Bibliographic record
Abstract
To the EditorVoxelotor (Oxbryta, Global Blood Therapeutics (GBT) 440) was developed by GBT for the treatment of sickle cell disease (SCD) in adults and children 12 years of age and older.It exerts its action by binding to the amino acid terminal of both α chains of hemoglobin (Hb).This, in turn, prevents or decreases the polymerization of hemoglobin S (HbS) by increasing Hb oxygen affinity.The efficacy and safety of voxelotor in SCD was evaluated in a phase III randomized, double-blind, placebo-controlled multicenter trial in combination with and without Hounsfield unit (HU) (Heart Outcome Prevention Evaluation Trial (HOPE Trial)) [1].It was approved by the United States Food and Drug Administration on November 19, 2019 [2].The approval was accelerated based on increase in Hb.Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).Efficacy was based on Hb response rate defined as Hb increase of > 1 g/dL from baseline to week 24 in patients treated with voxelotor 1,500 mg versus placebo.The response rate for voxelotor 1,500 mg was 51.1% (46/90) compared to 6.5% (6/92) in the placebo group (P < 0.001).Recommended dosage of voxelotor is 1,500 mg orally once daily with or without food.Recommended dosage for severe hepatic impairment is 1,000 mg orally once daily with or without food [2].From the pharmacokinetic point of view, in vitro and in vivo studies showed that voxelotor is excessively metabolized through phase I metabolism that includes the utilization of cytochrome P450 (CYP450) enzymes (oxidation and reduction), phase II (glucuronidation) and a combination of both phases.Oxidation of voxelotor is mediated mostly by CYP3A4 enzyme with minor contributions from CYP2CI9, CYP2B6 and CYP2C9 [2].This multiplicity of metabolic pathways renders voxelotor vulnerable to drug-drug interactions where other dugs affect its metabolism or, conversely, where voxelotor
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".