Approval of Novel Therapy for Beta-Thalassemia

Peter L. Salgo, MD: Let me throw another ball in here, just because we’re juggling at this point. There’s a drug—I hate these names—called luspatercept. What is that? Where does that fit into this whole picture?

Maria Domenica-Cappellini, MD: Actually, this is part of the new approach to treatment. Luspatercept is a molecule that was found to possibly be used to treat beta thalassemia by chance versus 7DPT observation, because it was studied for treating osteoporosis in postmenopausal women. And what we’re seeing is that hemoglobin of these normal hematologic ladies went up significantly, so they stopped and said, “What is going on?” Looking in the animal model, luspatercept is a compound that belongs to the beta superfamily growth factor, and it is actually acting as an active receptor clamp. I don’t want to go in to any details, but luspatercept interferes with the receptor controlling the pathway—SMAD pathway, and so on—which is responsible for controlling the erythropoiesis, all of which contribute. Doing that, it’s come out that it is reducing ineffective erythropoiesis.

Peter L. Salgo, MD: Who gets it? Who gets this drug?

Maria Domenica-Cappellini, MD: Well, the phase III trial has just been completed. The FDA approved it.

Peter L. Salgo, MD: That’s, by the way, your trial. Is that right?

Maria Domenica-Cappellini, MD: Well, not only mine. I was the PI [principal investigator], but most of the people—there were, I think, 65 centers all over the world, so it was a fascinating and really nice experience. And the results of this trial were presented to the FDA, which in the beginning of November approved the drug. For whom? For those patients who are transfusion dependent.

Sujit Sheth, MD: Adults.

Peter L. Salgo, MD: This is a grown-up drug.

Maria Domenica-Cappellini, MD: Adult patients, because we don’t have data yet in children. So those who are transfusion dependent. And what do we observe in those patients? A significant reduction of the blood transfusion requirement. Actually, if a patient was on a regular drug transfusion every 2 to 3 weeks in a large proportion of patients in whom you observe significant reduction. To my contributors this is a great improvement, alternative to bone marrow transplantation or other possible methods.

Sujit Sheth, MD: Essentially, you can go from getting 2 units of blood every 3 weeks to possibly getting 1 unit of blood every 3 weeks. That’s a big difference. Or you can go from getting 2 units every 3 weeks to getting 2 units of blood every 4 weeks.

Peter L. Salgo, MD: Again, a big difference.

Sujit Sheth, MD: A big difference because now you’re effective.

Maria Domenica-Cappellini, MD: You know, for some of the patients, we are going to say they decreased more than 50%. Among those groups there are some patients who are becoming transfusion independent.

Sujit Sheth, MD: Independent, yes.

Peter L. Salgo, MD: You had something to say.

Farzana Sayani, MD: No, I totally agree with that.

Peter L. Salgo, MD: You’re agreeing.

Farzana Sayani, MD: And overall it was generally well tolerated. There is some increased risk of thrombosis and hypertension, so we need to monitor that.

Peter L. Salgo, MD: Hyper or hypo?

Farzana Sayani, MD: Hyper. Overall, there were only grade 1 or 2 adverse events, including some joint pain—arthralgias—but overall very well tolerated. So that’s very exciting.

Maria Domenica-Cappellini, MD: And how it is administered, subcutaneously: 1 injection every 3 weeks. We have to be careful anyway or conscious anyway. They can do it at home subcutaneously for the future as patients do insulin or something like that.

Transcript edited for clarity.