Hematology Meeting Presents Information of Interest for Thalassemia

December 9, 2015 – The American Society of Hematology (ASH) held its annual meeting from Dec. 4 – 8 in Orlando, FL, and CAF was once again there to distribute information, meet with clinicians and researchers and attend educational and scientific meetings of relevance to the thalassemia community. Below is information on a few of the developments of interest to thalassemia which were discussed at the meeting.


Antonio G. Piga, MD, of the Azienda Ospedaliero-Universitaria San Luigi Gonzaga in Turin, Italy, presented data from Celgene and Acceleron Pharma’s ongoing Phase 2 clinical trial investigating luspatercept, a protein that aims at increasing the production of mature red blood cells.

Dr. Piga

The study involves 31 non-transfusion-dependent thalassemia (NTDT) patients and 28 transfusion-dependent (TD) thalassemia patients over a 12-week period. Patients received luspatercept via subcutaneous injection once every 3 weeks. Patients who completed the 12-week trial were given the option of continuing in an extension trial; 51 patients have enrolled in this trial.

The data presented indicated that that luspatercept increased hemoglobin levels and reduced transfusion burden, Specifically, 65% of the NTDT patients who received the higher dose levels obtained increased hemoglobin levels by at least 1.0 g/dL; 47% of them increased hemoglobin levels by 1.5 g/dL. Among TD patients 79% had at least a 20% reduction in transfusion burden; 57% had at least a 50% reduction in transfusion burden.

In addition, data suggests that luspatercept improved health-related quality of life measures and had beneficial effects on liver iron concentration.

Luspatercept will be further studied among thalassemia major patients in a new Phase 3 clinical trial (the “BELIEVE” trail), which is recruiting patients in the United States for an expected January 2016 start date.

Gene therapy

Dr. Walters

Mark C. Walters, MD, UCSF Benioff Children’s Hospital Oakland, reported on the HGB-204 “Northstar” trial being conducted by bluebird bio. This is an ongoing clinical trial investigating safety and efficacy in gene therapy processes involving the LentiGlobin BB3305 drug product.

The results reported suggest that a patient’s exact thalassemia genes may be an important factor in determining whether the gene therapy can lead them to be entirely off transfusions with gene therapy, or if some transfusions are still required. The patient numbers are still very small, but five patients in the trial who make some beta globin (as opposed to none) have been transfusion free since their gene therapy 7-16 months ago, while four others who make no beta globin still require some transfusions, though less than before.

Dr. Cavazzana

In a separate report, Marina Cavazzana, MD, PhD, of Hôpital Universitaire Necker -Enfants Malades presented data from another LentiGlobin BB3305 product study (HGB-205). Two patients with e beta thalassemia have remained transfusion free for at least 15 months; a third patient (thalassemia major) has been treated but it is too soon to report results on that patient at this time.

Globin gene therapy is but one possible approach now for thalassemia gene therapy. Another is provided in the next section on BCL11A


Dr. Urnov

Further data was presented on BCL11A gene modification, and its potential role in treating thalassemia. After a baby is born, its fetal hemoglobin is gradually replaced by adult hemoglobin, and BCL11A plays a vital role in that replacement by helping to repress fetal hemoglobin. Fyodor Urnov, PhD, of Sangamo BioSciences reported on a novel approach using genome editing to “knock out” the BCL11A controlling sequences (called an enhancer) specifically in cells that will eventually become red blood cells. This allows BCL11A to stay low and allows the fetal hemoglobin levels to rise, which has the potential to beneficially affect thalassemia. In mouse models, the results have been positive and the data is encouraging.

“ASH 2015 in Orlando was a very exciting meeting,” states Ellis J. Neufeld, MD, PhD, chair of CAF’s Medical Advisory Board. “In many areas of blood diseases, entirely new kinds of drugs, gene therapy and gene editing are emerging as possible treatments. The clinical trials are still quite early, but these three examples – luspatercept, globin gene therapy, and the possibility of BCL11A gene editing – show real promise for thalassemia patients.”

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