Developing Hydroxyurea, the First FDA-Approved Therapy for Sickle Cell Disease

As NIDDK celebrates its 70th anniversary, we look back on decades of scientific advances. In this video, NIDDK Director Dr. Griffin P. Rodgers details the research, clinical trial, and results behind Hydroxyurea, the first FDA-approved therapy for sickle cell disease.

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Transcript:

DR. RODGERS:

This drug Hydroxyurea – that was really the basis of our work in the late 80’s and early 90’s.

There was a group in the Heart, Lung, and Blood Institute who started working on this using a drug called 5-Azacytidine.

Just like all chemotherapy, it first causes some toxicity to the rapidly dividing cells, and then when you withdraw the drug and you give the cells a chance to recover maybe that’s what’s turning on the genes. And that led us to actually consider this drug Hydroxyurea because it’s a form of chemotherapy. It works on rapidly dividing cells. It doesn’t have the same toxicity profile that drugs like 5-Azacytidine does.

Using this drug Hydroxyurea in about 70 percent of hospitalized patients we could turn on their fetal hemoglobin to modest levels and the longer you gave it to them, the higher their values would go. Subsequently our work was replicated by groups in Seattle and Harvard and Johns Hopkins, and that led the NIH to fund this fairly large study, a cooperative randomized clinical trial, which tests whether the drug would in fact have a benefit.

And just to cut to the chase, the study was stopped early, a year early, because one group, which was blinded at the time, was doing much much, better than the other group, and that group was the Hydroxyurea group. In 1990, our paper came out. In 1995, this NIH-supported trial, this large randomized trial, showed that Hydroxyurea was quite beneficial. And in 1998, the FDA approved the drug as the first drug that was approved specifically to treat patients with sickle cell disease.