ASH23: Pfizer's next-gen sickle-cell therapy shows early promise
10 Dec 2023
Clinical ResultGene TherapyAcquisitionASHPhase 1
Preliminary data from an ongoing Phase II/III trial of Pfizer's HbS polymerisation inhibitor GBT601 showed increased haemoglobin (Hb) and improvements in red blood cell (RBC) deformability through to 12 weeks. Pfizer got its hands on the treatment, a next-generation version of Oxbryta (voxelotor), through its acquisition of Global Blood Therapeutics for $5.4 billion late last year.
The results, presented over the weekend at the American Society of Hematology (ASH) annual meeting, are derived from Part A of the dose-finding portion of the trial. Eligible patients were randomly assigned to GBT601 100mg or 150mg, with the primary endpoint being change from baseline in Hb at week 12. As of the June 20 cut-off date, 28 of the 35 patients who had received treatment in Part A completed 12 weeks of treatment.
'Robust improvements' on RBC measures
Researchers said GBT601 was associated with "robust improvements" in several RBC parameters at 6 and 12 weeks. According to the ASH presentation, the mean Hb increase from baseline was 2.67 g/dL for the 100mg group and 3.17 g/dL for the 150mg group. There were also increases in haematocrit of close to 7.9% in the 100mg arm and just over 9.6% in the 150mg arm, while RBC counts rose 1.32 1012/L and 1.53 1012/L in the two groups, respectively, "thus approaching the normal range for these RBC parameters," the study authors said.
Investigators noted that ektacytometry results with GBT601 also showed "marked improvement in RBC deformability." In addition, they reported that the median point of sickling during deoxygenation decreased from baseline at weeks 6 and 12 with GBT601, indicating that polymerisation of sickle Hb was likely delayed.
"Analyses of [pharmacodynamic] data show promising evidence of efficacy with near normalisation of Hb and oxygenscan parameters consistent with the improved mechanism of the drug," researchers concluded.
The readout follows the FDA approvals late last week of two sickle-cell gene therapies, including first CRISPR medicine. The US regulator cleared Vertex Pharmaceuticals and CRISPR Therapeutics' Casgevy (exagamglogene autotemcel), which uses CRISPR/Cas9 gene-editing technology, as well as bluebird bio's Lyfgenia (lovotibeglogene autotemcel) as the first cell-based gene therapies for the treatment of sickle-cell disease in patients 12 years and older.
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