FDA approves first gene replacement therapy for SMA available to all ages

FDA Approves First SMA Gene Replacement Therapy Available to All Age Groups

The FDA has approved Itvisma (onasemnogene abeparvovec-brve, Novartis), the first gene replacement therapy for spinal muscular atrophy (SMA) designed for patients over 2 years of age and adults.

This makes SMN1 gene replacement available to a wider range of older patients for the first time; previously, gene therapy was only available to children under 2 years of age.

What is Itvisma?

Itvisma contains the same active ingredient as Zolgensma, but is created in a new, highly concentrated form for single-dose intrathecal administration.

The drug is suitable for older children, adolescents, and adults, with no dose adjustment based on body weight, and delivers a functional copy of the SMN1 gene, targeting the genetic cause of SMA.

What is the basis for approval?

STEER (Phase III)

• Previously untreated patients with SMA type II

• Statistically significant improvement in motor function as measured by the HFMSE at week 52 compared with control

STRENGTH (Phase IIIb)

• Patients previously treated with nusinersen or risdiplam

• Stabilization or improvement of motor function has been confirmed.

• The tolerability profile is comparable to existing therapies.

It is estimated that approximately 9,000 patients with SMA live in the United States. The unmet need in adults and adolescents remains extremely high, primarily in the preservation of motor neurons and the maintenance of motor function.

Cost and the "Fair Price" Debate

Itvisma will launch in the US in December 2025 at a price of $2.59 million per single dose.

Novartis claims the price is 35-46% lower than the estimated 10-year cost of chronic therapy.

However, this argument raises questions.

The ICER–NEWDIGS (2024) report notes that calculating pricing based on full long-term savings to the healthcare system leads to inflated and ethically unacceptable estimates. For example, for gene therapy for hemophilia, a "fair" price based on full long-term savings would be $20–25 million.

ICER offers alternatives that only take into account a portion of the future savings:

• split the savings 50/50 between the manufacturer and the system, or

• cap the annual savings taken into account at $150,000.

By this logic, simply asserting that Itvisma's price is "lower than future chronic therapy costs" does not address the accessibility and financial sustainability of gene therapy for healthcare systems.