Gene Therapy

Key facts

Regulatory type

Biologic, licensed through a BLA under PHS Act Section 351

FDA review office

CBER Office of Therapeutic Products

First U.S. approvals

Kymriah (CAR-T), August 2017; Luxturna (in vivo), December 2017

First CRISPR-based approval

Casgevy (exagamglogene autotemcel), December 2023

Expedited program

Regenerative Medicine Advanced Therapy (RMAT) designation

What is gene therapy?

Gene therapies work in a few basic ways: adding a working copy of a gene, inactivating a gene that causes harm, or editing a gene in place. The goal is often a one-time or long-lasting treatment rather than chronic dosing.

Genetic material is usually delivered by a vector. Adeno-associated viruses (AAV) are common for delivery inside the body, while lentiviral vectors and gene editing tools such as CRISPR are used to modify a patient's cells outside the body before they are returned.

Gene therapy overlaps with cell therapy. A chimeric antigen receptor T-cell (CAR-T) therapy is a genetically modified cell therapy, and the FDA groups both on its list of approved cellular and gene therapy products.

Types of gene therapy

Gene therapies are usually grouped by where and how the genetic change is made:

• In vivo gene therapy: the vector is given directly to the patient, as with Luxturna for an inherited retinal disease and Zolgensma for spinal muscular atrophy.
• Ex vivo gene therapy: cells are collected, genetically modified in a manufacturing facility and infused back, as with CAR-T therapies and several sickle cell disease treatments.
• Gene editing: tools such as CRISPR-Cas9 change DNA at a targeted site; Casgevy was the first CRISPR-based therapy approved in the United States.
• Not included: antisense and small interfering RNA (siRNA) products also alter gene expression but are generally regulated as drugs rather than gene therapies.

Why gene therapy matters

Gene therapies strain traditional payment, access and data models:

• Pricing and payment: many gene therapies carry one-time list prices in the millions of dollars, which has driven outcomes-based agreements and installment payment models.
• Medicaid policy: the CMS Cell and Gene Therapy Access Model lets participating state Medicaid programs pay for sickle cell disease gene therapies under outcomes-based terms negotiated by CMS.
• Site of care: administration is concentrated at a limited number of qualified treatment centers, which matters for targeting and network planning.
• Long-term follow-up: FDA guidance recommends following gene therapy trial participants for years to detect delayed adverse events, which extends evidence timelines.