Drug Development

FDA clears Global Blood Therapeutics to focus on key biomarker in pivotal sickle cell trial

Just days after fleshing out its latest set of positive data from a tiny study of GBT440 for sickle cell disease, Global Blood Therapeutics $GBT says that the FDA has signed off on its pivotal trial design, agreeing to stick with a key biomarker for hemoglobin levels for the primary endpoint, which investigators have already successfully tried out in smaller trials.

Earlier in October, the biotech reported that among six patients receiving treatment over 90 days there was a “median 1.1 g/dL (gram per deciliter) increase in hemoglobin concentration with GBT440 treatment compared with a “0.2 g/dL decrease with placebo.”

That’s the same endpoint GBT has now gathered positive data on from about 50 patients, CEO Ted Love told me in a preview of his post-market announcement today. And its used as the primary endpoint in a late-stage study — the first Love has heard of in sickle cell disease — which will likely come as quite a surprise to many of the observers in this field, he adds.

“I think many people felt that it was simply a surrogate endpoint,” says Love. But the biotech is shooting to see the same kind of effect a doctor would look for in ordering a blood transfusion for a particularly anemic patient, which should translate into improvements for at least one in a slate of secondary endpoints that are being included in the trial.

GBT’s shares shot up 18% in post-market trading following the news break.

The most likely immediate benefit should be reflected in a reduced burden of fatigue many patients are afflicted with, says Love, adding that pain and fatigue are the two big symptoms that patients have to deal with.

The South San Francisco-based biotech will use that marker in a much, much larger study than it has ever tackled before, with about 400 patients expected to be recruited. The trial will be run in two stages, starting with two doses to identify the best approach for stage two. The full study will test the drug over at least 24 weeks.

Final data should be out in 2019, though GBT execs say that they also expect to review the results from the first stage of the trial, when it’s available.

Their endpoint marks a big switch from other studies which have focused on the rate of vaso-occlusive crisis (VOCs), its investigators say, when sickle cell shaped red blood cells occlude small blood vessels, spurring inflammation, injury and intense bouts of pain. Pfizer went with VOCs for its rivipansel Phase III. The penny biotech Mast Therapeutics, for example, recently missed the VOC endpoint, wiping out much of what was left of its market cap.

Previous SCD studies have generally focused on VOC, defined as a painful crisis requiring hospital or emergency room utilization. But we know that patients have 4-5 times more frequent painful crises, with or without utilization. As a result, the burden of painful crises is dramatically under-reported,” said Wally Smith, M.D., Florence Neal Cooper Smith Professor of Sickle Cell Disease Director, a comprehensive sickle cell program at Virginia Commonwealth University, in a statement. “By utilizing the PRO, the innovative design of the HOPE Study should allow measurement of the true burden of SCD painful crises and other symptoms.

Secondary outcomes include: The effect of the drug on symptom exacerbations measured by the company’s Patient Reported Outcome instrument; VOCs; hospitalizations and red blood cell transfusions.

In a corporate update after the release, GBT execs added that their CMO, Eleanor Ramos, opted to resign effective today, adding that they have enough cash to get into Q2 of 2018 — look for a financing at an opportune moment — as they cover a study likely to cost about $40 million. In addition, GBT is dropping a preclinical study for GBT18713, an oral kallikrein inhibitor for the prevention of hereditary angioedema attacks, so they can focus on their lead work.


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