Gene-cell therapies in the sights of HTA: An international study has shown that the success of high-tech drugs (HTDs) is determined not only by price

Frontiers in Pharmacology published the largest international study to date on how health technology assessment (HTA) agencies make decisions on gene therapy, including CAR-T, gene therapies, and other HTMDs.

The study covered the decisions of seven leading global HTA agencies on Kymriah, Yescarta, Tecartus, Breyanzi, Carvykti, Abecma, Luxturna, Zolgensma, Libmeldy, Roctavian, Hemgenix, Casgevy, and other innovative technologies for the treatment of oncohematological and inherited diseases, approved between 2017 and 2025.

How were decisions analyzed?

The study considered not only the final verdict ("approved" / "denied"), but also interim access formats:

• limited reimbursement,

• temporary access with review,

• managed access schemes (outcome-based agreements), where reimbursement depends on achieved clinical outcomes and additional data collection.

Drug characteristics (efficacy, safety, price, uncertainty), contextual parameters (disease severity, population size, unmet need), and HTA system features (patient participation, procedural flexibility, RWE support) were assessed.

Two approaches were used: hierarchical statistical modeling and configuration analysis (fsQCA), which allowed us to identify typical combinations of conditions—"recipes for success" and "recipes for failure."

Key findings of the study

1. The final decision depends on the system, not just the drug itself.  High price and data uncertainty significantly reduce the likelihood of a positive decision—even with convincing clinical efficacy.
2. "System adaptability" and the involvement of patient organizations play a leading role. 

Countries that use:
• special regimes for innovative technologies,

• registries and RWE platforms,

• managed access schemes, are significantly more likely to provide at least conditional access to VTMPs.

      3. Two combinations of factors most often lead to positive decisions:

• Strong clinical effect + high unmet need + adequately resourced healthcare system.

• High data uncertainty + rarity of the disease + flexible HTA agency + pre-agreed reimbursement models with conditions + mandatory RWD collection.

    4. Typical "recipe for refusal":

High price + significant data uncertainty + low system adaptability.

Under such conditions, the decision is almost always negative.

"The Adaptability Gap": Why Some Countries Implement VTLP and Others Don't

The authors introduce the concept of the adaptability gap—a gap in the adaptability of healthcare systems.

The difference lies not only in funding, but also in the institutional infrastructure:

• national registries and RWE platforms,

• early access and managed access mechanisms,

• flexible regulatory procedures,

• formalized participation of patient organizations.

Without this, gene-cell therapies remain "window dressing innovations," available only in isolated cases.

Link to document: study the original source (https://drive.google.com/file/d/1ZwFiSY2ejmSFpq2ONa2w4AJ0ao7eO3JA/view?usp=sharing)