Vertex and CRISPR Therapeutics have scored authorization in the U.K. for their exa-cel gene therapy to treat patients with severe forms of sickle cell and transfusion-dependent beta thalassemia, two genetic disorders of the blood.
It is the first ever endorsement for a CRISPR-based gene editing treatment. Three years ago, the developers of CRISPR won a Nobel Prize for discovering the groundbreaking platform. Analysts at Leerink Partners called the nod an “historic milestone for gene editing.”
Despite the excitement for the anxiously awaited drug—which Vertex said will potentially open the treatment up to 2,000 patients in the U.K.—a key question remains: Because of its steep price, will it ever be commercialized in England?
Four years after gaining approval in the United States for its game-changing cystic fibrosis treatment Trikafta, Vertex has yet to win over regulators in Britain. Early this month, the U.K.’s National Institute for Health and Care Excellence (NICE) revealed draft guidance that recognized the effectiveness of Trikafta—which is known as Kaftrio in Europe—but stopped short of labeling it cost-effective. Its price tag in the U.S. is roughly $326,000 annually.
Without revealing what it will charge for exa-cel—which has been dubbed Casgevy in Europe—Vertex said it is “already working closely with national health authorities to secure access for eligible patients as quickly as possible.”
Vertex knows the drill. Several years of wrangling between the company and U.K. regulators never amounted to a marketing authorization for another of Vertex’s cystic fibrosis drugs, Orkambi, which was approved in the U.S. in 2015.
As a single-use gene therapy, expect Casgevy’s price to exceed $1 million. Bluebird, which has two approved gene therapies on the market in the U.S., pulled up stakes in Europe when it could not agree to a cost-effective price with regulators. The company called the pricing situation “untenable” and referred to the market as “broken.”
Thursday’s U.K. authorization—which endorses Casgevy’s safety, quality and effectiveness—is to treat patients 12 and older.
Early this month, an FDA advisory committee signed off on exa-cel, tamping down concerns about off-target effects. The thumbs-up paves the way for the FDA to green light the treatment. The regulator has established decision dates of Dec. 8 for the sickle-cell application and March 30 for beta thalassemia.
During Vertex’s third-quarter conference call last week, chief operating officer Stuart Arbuckle called exa-cel a “multibillion-dollar” opportunity, with 2024 being a foundational year as the company sets up treatment centers and readies patients for the therapy.
Bone marrow stem cells are taken from patients and CRISPR is used to modify the marrow before they are reinfused. The treatment allows the production of fetal hemoglobin (HbF), replacing the defective hemoglobin of people with the diseases.
The endorsement is based on results from two trials that showed sickle cell and beta thalassemia patients who received exa-cel did not have vaso-occlusive crises and had become transfusion independent for at least 12 months. The benefits are expected to be life-long, the companies said.
Exa-cel is the result of a 2015 collaboration between Vertex and CRISPR Therapeutics. CRISPR CEO Samarth Kulkarni said that he hopes the authorization “represents the first of many applications” of CRISPR technology.
“Today is a historic day in science and medicine,” Reshma Kewalramani, M.D., CEO of Vertex, said in a release.