GBT heads into Ph III, pivotal testing for sickle cell candidate

Blood

Global Blood Therapeutics ($GBT) will start lining up patients in December for a Phase III, pivotal trial of its GBT440 to treat sickle cell disease (SCD). Top-line data from the study is anticipated during the first half of 2019.

GBT440 is expected to be an oral, once-daily SCD treatment. It’s designed to restore normal hemoglobin function—and to possibly modify the progression of the disease. GBT440 blocks polymerization and the resulting sickling of red blood cells by increasing the hemoglobin’s affinity for oxygen. The FDA has already granted both fast track and orphan drug designations to the candidate for the treatment of SCD.

“This agreed-upon study design underscores our common goal to address the urgent unmet medical need for new disease-modifying preventative therapies for SCD and the importance of innovative regulatory strategies to bring new therapies to market to treat these patients,” said GBT President and CEO Dr. Ted Love in a statement.

He added, “The HOPE Study design has a strong grounding in GBT440’s mechanism of action, including its potential to fundamentally modify the course of the disease by inhibiting sickle hemoglobin polymerization.”

The Phase 3 HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS PolymErization) Study will be conducted at leading SCD sites globally and will enroll adults and adolescents with SCD who have had at least one episode of vaso-occlusive crisis (VOC) in the previous year.

It’s a randomized, double-blind, placebo-controlled trial that will be conducted in two parts. The first part is dose-ranging with 900 mg and 1,500 gm of GBT440 versus placebo; this will include up to 150 patients. The second part will include 250 patients who are randomized to placebo or a dose of GBT440 that’s based on the first part.

The primary endpoint for the HOPE study will be the proportion of patients who achieve a >1 g/dL increase in hemoglobin at 24 weeks of treatment vs baseline. GBT said the FDA is looking for the HOPE trial to meet the primary endpoint as well as one or more of the secondary endpoints that include SCD symptom exacerbation and SCD symptoms as compared to placebo. These will be based on patient-reported data from a hand-held electronic device intended to capture SCD symptom information daily.

GBT440 is the lead candidate for the South San Francisco, CA-based biotech. GBT went public in a $120 million IPO last August that priced at $20 per share and traded up to over $50. It’s now below that offer price at around $18 a share, with a market cap of about $665 million.

This summer, GBT shares jumped to above $25 each on a positive update for a Phase I/II clinical trial for GBT440 in SCD. The company had about $232 million in cash at the end of the last quarter with an operating loss of $34.5 million during the first half of the year.