Pfizer Presents Promising Phase II/III Results of SCD Treatment Drug GBT601 at ASH 2023

At the American Society of Hematology (ASH) Annual Meeting and Exposition held from December 9th to 12th, 2023, Pfizer showcased the preliminary results of its investigational sickle cell disease (SCD) treatment drug, GBT601. The findings from the Phase II/III study demonstrate that the drug significantly improves hemoglobin levels.

Understanding Sickle Cell Disease (SCD):
SCD is caused by a genetic mutation that results in the production of abnormal β-hemoglobin, a compound rich in iron found in red blood cells (RBCs). This leads to some RBCs assuming a sickle-like shape, becoming sticky and viscous, impairing or obstructing blood flow. Consequently, SCD patients experience anemia and severe pain episodes known as vaso-occlusive events (VOE) or sickle cell crises (VOC).

GBT601: Pfizer's $5.4 Billion Bet:
GBT601 is a next-generation polymerization inhibitor of sickle hemoglobin (HbS). It works by increasing the affinity of HbS for oxygen, preventing the sickling of red blood cells in the bloodstream.

Preliminary Study Results:
The data presented at the ASH conference involved 35 patients, most of whom had completed at least 12 weeks of treatment. Seventeen participants received a 100mg dose of GBT601 as a loading dose twice daily for four days and then once daily. The remaining participants were administered a 150mg dose of GBT601.

After 12 weeks, patients receiving the 100mg dose experienced an average increase in hemoglobin of 2.67g/dL, while those on the 150mg dose saw an average increase of 3.17g/dL. The study also observed a favorable trend in reducing hemolysis markers from baseline.

Researchers noted that GBT601 demonstrated a significant improvement in red blood cell deformability as evidenced by rotational cell counts. Additionally, the median percentage of sickle cells during deoxygenation decreased from baseline at weeks 6 and 12, suggesting a potential delay in sickle hemoglobin polymerization.

The researchers concluded that the efficacy data analysis demonstrated promising evidence of treatment effectiveness, with hemoglobin and oxygen saturation parameters approaching normalization and aligning with the drug's mechanism of action.

In terms of safety, most treatment-related adverse events were of Grade 1 or 2 severity and were largely unrelated to the investigational therapy. Eight patients experienced treatment-related side effects, including diarrhea, abdominal discomfort, and headache. One case of sickle cell anemia crisis was deemed related to GBT021601.

GBT601 as Pfizer's Successor to Oxbryta:
Pfizer positions GBT601 as the successor to Oxbryta, an HbS polymerization inhibitor that received FDA approval for SCD treatment in November 2019. Oxbryta's active ingredient, voxelotor (GBT440), works by increasing hemoglobin's affinity for oxygen, blocking the polymerization of sickle hemoglobin during oxygenation, ameliorating hemolytic anemia and oxygen transport, and potentially altering the course of SCD progression.

GBT601 and Oxbryta were initially developed by California-based Global Blood Therapeutics, which Pfizer acquired for $5.4 billion in August 2022.

In conclusion, the preliminary results of Pfizer's investigational SCD treatment drug, GBT601, presented at ASH 2023, demonstrate its potential to significantly improve hemoglobin levels. This promising data positions GBT601 as a successor to Pfizer's FDA-approved Oxbryta in the treatment of SCD.