In a historic move, the Food and Drug Administration approved two gene therapies to treat sickle cell disease (SCD) Friday morning.

The FDA approved Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy, which utilizes CRISPR/Cas9 technology, as well as Bluebird Bio’s Lyfgenia, a cell-based gene therapy that uses a lentiviral vector for genetic modification.

Importantly, the FDA included a black box warning label for Lyfgenia due to the risk of hematologic malignancy (blood cancer) in some patients. The agency stated that patients receiving Lyfgenia for treatment should receive lifelong monitoring for blood cancer.

The two medicines are approved to treat patients over the age of 12 who are living with SCD, which is one of the most common inherited blood disorders. This patient population totals around 16,000 Americans. 

The disease, which has symptoms like anemia, blood clots, acute chest syndrome and splenic sequestration or “pooling,” is particularly common among Black and Hispanic Americans.

Notably, Casgevy is the first FDA-approved therapy using CRISPR/Cas9 technology, marking a major step forward for medical innovation on the regulatory front.

“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, MD, Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, in a statement. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”

Watershed moment for CRISPR

The FDA’s approval provides credence to the potential that many had seen in CRISPR-based treatments over the past few years.

The domestic greenlight also came weeks after Casgevy was approved for use in the U.K., making it the first CRISPR-based treatment approved there. 

Casgevy’s regulatory success comes after a winding road of clinical studies and thorough scrutiny from experts.

During the spring, Vertex and CRISPR submitted an application for approval with the FDA.

Early last month, the FDA convened a meeting of outside experts to review Casgevy, known at the time as exa-cel. No safety or efficacy concerns were raised and there wasn’t a vote taken at the end of the meeting.

This followed previous media reporting indicating that the agency’s advisers wanted additional studies to analyze “off-target” genomic changes and other side effects from the therapy.

“Casgevy’s approval by the FDA is momentous: it is the first CRISPR-based gene-editing therapy to be approved in the U.S. As importantly, Casgevy is a first-in-class treatment that offers the potential of a one-time transformative therapy for eligible patients with sickle cell disease,” Vertex CEO Reshma Kewalramani, MD said in a statement. “I want to convey my deepest gratitude to the patients and investigators whose trust in this program paved the way for this landmark approval.”

Vertex added that nine authorized treatment centers were activated in light of Friday’s news.

Bluebird notches another approval

Like Vertex, Bluebird had its own unique path to regulatory approval.

Towards the end of 2022, the FDA lifted a clinical hold on lovo-cel, which came after the agency previously paused trials and enrollment for one year after a patient developed persistent anemia. 

Shortly before the hold was lifted, Bluebird released updated data from a Phase 1/2 study that eased safety concerns about two subjects in the sickle cell disease trial.

During the spring, Bluebird submitted an application for the therapy to be approved by the FDA. Lyfgenia received priority review from the FDA in June, though Bluebird noted that it did not receive a Rare Pediatric Disease Priority Review Voucher.

Months later, the company said the agency didn’t intend to hold an advisory committee meeting for Lyfgenia.

The approval of Lyfgenia gives Bluebird its third ex vivo gene therapy greenlit by the agency and its second approval for an inherited hemoglobin disorder.

“Bringing Lyfgenia to people living with sickle cell disease is a milestone that bluebird has been working toward for almost a decade — and one that members of the sickle cell disease community have been waiting on for much longer,” Bluebird CEO Andrew Obenshain said in a statement. “Lyfgenia has the potential to have a transformational impact for patients who currently live under the shadow of unpredictable and debilitating vaso-occlusive events.”

Following the announcement, Bluebird’s stock was trading up more than 7%.

SCD remains an area of intense interest among major drugmakers, with Novo Nordisk buying clinical-stage biotech Forma Therapeutics for $1.1 billion last year in an effort to expand its blood disorders portfolio.

For a January 2024 article on Vertex’s pain drug passing a Phase 3 test, click here.