Gene-editing Therapy CTX001 Granted RMAT Status by FDA for Severe SCD

The U.S. Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation to CTX001, an investigational gene-editing cell therapy, for the treatment of severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).

The announcement was made by CRISPR Therapeutics and Vertex Pharmaceuticals, which are working together to develop CTX001.

RMAT is given to expedite the development and review of new therapies whose main purpose is to treat medical conditions considered serious or life-threatening, or when they show significant clinical benefits over existing therapies. As with the FDA’s breakthrough therapy designation, cell or gene therapies that receive RMAT designation may benefit from early interactions with the FDA and be eligible for priority review and accelerated approval.

CTX001 uses the CRISPR-Cas9 gene-editing tool to modify patients’ blood cell precursors (hematopoietic stem cells) so that they produce high levels of fetal hemoglobin in red blood cells. Once gene editing is complete, the cells are re-introduced back into patients in the form of a stem cell transplant.

Fetal hemoglobin is a form of hemoglobin found in newborns that is more effective at transporting oxygen compared to the version of the protein found in adults.

By increasing the levels of fetal hemoglobin, CTX001 is expected to lower the frequency of vaso-occlusive crises (VOCs) in SCD patients and the constant need for blood transfusions in those with TDT, which are brought on by defects in the adult form of hemoglobin they produce.

“RMAT designation is another important regulatory milestone for CTX001 and underscores the transformative potential of a CRISPR-based therapy for patients with severe hemoglobinopathies,” Samarth Kulkarni, PhD, CEO of CRISPR Therapeutics, said in a press release.

“We expect to share additional clinical data on CTX001 in medical and scientific forums this year as we continue to work closely with global regulatory agencies to expedite the clinical development of CTX001,” he added.

Preliminary data from the Phase 1/2 CLIMB-SCD-121 trial (NCT03745287), which is assessing the safety and effectiveness of a single dose of CTX001 in patients with severe SCD, has shown that the therapy safely increased the levels of fetal hemoglobin in the first patient dosed, effectively preventing the occurrence of VOCs.

As of the last update (November 2019), this study was still enrolling participants at several sites across the U.S., Canada, and the European Union. More details can be found here.

Positive early findings have also been reported for the first TDT patient receiving CTX001 in the Phase 1/2 CLIMB-Thal-111 trial (NCT03655678, also still recruiting).

“The first clinical data announced for CTX001 late last year represented a key advancement in our efforts to bring CRISPR-based therapies to people with beta thalassemia and sickle cell disease and demonstrate the curative potential of this therapy,” said Bastiano Sanna, PhD, executive vice president and chief of cell and genetic therapies at Vertex.

In addition to RMAT, CTX001 previously received orphan drug designation from the FDA for the treatment of TDT and from the European Medicines Agency (EMA) for both TDT and SCD. The therapy has also received fast track status from the FDA for both disorders.

“We are encouraged by these recent regulatory designations from the FDA and EMA, which speak to the potential impact this therapy could have for patients,” Sanna said.