• Global Blood Therapeutics has in hand positive data from a late-stage study of its sickle cell disease drug, which could be a “promising advancement” in the way the disease is managed, according to an editorial published Friday in the New England Journal of Medicine.
• The HOPE study tested two doses of Global Blood’s voxelotor against placebo to assess whether treatment with the experimental drug would increase hemoglobin levels by a certain amount. After 24 weeks, a significantly greater percentage of patients receiving the higher, 1,500 mg dose of voxelotor achieved that “hemoglobin response.”
• Investors, however, may be wary of how clinically meaningful that data will be, as Global Blood shares were down 5% at market’s open Friday. Ted Love, CEO of Global Blood, told BioPharma Dive his company is filing the higher dose of voxelotor for accelerated approval, a submission that should be complete in the back half of the year.

The FDA has acknowledged that there needs to be more treatment options for sickle cell, a disease affecting around 100,000 people in the U.S. To date, just two therapies hold approvals — including one that is more than 20 years old.

The agency in a 2017 post said it’s willing to grant fast track, breakthrough and orphan drug statuses to sickle cell drugs in development. Global Blood is looking for a speedy review of voxelotor, supported by data from HOPE.

“Dying at age 40 is not normal. Being admitted to the hospital multiple times a year is not normal. Having cognitive brain injury before you’re 10 years old is not normal,” Love said. “This is where sickle cell disease is in the United States of America.”

Full results from HOPE were announced by the company and published in NEJM Friday. They showed that, in an intent-to-treat analysis, 51% of the patients treated with voxelotor 1,500 mg had hemoglobin levels rise by more than 1g per deciliter over the 24-week study period. Similar increases were seen in just 7% of the placebo group.

Global blood claims such increases can cut the risk of stroke 40% and risk of death 60%.

Where voxelotor failed, however, was on a secondary endpoint for vaso-occlusive crisis, a kind of acute pain episode that occurs often for sickle cell patients. Patients on either dose of Global Blood’s drug had just one fewer crisis per year than those on placebo, results that weren’t statistically significant.

Should voxelotor gain approval, Global Blood will have to do a confirmatory study to prove its benefit. The company is setting up the trial to have a primary endpoint of reducing stroke rather than reducing the pain episodes.

“Vaso-occlusive crisis is something that is important in sickle cell disease — but, arguably, losing your brain function and losing your life are more important,” Love said.

Alexis Thompson of Northwestern University’s Feinberg School of Medicine noted in the NEJM editorial that a 72-week analysis of HOPE may show a cumulative reduction in these pain episodes for voxelotor-treated patients.

“Follow-up studies are needed to examine this very important, clinically relevant endpoint,” Thompson wrote.

Hemoglobin levels in the 1,500 mg voxelotor group increased from a mean of 8.6 g per deciliter at baseline to a mean of 9.8 g per deciliter after 24 weeks, which Global Blood said is “consistent with a clinically meaningful improvement in anemia.”

Typically, people have between 12 g and 17 g of hemoglobin.

On safety, 26% of both the placebo and 1,500 mg voxelotor arms experienced grade 3 or higher side effects, though investigators concluded most weren’t related to either treatment.

Global Blood has not revealed the intended list price for its drug, though Love said companies bringing new sickle cell therapies to market need to make sure patients have access to them.

“We are committed to that. We are committed to providing free drug. We are committed to providing patient assistance,” he said.