Health authorities in the U.K. on Thursday approved a new kind of medicine that uses CRISPR gene editing to treat the blood diseases sickle cell and beta thalassemia, marking it the first time a drug built with the Nobel Prize-winning technology has won regulatory clearance anywhere in the world.
The approval is a scientific milestone that comes a decade after researchers first described how CRISPR, a viral defense mechanism borrowed from bacteria, could be fashioned into “genetic scissors” to precisely alter DNA. The technology has transformed the field of genetic medicine, offering researchers and drugmakers a powerful and adaptable tool to target the roots of inherited diseases like sickle cell and beta thalassemia.
Called Casgevy, the new medicine was developed by Vertex Pharmaceuticals and CRISPR Therapeutics. It’s approved for people 12 years of age or older who have sickle cell and the recurrent pain crises that the disease can cause, or beta thalassemia severe enough to require regular blood transfusions. The clearance is limited to individuals who aren’t able to receive a stem cell transplant from a matched donor.
Vertex and CRISPR estimate about 2,000 people in the U.K. will be eligible for Casgevy, which is built from a patient’s own stem cells that are collected, edited with CRISPR in a laboratory and then reinfused. The edit allows the reinfused cells to produce a functional form of hemoglobin, the vital oxygen-carrying protein that’s damaged in sickle cell and beta thalassemia.
Clinical testing has shown that treatment can eliminate debilitating pain crises in people with sickle cell, and free people with beta thalassemia from needing chronic blood transfusions to survive. Since CRISPR edits the stem cells’ DNA, the benefit offered by Casgevy could, in theory, last for life.
“I hope this represents the first of many applications of this Nobel Prize-winning technology to benefit eligible patients with serious diseases,” said CRISPR Therapeutics CEO Samarth Kulkarni, in a statement.
One of the first companies formed to turn the gene editing technology into medicines, CRISPR Therapeutics, partnered with Vertex in 2015. The companies later expanded their collaboration, with Vertex licensing rights to lead global development and marketing of what’s now Casgevy. Vertex splits all costs and profits of Casgevy 60/40 with CRISPR Therapeutics.
The companies did not announce a price for Casgevy, which is expected to carry a price tag potentially in the millions of dollars. In the U.K., a separate government body negotiates reimbursement for new medicines.
Cost might not be the only hurdle to treatment. Casgevy requires patients to undergo a “preconditioning” chemotherapy regimen to clear out space in the bone marrow for the edited stem cells to take root. The regimen can cause a range of side effects, including painful mouth sores and the risk of infertility. While Vertex covered fertility preservation for trial participants, the company has not yet confirmed whether it will do the same in the commercial setting.
Meanwhile, older adults who have more accumulated damage from sickle cell or beta thalassemia might not be healthy enough to go through preconditioning.
The entire process of collecting stem cells, preparing Casgevy and administering the preconditioning regimen can take many months. After treatment, patients may need to spend weeks at a hospital for safety monitoring, the U.K. drug regulator, the Medicines and Healthcare products Regulatory Agency, said.
Casgevy is also under review in the U.S., where the FDA is expected to make a decision by Dec. 8, and in the European Union. All told, Vertex estimates there are 32,000 people in the U.S. and Europe who could be eligible for Casgevy.
Despite the drug’s clear benefits, Vertex may face a tough battle in marketing Casgevy, particularly in Europe. Biotechnology company Bluebird bio won an approval of a gene therapy for severe beta thalassemia in 2019, but two years later withdrew the treatment from the market after it failed to secure broad enough reimbursement of the $1.8 million medicine.
“This is where Bluebird bio struggled and ultimately opted to wind down U.K. and EU operations,” wrote Chardan analyst Geulah Livshits in a client note Thursday. “Our view has been that Vertex’s global commercial footprint and expertise make it better positioned on this front.”
The spotlight will be greater for Casgevy, too, given its position as the first CRISPR-based medicine — and first gene editing therapy more broadly — to win regulatory approval.
“The approval remains a historic milestone for gene editing as a whole, as this technology enters the commercial arena in earnest,” wrote Leerink Partners analyst Mani Foroohar in an investor note.