PRIME designation for gene therapies for sickle cell anemia

The granting of PRIME designation of two gene therapies for sickle cell anemia gives patients hope for faster access to new therapies.

Sickle cell anemia is a genetic disorder of the erythrocytes caused by a point mutation in the HBB gene. Carrier of this mutated gene build abnormal hemoglobin (sickle hemoglobin, HbS), which tends to form fibrils on oxygen deficiency. The erythrocytes deform into the typical sickle-shaped structures and agglutinate. This leads to occlusion of small arteries and thus to severe pain and organ damage. The disease takes a severe course in homozygous carriers of the mutated HBB gene.

Now, the EMA (European Medicines Agency) granted the PRIME (priority medicines) designation for two-gene therapeutics for sickle cell anemia. PRIME is a scheme by the EMA to make promising medicines for an unmet medical need available to patients faster.

Vertex Pharmaceuticals and CRISPR Therapeutics have received the PRIME designation for their CRISPR/Cas9-based gene therapy CTX001. Hematopoietic stem and progenitor cells (CD34+ cells) are collected from the patient and the erythroid enhancer region of the BCL11A gene is edited using CRISPR/Cas9 to enhance the synthesis of fetal hemoglobin (HbF). Afterwards, the modified cells are transferred to the patient via stem cell transplantation and the resulting differentiated erythrocytes then produce fetal hemoglobin.

Bluebird Bio has received the PRIME designation for LentiGlobin™. For the production of LentiGlobin™, a lentiviral vector is used for genetic engineering. A modified, functional form of the ß-Globin gene (ßA-T87Q-globin gene) is introduced into the hematopoietic stem cells obtained from the patient. The resulting differentiated erythrocytes then produce anti-sickle hemoglobin HbAT87Q. HbAT87Q decreases the proportion of HbS and reduces the appearance of sickle-shaped erythrocytes and thus, associated complications.

By granting PRIME designation to two different gene therapies for sickle cell anemia, affected patients can now hope for faster approval of new forms of therapy.

Author: Dr. Alexandra Maria Alers, GMP Documentation Expert, Valicare