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Vertex given green light to seek US approval of CRISPR-based therapy

By the end of March, Vertex Pharmaceuticals and CRISPR Therapeutics expect to have submitted a U.S. approval application for a gene editing medicine designed to treat two rare blood disorders.

On Tuesday, the companies said the Food and Drug Administration is allowing a so-called rolling review of their medicine, named exa-cel, for the treatment of sickle cell disease and beta thalassemia. Filing is slated to begin in November, with a completed application anticipated some time in the first quarter of next year. In Europe, where Vertex and CRISPR are also seeking approval, the companies said they’re on track to file by the end of this year.

If approved, exa-cel would become the first marketed therapy based on the CRISPR gene editing technology that won a Nobel Prize in 2020. Data generated in clinical studies have so far shown that, for most patients, a one-time treatment with exa-cel significantly alleviates the symptoms and burdens of sickle cell and beta thalassemia.

“We continue to work with urgency to bring forward the first CRISPR therapy for a genetic disease, and one that holds potential to transform the lives of patients,” said Nia Tatsis, Vertex’s chief regulatory and quality officer, in a statement.

Vertex previously aimed to submit a full application by the end of 2022, wrote Brian Abrahams, an analyst at the investment firm RBC Capital Markets, in a note to clients. Still, Abrahams and his team wouldn’t expect “a few months of difference in expected filing time to be material.”

More concerning, according to the RBC team, is the potential sales outlook for exa-cel.

Several companies, including deep-pocked players like Pfizer, Novartis and Novo Nordisk, are trying to develop new medicines for sickle cell and beta thalassemia. And just last month, Massachusetts-based Bluebird bio secured FDA approval of a gene therapy — another one-time, long-lasting treatment — for patients with severe beta thalassemia who require blood transfusions. Bluebird is developing a gene therapy for sickle cell, too.

Additionally, the way exa-cel is administered could affect how many patients seek it out.

The medicine is made with a patient’s own stem cells, which are engineered and then implanted back into the bone marrow. The process requires patients be conditioned with busulfan, a chemotherapy-based regimen that can be difficult to tolerate. For example, one patient in the exa-cel clinical trial experienced bleeding in the brain that researchers attributed to this regimen.

CRISPR has said it’s exploring alternative conditioning procedures that don’t involve chemotherapy. Even so, some analysts remain skeptical. Luca Issi, an RBC analyst who covers Beam Therapeutics, another company developing a gene-editing treatment for sickle cell, believes the commercial prospects for Beam’s program would be capped by its use of busulfan conditioning.

“We remain cautious on exa-cel’s ultimate commercial opportunity given our prior [conversations with doctors and patients], at least not until the much longer term once less toxic pre-conditioning regimens can be deployed,” Abrahams wrote.

Vertex, meanwhile, has appeared more confident in exa-cel’s sales potential. Last year, the company paid CRISPR $900 million to amend their partnership so Vertex receives a greater portion of the profits should exa-cel come to market.