Key Decisions on Health Technology Assessment at ACP124: Implications for Rare Disease Therapies

Health technology assessment (HTA) plays a crucial role in determining whether new therapies are reimbursed within healthcare systems. At the July 18, 2025 meeting of the Adviescommissie Pakket (ACP), two high-profile orphan drugs—omaveloxolone (Skyclarys®) for Friedreich’s ataxia and exagamglogene autotemcel (exa-cel/Casgevy®) for transfusion-dependent β-thalassemia—were evaluated for reimbursement. How do decision-makers balance innovative treatments against budget impact and cost-effectiveness thresholds? This summary addresses how health technology assessment guides such pivotal outcomes, directly impacting patient access and healthcare sustainability.

Key Findings from the ACP124 Meeting

The Adviescommissie Pakket meeting (linked below) spotlighted health technology assessment as pivotal for managing high-cost, rare disease therapies. Both therapies reviewed exemplified the challenges in assessing value and affordability:

• Omaveloxolone (Skyclarys®): Evaluated as a clinically meaningful therapy for Friedreich’s ataxia, it offers modest slowing of disease progression but fails to meet cost-effectiveness thresholds at its current annual cost of €245,572 per patient. The incremental cost-effectiveness ratio (ICER) stands at €1.94 million per QALY, requiring an 84% price reduction to align with the Dutch reference threshold of €80,000 per QALY.
• Exagamglogene autotemcel (exa-cel/Casgevy®): This one-time gene therapy enables over 90% transfusion independence for β-thalassemia patients. However, its per-patient price of €1.9 million generates an ICER above €167,000 per QALY. Achieving cost-effectiveness would require at least a 43% price reduction.

Overarching HTA Insights

• Uncertainty: Both interventions face high uncertainty in long-term benefits and potential eligible patient numbers.
• Centralized Implementation: Protocol-driven, centralized treatments and systematic data collection are strongly recommended to optimize patient outcomes and facilitate future value assessments.
• Policy Tools: The use of pay-for-performance agreements and budget caps is increasing, aiming to control costs in the presence of uncertain outcomes.
• Alignment with Global HTA Trends: There is a continued shift towards integrating real-world evidence, patient-centered outcomes, and sustainable reimbursement models.

These elements highlight a broader evolution within international health technology assessment, where cost utility, innovation, and patient experience are balanced against system affordability.

Context: Orphan Drugs and HTA Policy

Orphan drugs target rare, severe diseases but frequently come with high costs and limited supporting data. There are ongoing challenges in demonstrating favorable cost-effectiveness for these interventions, despite urgent clinical needs.

• Friedreich’s ataxia: Characterized by significant loss of independence, with mFARS and activities of daily living indices used for outcome measurement, yet progression over short trial periods tends to be slow and heterogeneous.
• Transfusion-dependent β-thalassemia: Patients endure lifelong transfusions, organ complications, and increased mortality risk. While gene therapies show promise for transformative impact, long-term real-world evidence remains limited.

HTA agencies globally are increasingly relying on conditional reimbursement models to strike a balance between rapid access and robust post-market evidence requirements.

Implications for Health Economics and Future Assessments

How Are Value-Based Judgements Made in Dutch HTA?

• Quantifying Disease Burden: The Dutch HTA framework relies on explicit criteria—proportional shortfall, QALY loss, and societal perspective (including informal care and productivity impact).
• Cost-Effectiveness and Price Negotiation: Therapies exceeding cost per QALY thresholds are typically subject to price negotiations or managed entry agreements, linking the notion of system sustainability with health technology assessment.
• Evolving Methodology: The integration of real-world data and patient-reported outcomes will become increasingly important for future HTAs, especially for therapies with high up-front costs and uncertain long-term value.
• Risk-Sharing Agreements: Managed entry agreements—such as pay-for-performance, budget caps, and treatment registries—are standardizing to address uncertainty and support responsible access.

Learn more about the committee’s deliberations, recommendations, and policy context in this detailed ACP124 analysis by Zorginstituut Nederland.

Frequently Asked Questions (FAQ)

How does health technology assessment determine if a drug is reimbursed in the Netherlands?
Health technology assessment evaluates therapies based on clinical benefit, disease burden, QALY-based cost-effectiveness, budget impact, and broader societal value. If a drug’s cost per QALY exceeds national thresholds (€80,000 for high disease burden, €50,000 for moderate), it may require price renegotiation or alternative access agreements.

What options exist when a treatment is not initially cost-effective but meets high unmet need?
Conditional reimbursement arrangements, such as pay-for-performance contracts and price-volume agreements, may provide temporary access while additional evidence is collected or prices are adjusted. Patient perspectives and societal impact are considered but rarely override the necessity for proportional long-term value.

Why is centralized treatment and ongoing data collection emphasized for rare disease therapies?
Centralizing care in specialized centers ensures highest standards, optimizes patient selection, and facilitates robust long-term data collection. This is critical for reducing uncertainty and enabling more informed future health technology assessments, particularly for new and expensive treatments.

Conclusion and Further Reading

Health technology assessment remains at the forefront of evidence-based reimbursement in the Netherlands. The ACP124 meeting underscored the importance of linking therapy price to societal value and highlighted the necessity of robust real-world data, especially for orphan drug evaluations. For further context on HTA policy and to explore related topics such as conditional access agreements, cost utility analysis, and advancements in patient-centered measurement, refer to the official ACP124 documentation and agenda.