Case series of patients with severe sickle cell disease treated with voxelotor (GBT440) by compassionate access

Blyden, Gershwin T.; Bridges, Kenneth R.; Bronte, Lanetta

doi:10.1002/ajh.25139

Cited by 22 publications

(20 citation statements)

References 5 publications

(6 reference statements)

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“…The same case series also reported that in those severe sickle cell disease patients (Hb<6 g/dL), voxelotor therapy improved Hb levels and oxygen saturation, and also reduced the need for hospital admission for episodes of vaso-occlusive crisis pain in the first 24 weeks of therapy [14]. A pivotal phase 3 trial known as GBT-HOPE (NCT03036813) was carried with voxelotor as test drug to assess its safety and efficacy compared to placebo in sickle cell disease patients [5].…”

Section: Clinical Trials On Voxelotormentioning

confidence: 78%

“…Moreover, another case series reported by Blyden and his colleagues documented the compassionate use of voxelotor in seven patients suffering from severe sickle cell disease [14]. The treatment options for severe sickle cell disease are rather limited mainly because of the lack of US FDA approved drugs and therapies and also because of systematic exclusion of such patients from ongoing trials for investigational drugs.…”

Section: Clinical Trials On Voxelotormentioning

confidence: 99%

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Voxelotor: A Ray of Hope for Sickle Disease

AlDallal¹

2020

Cureus

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Sickle cell disease is one challenging blood disorder, affecting around 100,000 people in the United States alone. None of the currently approved drugs can modify the underlying pathology of the disease. Voxelotor, first of its kind, is an orally administered drug that can alter the underlying disease pathology (by increasing the affinity between Hb and oxygen) and inhibit sickling of red blood cells. Several clinical trials and case series have documented the benefits and safety of voxelotor therapy in sickle cell disease. Currently, the US FDA has approved the drug for treatment of sickle cell disease and also granted the status of orphan drug.

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Section: Clinical Trials On Voxelotormentioning

confidence: 78%

Section: Clinical Trials On Voxelotormentioning

confidence: 99%

Voxelotor: A Ray of Hope for Sickle Disease

AlDallal¹

2020

Cureus

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“…In addition to the two clinical trials evaluated above, there were three case series or reports demonstrating voxelotor use in patients with SCD. The first case series presented seven patients with HbSS or Sβ 0 who were treated with voxelotor by compassionate‐use access 19 . The treatment dose was 900 mg once daily with a possible escalation to 1500 mg daily, and the therapy lasted from 6 to 17 months.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Voxelotor: A First‐in‐Class Sickle Hemoglobin Polymerization Inhibitor for Management of Sickle Cell Disease

Han

Saraf

2020

Pharmacotherapy

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Voxelotor, a sickle hemoglobin polymerization inhibitor, was approved by the U.S. Food and Drug Administration to treat sickle cell disease (SCD) in November 2019. This article reviews published data about voxelotor treatment of SCD based on a search of MEDLINE, Embase, and International Pharmaceutical Abstracts. In a phase I/II trial, voxelotor demonstrated a dose‐dependent pharmacokinetic and pharmacodynamic response and was well tolerated in healthy volunteers and patients with SCD. In a multi‐center, randomized, double‐blind, phase III trial (HOPE trial), a significantly higher percentage of patients randomized to voxelotor had increased hemoglobin (> 1 g/dl from baseline) compared to placebo. A greater reduction of hemolytic markers was also observed in the voxelotor‐treated group, whereas the incidence of adverse effects was comparable. Three case series or reports also demonstrated the efficacy and safety of voxelotor use in a limited number of SCD patients in the real‐world situation, although one patient with SCD, severe anemia, and a history of autoantibody‐mediated hemolysis failed to respond to voxelotor. An ongoing trial (HOPE‐KIDS) is designed to establish the use of voxelotor in younger pediatric patients with SCD. There is a theoretical concern that voxelotor may impair oxygen delivery, due to modification of the oxygen affinity of hemoglobin, which needs to be further evaluated. As a first‐in‐class hemoglobin modulator, voxelotor offers a new treatment option targeting the root cause of SCD.

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“…However, hemoglobin occupancy failed to reach the 25%-30% percent modification required to be therapeutic in sickle cell patients with less severe anemia. 9 When compared with other severe SCD patients treated on a compassionate basis with Voxelotor, 7 it is possible that autoantibody mediated hemolysis shortened an already reduced red cell half-life in our patient. As a result, rapid red cell clearance would negatively impact drug pharmacokinetics and account for the low Voxelotor occupancy in our patient although her hemolysis parameters do not overwhelmingly favor this hypothesis (Table 1).…”

Section: Occupancy Of Hemoglobin By Voxelotor and Formation Of Anmentioning

confidence: 86%

“…6 Given the lack of success in treating this patient, we attempted a compassionate basis therapeutic trial of Voxelotor using an FDA approved eIND application. 7 The patient began Voxelotor 1500 mg/day and experienced relatively minor side effects (headache and grade II diarrhea) while being adherent to the treatment (determined by pill counts and observation of a split HemoglobinS peak on cation exchange high-performance liquid chromatography). 8 The predicted percent modification of hemoglobin at this dosage is 25%-30% (Supporting Information, Figure S2B).…”

Section: Occupancy Of Hemoglobin By Voxelotor and Formation Of Anmentioning

confidence: 99%