GBT440 is an oral, once-daily hemoglobin modifier, originally developed for patients with sickle cell disease (SCD), being tested in patients with hypoxemia (abnormally low levels of oxygen in the blood) associated to pulmonary disorders like IPF. GBT440 works by increasing hemoglobin’s affinity for oxygen.
The GBT440-006 study is a randomized, double-blind, and placebo-controlled trial to evaluate the drug’s safety, tolerability, pharmacokinetics, and effect on hypoxemia in IPF patients. Up to 18 people will be enrolled and randomly given in one of two dose levels (of GBT440 or placebo), administered orally for 28 days. Another 12 patients may be enrolled after an independent review of the trial’s safety, potentially raising the total number of participants to 30.
Secondary endpoints in the will evaluate the change from baseline in oxygen saturation, both at rest and after exercise.
“Current treatment for IPF is targeted at slowing lung fibrosis but there has been no improvement in oxygenation and symptom burden of the disease. Supplemental oxygen therapy, which is used to treat the hypoxemia and its associated breathlessness, has local and systemic risks and poses a significant burden to patients,” Ted W. Love, MD, the company’s chief executive officer, said in a press release. “[T]here is a critical need for a therapeutic drug that can improve oxygenation without those risks and improve quality of life.”
Proof of concept for GBT440 analogs have been established in three animals models, Dr. Love added, “suggesting that hemoglobin modification may increase oxygen saturation and improve oxygen delivery to tissues. Based on those data, we believe that GBT440 is a promising therapeutic option for IPF.”
Hypoxemia can lead to tissue hypoxia (a deficiency in the amount of oxygen that reaches the tissues), which is thought to play a key role in IPF progression. Recent data suggested that GBT440-like hemoglobin modifiers may re-establish normal hemoglobin function and increase oxygen uptake in the lungs, leading to improved oxygen delivery to patient’s tissues.