidomide and dexamethasone (PomDex) appears to lead to more favourable outcomes in elderly patients with relapsed/refractory multiple myeloma (RRMM) as compared with PomDex alone, according to the results of a subgroup analysis of the ICARIA-MM trial presented at the 61st Annual Meeting of the American Society of Hematology (ASH 2019).

Voxelotor increases Hb levels, reduces haemolysis in sickle cell disease

Elaine Soliven
18 Jul 2019

Treatment with voxelotor, an HbS* polymerization inhibitor, significantly increases haemoglobin (Hb) levels and reduces markers of haemolysis, including indirect bilirubin level and percentage of reticulocytes, compared with placebo in patients with sickle cell disease, according to the HOPE** trial.

“The [significant] increase in Hb levels and reduction in haemolysis occurred within 2 weeks after initiation of the trial drug, indicating a rapid pharmacodynamic and biologic effect,” said the researchers.

This phase III, multicentre, international, double-blind trial involved 274 adolescents (aged 12–17 years) and adults (aged 18–65 years) with sickle cell disease who were randomized in a 1:1:1 ratio to receive oral voxelotor at a dose of 1,500 mg (n=90, median age 24 years) or 900 mg (n=92, median age 24 years) or placebo (n=92, median age 28 years) once daily for 24 weeks. The primary endpoint was the percentage of patients who achieved an Hb response (defined as an increase in Hb level of >1.0 g/dL at 24 weeks from baseline). [N Engl J Med 2019;doi:10.1056/NEJMoa1903212]

In the intention-to-treat analysis, significantly more patients who received voxelotor 1,500 mg achieved a >1.0 g/dL increase in Hb levels compared with placebo at 24 weeks (51.0 percent vs 7.0 percent; p<0.001), irrespective of concurrent use of hydroxyurea or anaemia severity at baseline, said the researchers.

A higher percentage of patients on voxelotor 900 mg also achieved an increased Hb level than those on placebo at 24 weeks (33.0 percent vs 7.0 percent).

At 24 weeks of follow-up, patients treated with voxelotor 1,500 mg had a significantly greater reduction in the indirect bilirubin level (mean change from baseline, -29.1 percent vs -3.2 percent; p<0.001) and percentage of reticulocytes (mean change from baseline, -19.9 percent vs 4.5 percent; p<0.001) than those who received placebo.

The 900 mg voxelotor group also saw reductions in indirect bilirubin level (-20.3 percent vs -3.2 percent) and percentage of reticulocytes (-1.3 percent vs 4.5 percent) vs placebo.

With regards to the incidence rate of vaso-occlusive crisis, there was a trend towards fewer incidence of the total number of vaso-occlusive crises for both doses of voxelotor compared with placebo (179 [for 1,500 mg] and 183 [for 900 mg] vs 219).

“The absence of an increased incidence rate of vaso-occlusive crisis with voxelotor despite significant increases in the Hb level suggests that voxelotor raises Hb levels without negatively affecting blood viscosity,” said the researchers. “This may be due to the upstream mechanism of action of voxelotor (inhibition of HbS polymerization), which results in improved red-cell deformability and reduced blood viscosity with voxelotor in vitro.” [Clin Hemorheol Microcirc 2018;70:95-105]

Adverse events (AEs) of any grade were comparable between the treatment groups (94 percent and 93 percent vs 89 percent for voxelotor 1,500 and 900 mg vs placebo, respectively). The researchers reported that most AEs were not related to the trial drug, voxelotor, or placebo.

“We specifically chose to use an increase in Hb level of >1.0 g/dL as a primary endpoint because validated natural history studies indicated that an increase in Hb level significantly decreases the rate of multiorgan failure and death,” said the researchers.

“[Furthermore,] the Hb response and reduction in haemolysis observed with an orally administered, once-daily medication with side effects that minimally affect lifestyle may make voxelotor a promising advancement in the management of sickle cell disease if approved by the FDA***,” wrote Dr Alexis Thompson from the Northwestern University Feinberg School of Medicine, Chicago, US, in an editorial. [N Engl J Med 2019;doi:10.1056/NEJMe1906771]

“Long-term follow-up studies are planned to evaluate the effect of the increase in Hb level and decrease in haemolysis induced by voxelotor on morbidity and mortality among persons with sickle cell disease,” the researchers noted.

 

*HbS: Sickle haemoglobin
**HOPE: Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization

***FDA: Food and Drug Administration
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Doctor - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
Roshini Claire Anthony, 2 days ago

Patients undergoing chemotherapy for breast or haematological cancers could potentially reduce their risk of chemotherapy-related cardiotoxicity with the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), or beta-blockers as primary prevention, according to a systematic review and meta-analysis presented at the recent EuroEcho 2019 conference.

Tristan Manalac, 4 days ago
Users of electronic nicotine delivery systems are likely to have received a diagnosis of clinical depression in the past, according to a recent study.
Pearl Toh, 06 Dec 2019
Getting just under one extra hour of sleep per night can go a long way for the health of college students, who are often sleep-deprived, a study suggests.
Jairia Dela Cruz, Yesterday
Use of isatuximab (Isa) in combination with pomalidomide and dexamethasone (PomDex) appears to lead to more favourable outcomes in elderly patients with relapsed/refractory multiple myeloma (RRMM) as compared with PomDex alone, according to the results of a subgroup analysis of the ICARIA-MM trial presented at the 61st Annual Meeting of the American Society of Hematology (ASH 2019).