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GBT Eyes Fast Nod for Sickle Cell Drug but Won’t Use Patient-Reported Data

Xconomy San Francisco — 

Global Blood Therapeutics hasn’t finished testing its treatment for sickle cell disease, but the South San Francisco, CA-based company thinks it can get a fast-track approval for the once-a-day pill, voxelotor, from the FDA.

That was the company’s message this morning when it presented results from the first half of its key Phase 3 study, known as HOPE. Part A of the study continued voxelotor’s track record from previous studies. In two different doses, the drug significantly boosted levels of the protein hemoglobin, which carries oxygen and is crucial to the healthy function of red blood cells. The news bumped Global Blood (NASDAQ: GBT) stock price more than 15 percent Wednesday, to close at $44.75.

Part A was designed as a prelude to Part B—to find the right dose of voxelotor, and set up a way to record patient-reported experiences to include in the study’s final results.

Those experiences, known as patient-recorded outcomes, were potentially to be a key part of HOPE and had sickle cell patients anticipating more of a say in the study. In an interview last month, Lakiea Bailey, executive director of the Sickle Cell Community Consortium in Atlanta, praised Global Blood for “working in a patient-centered framework and having their own set of patient-reported outcomes.” Bailey said today she needed to review the news before commenting.

Those outcomes will not factor into voxelotor’s eventual evaluation, however. The company said today that the data that patients provided “were difficult to interpret”—study participants were using a phone app to record their daily levels of pain and other symptoms by answering a short series of questions.

But Global Blood believes that the main test for voxelotor—the boost in hemoglobin levels by at least 1 gram per deciliter—will be enough to gain FDA approval. At a 1500 mg dose, 58 percent of patients had a greater than 1 g/dL boost in hemoglobin over 12 weeks. At a lower 900 mg dose, it was 38 percent of patients. Placebo was 9 percent. On a conference call this morning, CEO Ted Love said the study would likely continue at the higher dose, 1500 mg, but no final decision on the final dose has been made.

Even without patient-reported outcomes, Global Blood counted pain episodes, but the reduction they saw in the two voxelotor arms was not statistically significant. The company is counting on the FDA to mainly consider the hemoglobin boost when evaluating the drug because of what Love called a “well-documented correlation” between low hemoglobin levels, organ damage, and premature death. The agency has used other so-called biomarkers to approve drugs, especially when there is a strong correlation of the biomarker with real-world improvements. (Lowering cholesterol, for example, leads to better heart health.)

“Our discussions with FDA are about that,” said Love. “If we continue to show additional evidence that this is safe, it would be the basis for initial approval, then we would follow with studies to confirm the clinical benefit.”

The FDA is increasingly willing to approve drugs based on biomarkers or other signals that don’t conform to the traditional pathway for approval. Often the promise is that companies will indeed follow with larger studies to show improvements in patient health, but drugs are rarely if ever removed from the market because of a lack of efficacy.

Sickle cell disease stems from a genetic mutation in the hemoglobin gene, which results in crescent-shaped red blood cells, instead of healthy round ones. The misshapen cells cannot carry enough oxygen, often leading to organ damage, stroke, and other deadly problems. The cells also clog blood vessels and cause excruciating pain episodes, or “crises,” that often require hospitalization.

Only two drugs have been approved to treat the symptoms. One is a repurposed chemotherapy, the other is a version of a dietary supplement. Beyond medicines, there are blood transfusions and ever more sophisticated plans to improve lives. But even with the best care possible, symptoms can shorten a person’s life by decades. There is a cure—bone marrow transplant—but for several reasons it is rarely an option. Even when it is, there is risk of lethal complications.

Image courtesy of Scooter DMU via a Creative Commons 2.0 license.