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Vertex teases launch plans for first CRISPR gene editing therapy ahead of FDA decision

As Vertex Therapeutics nears completion of a historic FDA submission, the rare disease specialist has depicted a rosy launch picture for what could become the first CRISPR-based gene editing therapy.

Vertex believes a network of about 50 authorized treatments centers in the U.S., and 25 in Europe, should suffice for its sickle cell disease and beta thalassemia gene therapy candidate exagamglogene autotemcel, or exa-cel, Chief Operating Officer Stuart Arbuckle told investors during a conference call Tuesday.

About 32,000 patients in the U.S. and Europe with severe disease will form the target population for the CRISPR Therapeutics-partnered exa-cel, and they are geographically concentrated, Arbuckle said. These patients require multiple hospitalizations annually for vaso-occlusive crises or are dependent on frequent blood transfusions.

Vertex and CRISPR Therapeutics started submissions of exa-cel in sickle cell disease and beta thalassemia in November 2022. The regulatory progress has moved a bit faster outside the U.S., as the European Medicines Agency and U.K. authorities have already validated the filings. In the U.S., Vertex expects to complete a rolling submission by the end of March, CEO Reshma Kewalramani said on the call.

In preparation for the launch, Vertex has established a supply chain, including buidling needed manufacturing capacity, Arbuckle noted.

Pricing has always been a sticking point for gene therapies. In the U.S., treatment costs for severe sickle cell disease patients range between $4 million and $6 million over a lifetime, Arbuckle said. Even if the companies were to price exa-cel at the lower end of that estimate, the one-time drug would break the $3.5 million drug-price record recently set by CSL’s hemophilia B gene therapy Hemgenix.

If approved, exa-cel will be the first gene editing therapy based on the Nobel-winning CRISPR technology. But it will likely have to compete with bluebird bio’s rival gene therapy lovo-cel in sickle cell disease and Zynteglo in beta thalassemia. Bluebird is pricing Zynteglo at $2.8 million and has said it will file lovo-cel for an FDA approval by March.

Before Zynteglo’s U.S. approval in August, bluebird previously retreated from the European market after failing to reach reimbursement agreements with local governments.

Hoping not to repeat bluebird’s experience, Vertex is busy talking to commercial and government payers and policymakers in the U.S. and Europe. The company aims to ensure that broad patient access and reimbursement deals are in place when exa-cel is approved, Arbuckle said.

According to Arbuckle, Vertex has talked with all U.S. state Medicaid agencies, plus about 150 U.S. commercial payers and several health economic assessment bodies in Europe, including Britain’s National Institute for Health and Care Excellence. So far, payers see exa-cel’s clinical data as “highly impactful,” especially in its ability to reduce in vaso-occlusive events and hospitalizations, he said.

Exa-cel is different from the bluebird medicines. Rather than using viral vectors to deliver a functional HBB gene, the Vertex-CRISPR therapy uses CRISPR to turn off the suppression of fetal hemoglobin and thus increase the amount of healthy hemoglobin in red blood cells.

Recent market research suggests that physicians “have a strong preference and interest in gene editing over other potentially curative approaches,” Arbuckle said, suggesting potentially better reception of exa-cel versus lovo-cel.

Vertex is not giving any sales projections for exa-cel in 2023, citing uncertain approval dates.