Updated from 8 am EDT with new clinical trial data.

SAN DIEGO — Global Blood Therapeutics (GBT) said Monday that it had reached an agreement with the Food and Drug Administration for an accelerated approval submission of its experimental drug to treat sickle cell disease.

It is a major win for the South San Francisco-based biotech — and a sign of new flexibility at the FDA, which will allow the company to try to secure faster approval for its drug in a way never used before in sickle cell disease.


The submission plan agreed to by the FDA will encompass data from a completed clinical trial showing the drug, voxelotor, safely increases hemoglobin, the oxygen-carrying molecule in red blood cells. By raising hemoglobin, Global Blood believes voxelotor is reasonably likely to reduce the frequency of strokes in sickle cell disease patients.

But under the accelerated approval pathway, the company won’t need to conduct a clinical trial proving voxelotor reduces strokes until after the drug is approved.

Traditionally, the FDA has only approved a drug for sickle cell disease based on scientific proof demonstrating a reduction in the frequency of sickle “crises.” Also known by the shorthand “VOCs,” these are the searingly painful and potentially life-threatening exacerbations of the disease that occur when misshapen red blood cells clump inside blood vessels.

Global Blood does not have any data from its completed clinical trial connecting voxelotor to lower crises or even data showing that the drug improves patients’ quality of life. By agreeing to consider voxelotor for accelerated approval based on hemoglobin data alone, the FDA is ceding to demands from the sickle cell community that new drugs reach the market faster.

“This is a big deal and a huge move for the FDA,” Josh Lehrer, Global Blood’s senior vice president of development, told me Sunday night.

It was also an unprecedented regulatory gamble on the part of Global Blood that critics (myself included) said had a high risk of failing. The FDA has relied on reduction in pain crises as the approval benchmark for sickle cell disease because it is the most clinically meaningful outcome about which patients care the most, many experts believe.

Global Blood proved the doubters wrong.

“The FDA does not expect us to show that voxelotor has a benefit in VOC,” said Global Blood CEO Ted Love, also speaking to me on Sunday night. “The FDA is of the view, I think, that if you can preserve the brains of children, maybe that’s better than VOC. And that’s why we’ve embraced the idea of preserving organ function by raising hemoglobin and improving oxygenation in people with sickle cell disease who don’t have adequate oxygenation.”


Sign up for Go West — our new rundown of West Coast life sciences, health care, and biotech

Please enter a valid email address.

Dr. Alexis Thompson, president of the American Society of Hematology and a sickle cell disease expert at Northwestern’s Feinberg School of Medicine, believes there is a need to move beyond pain crises as the only approvable endpoint for sickle cell disease.

“ASH has long-standing partnership with the FDA and we support their process. If the FDA says there is sufficient evidence and there is some possibility of effectiveness, then we are open to hear more about it,” she said.

Sickle cell disease is an inherited disorder resulting from a mutation in the gene for hemoglobin. Voxelotor is a daily pill that makes oxygen attach more tightly to the molecule. By keeping hemoglobin in a highly oxygenated state, the mutation that causes sickle cell disease is covered up, helping the red blood cells maintain a normal shape and preventing them from clumping together inside blood vessels.

Love stressed that the agreement reached with the FDA does not guarantee voxelotor’s approval, only that the drug’s marketing application will be accepted and reviewed under accelerated approval guidelines. The company must still satisfy the FDA that the drug raises hemoglobin and does it safely.

If voxelotor is approved, Global Blood will be required to conduct a confirmatory study, which will use an imaging technique known as transcranial doppler to measure improvement in blood flow to demonstrate stroke reduction.

A full presentation of the voxelotor clinical trial results showing further details on the hemoglobin increase took place this morning at the annual meeting of the American Society of Hematology. Those data are described below. The company announced top-line results from this study last June.

Global Blood is not disclosing precisely what the FDA said about the accelerated approval filing plan, but in his comments to me, Love left little wiggle room for misinterpretation.

“The FDA was very clear. They told us that this idea of filing on the basis of hemoglobin data, through Subpart H [accelerated approval], is acceptable. They said that to us in writing and in verbal conversation.”

And then he added: “Unless I’m incredibly stupid, I wouldn’t get up in front of people and say stuff that the FDA will later say, ‘We didn’t agree to that.’”

Update: Global Blood followed up its FDA announcement with a presentation of the voxelotor clinical trial at the ASH meeting. The study enrolled 154 patients with sickle cell disease and treated them with one of two doses of voxelotor or a placebo. The results: 65 percent of patients on the higher dose of voxoletor achieved a hemoglobin response, defined as an increase in hemoglobin of at least one gram per deciliter after 24 weeks.

On the lower dose of voxelotor, 33 percent of patients had a hemoglobin response. This compared to a 10 percent hemoglobin response for placebo patients. The benefit for voxelotor at both dose levels was statistically significant, meeting the primary endpoint of the study.

On average, the patients treated with the higher dose of voxelotor saw their hemoglobin increase to 10 grams/deciliter at 24 weeks from a baseline start of 8.6 grams/deciliter. The lower dose of voxelotor provided a smaller hemoglobin boost, while there was no change in hemoglobin among placebo patients.

The study also showed that both voxelotor doses produced statistically significant reductions in hemolysis, or the destruction of red blood cells, compared to placebo. This finding confirms the hypothesis that the drug protects red blood cells in sickle cell patients.

Among the patients treated with voxelotor, there were fewer episodes of pain crises caused by sickled red blood cells clumping inside vessels, compared to placebo. The annualized rate of crises was 3.41 events per year in the placebo, falling to 2.85 and 2.75 events per year in the low and high voxelotor dose groups. The difference was not statistically significant, however.

Leave a Comment

Please enter your name.
Please enter a comment.

Sign up for our Daily Recap newsletter

A roundup of STAT’s top stories of the day in science and medicine

Privacy Policy