?? With the European Union pushing forward with the Joint Clinical Assessment (JCA) under the Health Technology Assessment (HTA) Regulation, companies in the CGT space need to buckle up and start preparing early. JCA aims to streamline market access European markets, but comes with its own set of challenges and requirements, many of which manufacturers might not realize.
?? The JCA Timeline & Requirements: From 2025, all new drugs, including ATMPs, must undergo this centralized clinical evaluation. The goal? To avoid repetitive assessments across different countries, accelerating patient access to innovative therapies.?
Yet, the devil is in the details:
- Rigorous Data Submission: Companies must prepare for meticulous scrutiny of clinical data and clinical trial designs. The dossier will need to justify efficacy and safety, but the standards here aren’t necessarily the same as other markets (e.g. US FDA)
- Alignment with EU Standards: Therapies must meet unified standards that may differ from national criteria. This will demand strategic adjustments in clinical trial design and data reporting, and could throw a wrench into the works if trials are already underway but won’t read out for regulatory submission until well after Q2 2025.
?? Sigla Sciences' Insights – What You Might Be Getting Wrong:
- Assumption: "Our product will automatically be preferred if it’s highly innovative and in an area of high unmet need.” ??
- Reality: Unfortunately, this doesn't guarantee market access. “Orphan indications” aren’t the same in Europe as in the US, and the evidence bar can often be much higher in Europe. Manufacturers will need to demonstrate outcomes and cost-effectiveness evidence according to EU standards.
- Assumption: "Our current clinical data & clin dev plan will be sufficient for EU JCA." ??
- Reality: Manufacturers will often need need additional data tailored to the JCA's specific requirements, encompassing broader patient populations, longer follow-up periods, fewer surrogate endpoints, more PROMs, and potentially different comparators. For manufacturers who haven’t sought early technical advice from European regulators and HTA bodies, this could be quite painful to incorporate into studies, and might require spinning up new studies, even in disease areas with small patient populations, which will inevitably lead to extended timelines or delays.
??? Pitfalls to Avoid, particularly for US-based teams:
- Underestimating Preparation Time: Start your JCA preparation early. Late realizations could lead to delays in submission and approval. If you’re planning a Phase II study, speak to European advisors soon. If you’re planning a registrational study, speak to European advisors ASAP.
- Making Assumptions / Neglecting Payer Expectations: Engage with payers early to understand their criteria and expectations within the JCA framework. This will not necessarily be what you expect. Don’t expect that US endpoints or US cost-effectiveness frameworks will automatically be acceptable across the Atlantic.
US ???? vs European market acceptance ????: Where should I look for differences?
- Single-arm Phase 2 Studies (US) vs. Robust Comparative Data (EU): ???? In the U.S., the FDA may grant accelerated approval based on the results from single-arm Phase 2 studies, especially in areas of unmet medical need where waiting for more extensive data could delay access to critical therapies. ???? In contrast, for JCA in Europe, there's a higher emphasis on comparative data. Therapies may need to demonstrate benefit against the current standard of care through randomized controlled trials, which can complicate and lengthen the approval process for ATMPs. There could be silver linings in disease areas where no or few options exist in Europe, while in the US the comparators could be a mixed bag of compassionate use or low-evidence options, but running comparative trials will come with additional expense and time.
- Surrogate Endpoints (US) vs. "Harder" Endpoints (EU): ???? The FDA is comfortable with accepting surrogate endpoints that predict clinical benefit (e.g., PFS, ORR, MRD) for accelerated approvals, particularly in oncology. ???? Meanwhile, the European JCA might require evidence based on harder endpoints, such as overall survival (OS) or significantly improved quality of life (QoL), before granting access. This can necessitate longer trial durations and larger patient cohorts to statistically validate the clinical benefits, or the incorporation of more endpoints and collection of more data through PROMs/ePROMs and related methods.
These differences highlight the importance of strategic planning and adaptability in clinical trial design to meet specific regulatory requirements in different jurisdictions. Manufacturers must carefully navigate these distinct paths to maximize product potential for approval and market access.
?? Looking Ahead – Strategic Planning:
- Early Engagement: Collaborate with regulatory experts to align your clinical development plans with JCA expectations. In reality, planning for a European launch is an 18-24 month endeavor, although many manufacturers lack this runway and timeline ability; some have successfully executed in closer to ~10 months.
- Robust Data Collection: Design trials with the JCA in mind from the get-go. Consider additional endpoints that may be relevant. Quality of Life-related PROMs, data on patient tolerability, strong endpoints, and strong comparators may be required here where they wouldn’t be for US FDA approval. Don’t fall into a “penny wise, pound foolish” trap here by failing to invest early.
- Stakeholder Alignment: Ensure that your strategy is communicated clearly across all departments. Regulatory, clinical, market access, and commercial teams should be in lockstep. If your teams haven’t had experience in Europe, bring in some experts to educate and guide their roadmapping so that steps aren’t left out.
?? The road ahead is complex but navigable with the right strategies and understanding of the evolving landscape. Companies must pivot from traditional approaches and embrace a more holistic, data-driven pathway to ensure that their innovative therapies not only reach the market but also achieve sustainable success.
?? For more insights and detailed guidance on navigating the European Joint Clinical Assessment and its impact on ATMPs, stay connected! We have in-house expertise as well as proven partnerships with on-the-ground groups in Europe who can help you navigate all of this successfully. #CGTs #ATMPs #MarketAccess #BioPharma #Oncology
