Concerns raised by ARM over EU HTA guidance impacting ATMPs and rare diseases

ARM has expressed concerns about the potential impact the EU HTA Coordination Group’s recent guidance may have on advanced therapy medicinal products (ATMP) and rare diseases.

The Alliance for Regenerative Medicine (ARM) has responded to the EU Health Technology Assessment (HTA) Coordination Group‘s recent publication of the ‘Methodological Guideline for Quantitative Evidence Synthesis: Direct and Indirect Comparisons‘. ARM has expressed concerns about the potential impact of the guideline on rare disease patients and the ATMP sector.

ARM asserts that the Joint Clinical Assessment (JCA) aimed to streamline the clinical assessment step in HTA, reducing duplication across EU Member States and potentially accelerating patient access to ATMPs. However, ARM argues that the guideline overlooks the HTA Regulation’s directive to adopt fit-for-purpose methodologies for ATMPs. They contend that the guideline’s insistence on randomized controlled trials (RCTs), even when not feasible, could pose a hindrance to this goal.

Carla Vossen, Syneos Health, acknowledged that using RCTs for rare diseases may not always be ethical or feasible, stating,

“It is well known that  RCTs are the ‘gold standard’ to determine efficacy and safety information leading to marketing authorization or reimbursement approval. However, for rare diseases, it might not be ethical or feasible to conduct RCTs, and manufacturers then often perform single-arm trials (SATs). External control arms (ECAs) are used to contextualize the results from these SATs.”

According to ARM, the guideline’s similarity to the initial draft and its stance on the sufficiency of single-arm or non-randomized evidence raise concerns. They highlight the argument that SATs are sometimes necessary for ethical, scientific, and practical reasons, particularly in evaluating rare disease treatments. They suggest that such trials, informed by real-world data like disease registries, can adequately demonstrate clinical benefit.

ARM warns that the guideline’s approach may lead to inconclusive JCA reports for many ATMPs, potentially delaying patient access and undermining the implementation of the EU HTA Regulation. They express concern about the potential negative impact on the EU’s competitiveness in the ATMP sector, especially for smaller biotechnology companies, and fear that rare disease patients could face fewer treatment options in the EU as a result. They advocate for a more flexible approach to clinical assessment methodologies, particularly considering the unique challenges posed by rare diseases.

Jasdeep Hayre, NICE, underlined this, saying,

“In rare diseases, especially ultra-rare diseases where the number of affected individuals can be in single digits in some jurisdictions…sometimes a SAT is the only approach that can be taken, so it’s incumbent on the regulator and HTA agency like NICE to take these specific circumstances into consideration. We mustn’t lose sight of the aim of enabling access to new cost-effective treatments and technologies, which is of course our main aim.”