CHMP backs Casgevy, sickle cell gene-editing therapy, for EU

European Commission due to decide on therapy's approval in February

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A European Medicines Agency committee has issued a positive opinion on the gene-editing therapy Casgevy (exagamglogene autotemcel) in treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).

The Committee for Medicinal Products for Human Use (CHMP) recommendation will be considered by the European Commission in making a final approval decision on Casgevy, which is expected in February. While the commission does not have to align with a CHMP opinion, it often does.

“This positive opinion is yet another important regulatory milestone underscoring the potentially transformative benefit of Casgevy for eligible patients with sickle cell and transfusion-dependent beta thalassemia,” Nia Tatsis, PhD, executive vice president and chief regulatory and quality officer at Vertex Pharmaceuticals, said in a company press release.

Vertex co-developed Casgevy — formerly known as exa-cel — with CRISPR Therapeutics.

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A European Union (EU) approval would cover patients 12 and older with severe SCD and recurrent vaso-occlusive crises (VOCs) or with TDT, who are eligible for a stem cell transplant but a donor is not available. Casgevy recently was conditionally approved in the U.K for these same patient groups.

The U.S. Food and Drug Administration (FDA) approved Casgevy in early December for SCD patients, 12 and older, who experience recurrent VOCs. An FDA decision for TDT is expected in March.

Both SCD and TDT are characterized by a lack of functional hemoglobin, the protein in red blood cells responsible for carrying oxygen.

In TDT, not enough hemoglobin is produced. In SCD,  the production of a faulty version of hemoglobin causes red blood cells to take on a sickle-like shape and clump, blocking blood vessels. That leads to painful VOCs, a hallmark SCD symptom due to a lack of oxygen arriving for patients’ tissues.

“There is an urgent need for new potentially curative treatments in beta thalassemia and sickle cell disease, as people with these diseases still have a shorter life expectancy than the general population and an impaired quality of life,” said Franco Locatelli, MD, PhD, principal investigator of the CLIMB clinical trials that supported Casgevy’s benefits in SCD and TDT patients.

Casgevy — the first gene-editing therapy approved for SCD and the first FDA-approved treatment using the Nobel Prize-winning CRISPR/Cas9 gene editing technology — works to enable patient’s own blood cells to produce more fetal hemoglobin. Fetal hemoglobin, which is more efficient at carrying oxygen than adult hemoglobin, is normally generated during fetal development but turned off sometime after birth.

Higher levels of this healthy version of hemoglobin are expected to prevent red blood cell sickling, easing VOCs in SCD patients.

People in Phase 2/3 trial reported meaningful life gains with treatment

That’s supported by data from the Phase 2/3 CLIMB-121 clinical trial (NCT03745287), where nearly all treated patients with severe SCD were free of severe VOCs and hospital admissions for at least 12 consecutive months. Across several patient-reported outcome measures, trial participants reported sustained and clinically meaningful life quality improvements.

CLIMB–111 (NCT03655678), a similarly designed trial involving TDT patients, also demonstrated clinical benefits with a one-time infusion of Casgevy. Patients from both trials are being monitored for treatment safety and efficacy for up to 15 years in the ongoing CLIMB-131 extension study (NCT04208529).

“As an investigator, I have witnessed first-hand the transformative impact [Casgevy] can have on patients’ lives and I eagerly await the approval in the European Union,” said Locatelli, a professor at the Catholic University of the Sacred Heart and director of pediatric hematology and oncology at the Bambino Gesù Children’s Hospital, both in Rome.

The FDA, in announcing Casgevy’s U.S. approval on Dec. 8, also approved a gene therapy by Bluebird Bio being marketed as Lyfgenia (lovotibeglogene autotemcel).

Lyfgenia, formerly known as lovo-cel or LentiGlobin, has been given orphan drug and priority medicines designations in Europe.