Global Blood Therapeutics ($GBT) has posted an upbeat update from a small clinical trial of its sickle cell disease drug, GBT440. The data, which show the effects of GBT440 last for three months or more, have allayed concerns about the durability of responses to the drug, sparking a 25% jump in the company’s stock price.
After treating 6 patients with 700 mg daily doses of GBT440 for 90 days, GBT detected a 37% fall in levels of unconjugated bilirubin, a substance that is released when the liver breaks down red blood cells. As sickle cell forms of red blood cells have shorter lifespans than their healthy counterparts, a fall in the levels of bilirubin indicates that GBT440 is stopping cells from deforming and ultimately from being broken down. Bilirubin levels increased by 20% in the two-person placebo arm.
These data suggest GBT440 is succeeding in preventing red blood cells from stiffening, taking on the characteristic sickle shape and being broken down prematurely. This disease pathway is driven by the polymerization of hemoglobin. GBT440 is designed to stop this process by ensuring the hemoglobin is oxygenated, a state that stops it from deforming. GBT is now confident the drug is working in this regard.
"I don't want to oversell the data we have, but I am confident that we have a drug which impairs polymerization,” GBT CEO Ted Love told The Street.
The impression that GBT440 is having a positive effect on the condition of the 6 participants was backed up by a look at their counts of immature red blood cells. Sickle cell disease is associated with high levels of these cells, known as reticulocytes, because the body produces them in large numbers in an attempt to counter the loss of the deformed cells. After 90 days, reticulocyte levels in the GBT440 were down by around 20%, compared to a 20% increase in the placebo group.
GBT had previously presented data to show GBT440 has an effect on sickle cell disease, but it lacked results demonstrating the response was maintained far beyond the first month of treatment. Worse still, the final days of those data showed hemoglobin levels falling after an early surge. The data update, which GBT released at the European Hematology Association Congress in Copenhagen, goes some way to allaying the durability doubts, while also bolstering the safety profile of the drug.
Investors responded by driving shares in the company up by 25% in premarket trading. The uptick reflects hopes that GBT can get the drug into a pivotal trial later this year and deliver the data it needs to win approval. “Next for us will be to gather all the data and sit down with the FDA to settle on a pivotal trial design," Love said.