Global Blood Therapeutics Inc (NASDAQ:GBT) just kicked off a phase IIa trial in its lead sickle cell candidate, GBT440. Sickle cell is one of the most underserved areas of global healthcare, and there have bee very few developments in the standard of care treatment for the disease over the past fifty years.
Current options are limited to symptom targeting, rather than addressing the underlying condition, and can be both expensive and limited from an efficacy perspective. There’s a rush to bring new treatments to what is a potentially lucrative market (analysts expect the market in the US to grow at a CAGR of 17.10 percent between 2014-2019). bluebird bio Inc (NASDAQ:BLUE), Baxter International Inc (NYSE:BAX) and Pfizer Inc. (NYSE:PFE) are all pushing candidates through the development process, but the latest initiation from GBT puts it in a competitive position from a first to market perspective.
Here’s a look at the drug and the trial in question, and what to look out for in terms of milestones going forward into the latter half of this year, and beyond into 2017.
So, the drug. It’s called GBT440, and the hypothesis behind its potential clinical application is based on some pretty interesting science. Sickle cell disease is rooted in a mutation called HbS, which leads to deoxygenated hemoglobin molecules changing shape (to the shape of a sickle) and polymerizing (essentially, sticking together). This polymerization causes the problems associated with the condition. Scientists noticed, however, that developing new born babies that have the HbS mutation don’t start to show red blood cell sickling until around six months of age. This is because until six months, they express a special type of hemoglobin only seen in fetuses and new born babies. This special type has an extra high affinity for oxygen, as this high affinity is required for a fetus to capture oxygen from its mother’s blood. Anyway, the takeaway was that there was something that is stopping sickling in fetuses and new borns, and the logical conclusion is that this something is the delayed de-oxygenation of the hemoglobin caused by the high affinity hemoglobin.
GBT440 attempts to mimic this delaying of the de-oxygenation by binding to hemoglobin and increasing its affinity for oxygen uptake. It’s got both fast track and orphan drug designation in the US.
Now let’s look at the trial. It’s a phase IIa, and its attempting to demonstrate a combination of efficacy and tolerability in adolescent sickle cell patients, with adolescent here referring to kids between the ages of 12-17. It’s split into two parts – one will see six patients receive a single dose, and the second will see a further twenty-four patients receive increasing multiple doses across a four-week period. It’s running concurrent to an already established, and ongoing, phase I/II that is exploring the safety and clinical impact of the drug in both healthy and SCD patients over the age of 18. The initial filing of this latter trial suggested a primary completion of April this year, and the company presented some 90-day data that suggested clinical impact and safety at the EHA earlier this month. Global Blood Therapeutics Inc (NASDAQ:GBT) is in talks with the FDA and wants to kick off a pivotal before the close of 2016. This offers an immediate upside potential catalyst, and as far as the non-adolescent indication is concerned, is the major milestone to watch as this development pipeline progresses.
Focusing specifically on the trial in focus here, the adolescent trial, we are looking for interim data to confirm the tolerability expectations, and beyond that, some data that suggests the drug can increase the affinity for oxygen uptake in the blood of the patients in question. This is a baseline measurement secondary endpoint, and will probably be watched more closely than the adverse event side of things come topline, purely because the safety is by this point pretty well established.
So what’s the takeaway here? Well, Global Blood Therapeutics Inc (NASDAQ:GBT) is trading pretty much flat on the announcement, which shows markets are looking to the quantitative side of things rather than the operational as indicative of strength. Data drops, therefore, become of primary importance. In order of expected impact: interim from the just initiated IIa, topline from the same, and, beyond that, a pivotal adult trial initiation.
Note: This article is written by Jennifer Aldershot and originally published at Market Exclusive.