Most important, the study's primary efficacy endpoint will measure the ability of GBT440 to increase levels of oxygen-carrying hemoglobin in sickle cell patients compared to a placebo, Global Blood said.
That's a potentially easier efficacy threshold for GBT440 to achieve in sickle cell disease compared to what's historically been required by the U.S. Food and Drug Administration.
Typically, FDA has mandated any drug aimed at treating sickle cell disease demonstrate a reduction in the frequency of painful and damaging sickle cell crises. These "vaso-occlusive crises" are caused by clumps of sickled red blood cells blocking blood vessels.
Global Blood says the FDA agreed on the design of the GBT440 phase III study, including the use of the hemoglobin primary endpoint. However, the agreement on study design and the data required for the drug's approval is not guaranteed in writing with a Special Protocol Assessment (SPA.)
"We did not pursue an SPA. Had we done it, we could have gotten one but it would have taken longer," said Global Blood CEO Ted Love, in a phone interview Monday afternoon.
Global Blood wants to start screening sickle cell disease patients for the phase III study in December with the hope of having top-line results in the first half of 2019.
"I don't think FDA felt we needed an SPA," Love added. "Our process with the FDA was trying to reach an agreement because this study is important for us and for the agency. I do know this decision [the trial design agreement] was endorsed at the highest levels of the FDA, based on our discussions with them."
Global Blood's GBT440 works by modifying hemoglobin, the oxygen-carry protein inside red blood cells. GBT440 makes oxygen attach more tightly to hemoglobin. By keeping hemoglobin in a highly oxygenated state, the mutation which causes sickle cell disease is covered up, preventing red blood cells from becoming deformed and clumping together.
GBT440 is a pill which sickle cell patients would take once daily for the rest of their lives.
Global Blood's phase III study will enroll 400 patients with sickle cell disease who have had at least one episode of vaso-occlusive crisis in the past year.
The primary endpoint is the proportion of patients who achieve at least 1 g/dl increase in hemoglobin after 24 weeks of treatment with GBT440 or a placebo. The key secondary endpoint will be the effect of GBT440 versus placebo on reductions in the frequency and severity of sickle cell symptoms, as reported by patients.
The study will also examine reductions in vaso-occlusive crises and hospitalizations but the drug's approvability won't hinge on these parameters, as other sickle cell disease drugs have in the past, Love said.
As part of the trial design agreement, the FDA wants Global Blood to demonstrate that increasing hemoglobin with GBT440 leads to improved patient outcomes. For full approval, the study must achieve the primary endpoint and one or more of the secondary endpoints, the company said.
"If you increase hemoglobin by this amount, people are going to feel better," said Love, referring to the efficacy requirement to show a hemoglobin increase of at least 1 g/dl. "They're going to feel less fatigued. They're going to have the capacity to do more things with higher levels of energy."
Global Blood lobbied FDA to use hemoglobin increase as the primary endpoint of the phase III study based on results from a small phase II study of GBT440.
The company last presented data from this phase II study in June. Six sickle cell patients treated with a 700 mg dose of GBT440 for three months showed a median hemoglobin increase of 1.1 g/dl compared to a 0.2 g/dl decrease in placebo patients. The GBT440-treated patients also showed other positive improvements in the health and function of their red blood cells.
Global Blood will be presented updated data from this study, including patients treated at a 900 mg dose of GBT440, at the American Society of Hematology annual meeting.
The phase III study will utilize a 900 mg and a 1,500 mg dose of GBT440, based on favorable safety and continuing efficacy seen in the phase II study, Love said.
Global Blood shares were down 6% to $17.22 in Monday trading ahead of the GBT440 phase III trial design announcement. The stock has lost 45% of its value this year.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.