Global Blood Therapeutics (GBT) has a shot at launching the first disease-modifying drug for sickle cell disease (SCD), a life-threatening genetic disorder affecting more than 100,000 Americans. The company reported strong interim results for its drug voxelotor back in December, but updated results in more patients left investors wondering if voxelotor's efficacy will translate into meaningfully better outcomes.
What's sickle cell disease?
A genetic disorder, a mutation to the HBB gene makes it so that SCD patients can't produce normal hemoglobin, a red blood cell protein responsible for transporting oxygen to organs through the blood.
Typically, red blood cells are flexible and last approximately 120 days. In SCD patients, the mutation causes stiff fibers in hemoglobin that result in red blood cells that are fragile and last only 10 to 20 days. The disease is named after the sickle, or crescent shape, of the abnormal red blood cells formed because of the genetic mutation.
Because of the shortened life cycle of red blood cells, SCD patients are at risk of severe anemia that can damage organs over time. Furthermore, because the sickle-shaped red blood cells are less flexible, they can cause obstructions that result in painful and dangerous vaso-occlusive crisis, often resulting in hospitalization.
Although spending can run into the hundreds of thousands of dollars annually, the toll taken on SCD patients results in a shortened life span, indicating that significantly better treatment options are necessary.
A different treatment approach
An oral, once-daily drug, voxelotor attempts to reduce anemia and red blood cell sickling and death by increasing hemoglobin's affinity for oxygen. By increasing oxygen in hemoglobin, it aims to keep it flexible, thereby reducing the formation of sickled red blood cells.
Improving hemoglobin production is particularly significant because low hemoglobin levels can contribute to stroke and organ damage. Therefore, if voxelotor succeeds in trials, it could become the first disease-modifying drug available for this indication.
The per-protocol data that was reported in December was particularly encouraging. After 12 weeks, a 1,500 mg dose of voxelotor had boosted hemoglobin levels by 1 gram per deciliter or more in 65% of 154 patients ages 12 and up. In the placebo group, only 10% of patients saw that level of improvement. Results on an intention-to-treat (ITT) basis, which is necessary for FDA approval, weren’t provided.
Global Blood also reported numerically fewer cases of vascular occlusive crisis in the voxelotor arm of the study than in the placebo arm, suggesting voxelotor could reduce the risk of hospitalization and improve quality of life.
Unfortunately, updated per-protocol results presented at the European Hematology Association (EHA) on Friday weren't as impressive. In 274 patients, 59.5% of patients taking the 1,500 mg dose achieved a 1 g/dL improvement after 24 weeks. On an ITT basis, 51.1% of patients in that arm of the study saw a 1 g/dL improvement, with an average change of 1.1 g/dL to an average of 9.8 g/dL. The lower percentage of responders on an ITT basis, however, shouldn't worry investors because voxelotor still significantly outperformed the 6.5% responding similarly in the placebo arm.
What is worrisome, though, is voxelotor's inability to significantly and statistically separate itself from placebo when it comes to reducing the risk of vaso-occlusive crisis. The possibility that boosting hemoglobin won't reduce risks of hospitalization and treatment associated with vaso-occlusive crisis raises questions over how much value voxelotor actually delivers to patients and payers. Absent data showing that voxelotor improves quality of life, its commercial opportunity may be smaller than previously thought.
A filing for approval is on deck
Global Blood Therapeutics plans to file for FDA approval of voxelotor in the second half of 2019. If it gets priority review, that could clear the way for a regulatory go/no-go decision in the first half of 2020. Since improving hemoglobin levels is the trial's primary endpoint and reducing vaso-occlusive crisis is secondary, the likelihood of an approval appears good.
Until then, the real debate will be if the data is good enough for payers and doctors to support widespread use of voxelotor, and if Global Blood Therapeutics can charge a premium price for it. For now, investors may want to wait and see how doctors respond to the data currently available to them before buying shares.