Casgevy gene therapy conditionally approved in EU for SCD and TDT

Treatment now will be available to 8K patients, ages 12 and older, in Europe

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The European Commission has granted conditional approval to the gene-editing therapy Casgevy (exagamglogene autotemcel) for patients ages 12 and older with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT), two blood disorders.

Eligible patients include those with SCD who experience recurrent vaso-occlusive crises (VOCs) and TDT patients who are eligible for a stem cell transplant but don’t have an available donor.

This decision will make the treatment available to around 8,000 people living in Europe, according to Vertex Pharmaceuticals, which co-developed Casgevy along with CRISPR Therapeutics.

Casgevy was conditionally approved late last year for the same patient groups in the U.K. The therapy also is approved for similar indications in the U.S. and Saudi Arabia.

“With this approval, Casgevy is now approved for sickle cell disease and transfusion-dependent beta thalassemia in multiple geographies making tens of thousands of patients eligible for this potentially transformative therapy,” Reshma Kewalramani, MD, Vertex’s president and CEO, said in a company press release.

“Now our goal shifts to translating these approvals into real-world patient benefit and ensuring access and reimbursement across the globe,” Kewalramani said.

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To ensure patient access to Casgevy across the European Union, Vertex already is engaging with authorities across multiple countries. The company said it’s secured early access to patients in France ahead of the national reimbursement process.

Casgevy must be administered at an authorized treatment center (ATC) with appropriate expertise in stem cell transplants. Vertex is working with hospitals across Europe to broaden the ATC network and plans to have a total of 25 centers in the region; three are now active.

“Sickle cell disease and transfusion-dependent beta thalassemia are debilitating, life-shortening diseases associated with significant burden on patients, families and health care systems,” said Franco Locatelli, MD, PhD, the principal investigator of the clinical trials backing the regulatory approvals.

“Casgevy offers the potential of a functional cure, and it will be important to offer this therapeutic option to eligible patients as soon as possible,” added Locatelli, who also is a professor at the Catholic University of the Sacred Heart and a physician at the Bambino Gesù Children’s Hospital, both in Rome.

SCD is characterized by the production of a faulty version of hemoglobin — the protein in red blood cells responsible for carrying oxygen — that causes red blood cells to take on a sickle-like shape and clump up.

Consequently, blood vessels can become blocked and oxygen transport to tissues is compromised, leading to painful VOCs. TDT is a related condition in which there is a lack of hemoglobin production.

A one-time treatment, Casgevy uses CRISPR/Cas9 gene-editing technology to boost the production of fetal hemoglobin, a version of hemoglobin that’s produced during fetal development, but is normally suppressed sometime after birth.

Increases in fetal hemoglobin production are expected to prevent red blood cells from sickling, thereby easing VOCs for SCD patients.

Casgevy offers the potential of a functional cure, and it will be important to offer this therapeutic option to eligible patients as soon as possible.

A European Medicines Agency committee issued a positive opinion on Casgevy for the treatment of SCD and TDT in December. It was backed largely by findings from the Phase 2/3 CLIMB-121 clinical trial (NCT03745287), where nearly all treated SCD patients remained free of severe VOCs and hospital admissions for at least 12 consecutive months, or longer than one year.

A similarly designed trial, CLIMB–111 (NCT03655678), demonstrated clinical benefits in TDT patients.

The conditional approval from the European Commission means that Vertex can market Casgevy based on preliminary clinical evidence of its effectiveness, but more data will be needed for it to remain on the market.

Such approvals are granted for medications that fulfill a significant and unmet medical need for serious diseases. They’re valid for one year and are annually renewable pending regulatory review of new clinical data. With sufficient clinical evidence, the company can eventually apply for full approval.

Ongoing studies will contribute to the body of data supporting Casgevy. Patients involved in CLIMB-121, CLIMB-111, or other previous clinical trials are continuing to be monitored for up to 15 years in the ongoing CLIMB-131 extension study (NCT04208529), which is slated to run through 2039.