Bluebird, Vertex ready for debut of sickle cell gene therapies

Last week, physicians at Children's National Hospital in Washington, D.C., collected stem cells from a young boy suffering from sickle cell disease, setting the stage for the first commercial use of a newly FDA-approved gene therapy by Bluebird Bio. This treatment, known as Lyfgenia, aims to counter the defective hemoglobin protein that characterizes the blood disease. The process involves extracting the patient’s own stem cells, modifying them to carry a functional gene, and then reintroducing these cells back into the patient. Bluebird estimates that the entire procedure, from cell extraction to re-infusion, takes between 70 and 105 days.

This recent cell collection, reported by The New York Times, represents a significant milestone in the management of sickle cell disease. Sickle cell disease, the first genetic disorder identified at the molecular level, results from mutations in the hemoglobin protein, causing red blood cells to assume a sickle shape and obstruct blood vessels. These blockages can lead to severe pain and long-term organ damage.

Despite the early identification of the molecular cause, effective treatments have remained elusive for decades. Hydroxyurea, a cancer drug repurposed for sickle cell, is commonly used but not universally effective. Newer medications offer limited benefits, and stem cell transplants, while potentially curative, face challenges such as finding suitable donors and significant procedural risks.

Lyfgenia is one of two gene therapies offering hope for a near cure. The other therapy, Casgevy, also received FDA approval in December and is notable for its use of CRISPR gene-editing technology. On the same day Lyfgenia’s cell collection was reported, Vertex Pharmaceuticals announced that five patients had initiated cell collection for Casgevy treatment, which is also approved for severe beta thalassemia. These collections occurred across the U.S., Europe, and the Middle East.

Stuart Arbuckle, Vertex’s chief commercial officer, highlighted the rapid progress and the complexities involved in the patient treatment journey during a conference call with investors and analysts. However, both therapies come with hefty price tags. Bluebird Bio has priced Lyfgenia at $3.1 million, whereas Vertex and CRISPR Therapeutics have set Casgevy’s price at $2.2 million. The high costs have raised concerns regarding patient access and the financial strain on Medicaid, which covers many of the estimated 20,000 sickle cell patients in the U.S. For the young boy set to receive Lyfgenia, his insurance will cover the treatment costs.

Both Bluebird and Vertex are considering outcomes-based contracts to link payment to treatment success. Additionally, the federal government is coordinating efforts to streamline Medicaid coverage across states. Despite this progress, several challenges remain. The manufacturing processes for both Lyfgenia and Casgevy are complex and time-consuming. Patients are required to undergo cell collection, which might need repetition, and endure preconditioning chemotherapy to ensure proper engraftment of the engineered stem cells. This chemotherapy carries risks, including potential infertility, which may deter some patients.

Hospitals face their own challenges in administering these therapies. Facilities need to establish comprehensive care teams and supportive services. Bluebird Bio has certified more than 60 centers for administering Lyfgenia, while Vertex has prepared 25 centers for Casgevy across approved regions, with a global target of 75 centers.

In conclusion, the advancements in gene therapy for sickle cell disease, particularly through Lyfgenia and Casgevy, represent a promising leap forward. However, the associated costs, logistical complexities, and patient risks present significant hurdles that need addressing to ensure broader accessibility and success of these groundbreaking treatments.