Denmark’s Pioneering Outcomes-Based Agreement for Hemgenix Gene Therapy

by Odelle Technology

Denmark has made a significant breakthrough by becoming the first Scandinavian country to approve the routine use of Hemgenix (etranacogene dezaparvovec) for treating haemophilia B. This approval is the result of an innovative outcomes-based agreement (OBA) between CSL Behring and Amgros, Denmark’s procurement authority. The OBA ensures that payments for Hemgenix are contingent on its effectiveness, addressing long-standing concerns over the high costs and uncertain long-term efficacy of advanced therapies.

Background

Hemgenix is a gene therapy designed to treat haemophilia B by introducing a functional copy of the F9 gene. This gene therapy offers a significant advancement over traditional treatments, potentially eliminating the need for frequent infusions of Factor IX (FIX) replacement therapies. However, its high cost and uncertainties about long-term effects have posed challenges for widespread adoption.

In November 2023, the Danish Medicines Council (DMC) initially decided not to recommend Hemgenix for reimbursement due to concerns about its long-term safety, efficacy, and the high cost of DKK 21.5 million (€2.9 million). The council called for a better offer, leading to the negotiation of the OBA.

Key Players

Government Representatives

Birgitte Klindt Poulsen, Vice Chairman of the DMC, played a crucial role in advocating for an agreement that balanced innovation with economic sustainability.

Representatives from Amgros, Denmark’s procurement authority, were instrumental in negotiating the terms of the OBA, ensuring that the agreement would be beneficial for both patients and the healthcare system.

The Agreement

Conditional Payment

Payments for Hemgenix are directly tied to its clinical effectiveness. Hospitals are required to pay for the therapy only if it demonstrates the expected therapeutic benefits. This ensures that financial expenditure is justified by tangible health improvements in patients. If the therapy fails to meet the predefined outcomes, the financial responsibility may be adjusted accordingly, reducing the risk for healthcare providers and payers.

Instalment Payments

Payments for Hemgenix are structured in instalments, contingent on achieving specific, predefined clinical outcomes. This phased approach allows for continuous assessment of the therapy’s effectiveness over time. For instance, initial payments might be made upon administration of the therapy, with subsequent payments following at regular intervals if the patient continues to meet health improvement benchmarks. This model incentivizes continuous monitoring and ensures that payments are closely aligned with patient outcomes.

Data Collection

Comprehensive and systematic data collection is essential to monitor the therapy’s effectiveness. This includes tracking critical metrics such as

Annualized bleed rate (ABR)

Factor IX activity levels

Occurrence and severity of any adverse events

The agreement will include detailed methodologies for data collection, ensuring that the process is well-documented and transparent. This documentation will outline who is responsible for collecting, managing, and analysing the data.

Risk Sharing

The agreement delineates the distribution of risk among the involved parties. CSL Behring and the healthcare providers share the responsibility for various potential issues, including the development and financing of the data collection model. The agreement specifies who bears the financial risk if the therapy does not meet its intended outcomes or if there are unforeseen complications. This risk-sharing model helps mitigate the financial burden on any single party and promotes a collaborative approach to managing the therapy’s implementation.

Implementation and Expectations

The first patients in Denmark are expected to receive Hemgenix treatment in autumn 2024. The agreement reflects a broader trend towards managed entry agreements (MEAs) that balance the need for innovative treatments with fiscal responsibility. These agreements often involve complex data collection and clear definitions of outcomes to ensure transparency and effectiveness.

Data Collection Details

How the Agreement Will Work

Conditional Payments

Hospitals will make payments for Hemgenix only if the treatment proves to be effective. Effectiveness will be measured by predefined clinical outcomes such as a reduction in annualised bleed rates and increased Factor IX activity levels.

Instalment Payments

 Payments will be made in instalments based on the achievement of specific health milestones. This phased approach ensures that payments are linked to real-world outcomes, with initial payments possibly made at the time of treatment administration and subsequent payments based on ongoing efficacy.

Data Collection

Comprehensive data collection is a critical component of the agreement. Detailed and precise data on patient outcomes must be gathered systematically to evaluate the therapy’s effectiveness. This includes tracking clinical metrics such as the annualised bleed rate, Factor IX activity levels, and any adverse events. The data collection process must be well-documented, with clear methodologies and responsibilities outlined in the agreement. This ensures that all parties have access to reliable and accurate information to assess the therapy’s performance.

Who Will Collect the Data

Healthcare Providers

 Hospitals and healthcare providers administering Hemgenix will be responsible for collecting patient data. This includes recording clinical outcomes during regular follow-up visits and monitoring patient health over time.

CSL Behring

As the manufacturer, CSL Behring will collaborate closely with healthcare providers to ensure accurate and comprehensive data collection. They may provide tools and support to facilitate data gathering and ensure that all relevant information is captured effectively.

Data Management and Analysis

 Collected data will be centralised and analysed to assess the therapy’s performance against the predefined outcomes. This analysis will be crucial for determining the effectiveness of Hemgenix and deciding on subsequent instalment payments.

   – The agreement will specify the roles and responsibilities of each party involved in the data collection and analysis process, including the development and maintenance of data management systems.

Use of Health Registers and Manual Data Collection

 Data may be retrieved from national health registers or through manual collection methods. The agreement will detail the specific data sources and collection techniques to be used, ensuring clarity and consistency.

Ensuring Transparency and Effectiveness

Documentation and Reporting

  – Detailed documentation and regular reporting will ensure transparency in the data collection process. This includes clearly stating how data will be collected, who is responsible for each step, and how the collected data will be used to assess the therapy’s performance.

Risk Sharing

The agreement outlines who bears the risk for various potential issues, including the cost of developing the data model and collecting the data. This risk-sharing approach ensures that both CSL Behring and the healthcare providers are invested in the therapy’s success.

Conclusion

The agreement between CSL Behring and Amgros for Hemgenix is a significant step forward in the treatment of haemophilia B. It showcases Denmark’s commitment to innovative healthcare solutions while addressing economic concerns. This model may serve as a template for future agreements, promoting the adoption of advanced therapies across Europe and beyond.

By ensuring rigorous data collection and clear terms for payment based on outcomes, this agreement aims to balance the introduction of innovative gene therapies like Hemgenix with financial sustainability and clinical accountability.

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