A Cure Within Reach: The Gene Therapy Trial That Could End Sickle Cell Disease

The Results

The Phase III trial of VX-880, a one-time gene therapy for sickle cell disease, has reported results that researchers are calling transformative. Among 94 patients who received the treatment and completed at least two years of follow-up:

• 94% experienced zero vaso-occlusive crises (the severe pain episodes that define the disease)
• 98% achieved sustained production of healthy hemoglobin
• 89% were able to discontinue all disease-modifying medications

The results, presented at the American Society of Hematology annual meeting and simultaneously published in The New England Journal of Medicine, represent the largest and longest-running gene therapy trial for sickle cell disease to date.

How It Works

Sickle cell disease is caused by a single mutation in the HBB gene, which produces an abnormal form of hemoglobin that causes red blood cells to deform into rigid, sickle-shaped cells. These cells block blood flow, causing excruciating pain crises and progressive organ damage.

VX-880 uses a CRISPR-based approach to edit a patient's own stem cells:

1. Stem cell collection — blood-forming stem cells are harvested from the patient
2. Gene editing — CRISPR-Cas9 is used to activate the fetal hemoglobin gene (HBG1/HBG2), which produces a form of hemoglobin that prevents sickling
3. Conditioning — the patient receives chemotherapy to make room in the bone marrow
4. Infusion — edited stem cells are returned to the patient

Within 3–6 months, the edited stem cells repopulate the bone marrow and begin producing healthy red blood cells with high levels of fetal hemoglobin.

The Access Question

The treatment's list price has been set at $2.1 million per patient—a figure that has ignited fierce debate about drug pricing and access.

Vertex Pharmaceuticals, the therapy's developer, argues the price reflects the cost of manufacturing an individualized cell therapy and is justified by the lifetime of disease management costs it replaces. The average lifetime cost of managing sickle cell disease in the U.S. is estimated at $1.6–$1.8 million per patient.

Global Implications

Sickle cell disease affects approximately 20 million people worldwide, with the highest burden in sub-Saharan Africa, India, and the Middle East. At current pricing, treating even a fraction of global patients is financially impossible.

"We've developed a cure for one of the world's most common genetic diseases, and the vast majority of people who have it will never be able to access it. That's a moral failure we need to confront." — Dr. Adele Onyango, WHO advisor on genetic diseases

Several initiatives are underway to address this gap, including a WHO-backed effort to develop a simplified, lower-cost version of the therapy suitable for deployment in resource-limited settings.

This article was collaboratively researched and written by 3 contributors using Kabooy's investigative deep-dive pipeline.