Pfizer's $5.4B Bet Pays Off: GBT601 Shows Promising Phase II Data in Sickle Cell Disease
Pfizer
Pharmaceutical R&D Developer
At the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition held from December 9-12, Pfizer presented preliminary Phase II/III study results of its investigational sickle cell disease (SCD) treatment drug GBT601. The study results showed that the drug significantly increased hemoglobin levels.
SCD is caused by a mutation in the gene that produces β-hemoglobin, an iron-rich compound present in red blood cells (RBCs). This results in some red blood cells taking on a "sickle" shape, becoming sticky, slowing or obstructing blood flow, and leading to anemia and severe pain, known as vaso-occlusive episodes (VOE) or vaso-occlusive crises (VOC).
GBT601 Lives Up to Pfizer's $5.4 Billion Bet
GBT601 is a new generation polymerization inhibitor of sickle hemoglobin (HbS). It prevents the sickling of red blood cells in the blood by increasing the affinity of HbS for oxygen.
The data presented at the ASH conference came from 35 patients, most of whom had completed at least 12 weeks of treatment. Seventeen subjects received a 100mg dose of GBT601, with a twice-daily loading dose for four days, followed by once-daily dosing. The remaining subjects were administered 150mg of GBT601.
After 12 weeks, the hemoglobin levels of subjects receiving the 100mg dose increased by an average of 2.67 g/dL, while patients receiving the 150mg dose experienced an average hemoglobin increase of 3.17 g/dL. Researchers also observed a favorable trend in the reduction of hemolysis markers from baseline.
The researchers noted that the rotational cell count results of GBT601 also showed "a significant improvement in red blood cell deformability." In addition, they reported that when using GBT601, the median point of sickle cells during deoxygenation decreased from baseline at weeks 6 and 12, indicating that the polymerization of sickle Hb may be delayed.
The researchers concluded: "The pharmacodynamic data analysis shows promising evidence of efficacy, with hemoglobin and oxygen scan parameters approaching normalization, consistent with the improved mechanism of the drug."
In terms of safety, the severity of most treatment-induced adverse events was Grade 1 and Grade 2, and most were considered unrelated to the study treatment. A total of 8 patients experienced treatment-related side effects, including diarrhea, abdominal discomfort, and headache. One case of sickle cell anemia crisis was determined to be related to GBT021601.
Pfizer positions GBT601 as the successor to its Oxbryta, an HbS polymerization inhibitor that received FDA approval in November 2019 for SCD.
The active ingredient in Oxbryta is voxelotor (GBT440), which improves hemolytic anemia and oxygen transport by increasing hemoglobin's affinity for oxygen, blocking the polymerization of oxygenated sickle hemoglobin and red blood cell sickling, potentially altering the course of SCD development.
GBT601 and Oxbryta were initially developed by Global Blood Therapeutics, a company headquartered in California, which Pfizer acquired for $5.4 billion in August 2022.
SCD Drugs Blossom Across the Board
Before Pfizer disclosed the preliminary results of GBT601's Phase II/III study, the SCD field had received two landmark approvals.
On December 8, the FDA approved Casgevy (exagamglogene autotemcel), a gene-editing therapy jointly developed by Vertex Pharmaceuticals and CRISPR Therapeutics. On the same day, Lyfgenia (lovotibeglogene autotemcel), a therapy from the veteran gene therapy developer Bluebird Bio, was also approved by the FDA.
The indications for the two drugs are exactly the same: for the treatment of sickle cell disease (SCD) patients aged 12 years and older with recurrent vaso-occlusive crises (VOC), placing them in direct head-to-head competition.
However, there is a huge difference in price between the two.
According to public information, Bluebird Bio's Lyfgenia gene therapy is currently priced at $3.1 million, while the competitor's Casgevy gene-editing therapy is currently priced at $2.2 million.
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Editorial Responsibility: Pea Shooter
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