Nine European Countries, Divergent Verdicts: How Health Technology Assessment Shapes Access to Advanced Therapies

A cross-country review of Europe’s most innovative medicines has revealed striking inconsistencies in how national health technology assessment (HTA) bodies judge the same therapies, and how often reimbursement is granted even when official recommendations are negative. The study, published in Discover Health Systems, examined the HTA evaluations and reimbursement status of all advanced therapy medicinal products (ATMPs) holding an active European marketing authorization as of 31 March 2026 across England, Scotland, France, Germany, Italy, Spain, Ireland, Denmark and Sweden. Its central finding is that only a small fraction of licensed ATMPs has been formally appraised in all nine countries, and that no single therapy received a positive recommendation from every HTA body assessed.

ATMPs are medicines for human use based on genes, tissues or cells. The category comprises three main types: gene therapies, which modify or manipulate genes, introduce new genes or regulate gene expression to treat disease; cell therapies, which use living cells to repair, replace or enhance biological function; and tissue-engineered products, which use engineered cells or tissues to repair, regenerate or replace damaged tissue. These treatments are often potentially curative options for severe diseases where no other treatments exist, which makes the patchiness of their evaluation and reimbursement across Europe particularly consequential for patients.

The researchers assessed all ATMPs with an active European Medicines Agency marketing authorization by March 2026, drawing on the official websites of the national HTA bodies and supplementing these searches with grey literature, including published positive lists of medicines, to verify reimbursement status. Therapies whose marketing authorization had lapsed or been withdrawn were excluded, as were products such as Chondrocelect, Glybera, MACI, Provenge, Zalmoxis, Zynteglo, Skysona and Alofisel. For multi-indication therapies such as Yescarta, Kymriah, Tecartus and Casgevy, the specific indication under review was recorded. Because Sweden’s TLV publishes health economic assessments without a recommended-or-not outcome for hospital-dispensed medicines, the Swedish results were reported as cost per QALY, with the New Therapies council handling pricing negotiations and the eventual reimbursement decision.

At the time of the research, 22 ATMPs held active EU marketing authorizations, 20 of which had received orphan designation. Eighteen of the 22 were gene therapy medicinal products, with two tissue-engineered products and two cell therapies. Yet only six of the 22—Yescarta, Kymriah, Zolgensma, Luxturna, Tecartus and Libmeldy—had either undergone HTA evaluation or been considered for evaluation with an incomplete manufacturer submission across all nine HTA bodies in scope. None of the reviewed ATMPs gained positive recommendations from all nine bodies, either because of negative evaluations or because the treatments had not been assessed at all.

The pattern of positive recommendations varied sharply by agency. AIFA in Italy issued 15 positive opinions out of 16 evaluations, Germany’s G-BA gave 13 out of 16, and England’s NICE 15 out of 18, making these three the most favorable assessors. At the other extreme, Ireland’s NCPE did not recommend any of the eight ATMPs it assessed for reimbursement. NCPE had also assessed the fewest products, leaving 14 of the 22 approved ATMPs unassessed, while Sweden’s TLV had not assessed 11, Denmark’s DMC 10 and Scotland’s SMC 9. Among TLV’s assessments, 6 of the 11 ATMP reports indicated a cost per QALY within the agency’s accepted threshold range of SEK 500,000 to 1 million.

Some individual products fared notably well despite the overall fragmentation. Holoclar, one of the first ATMPs to gain European marketing authorization, was evaluated by five of the nine agencies—NICE, SMC, AIFA, HAS and AEMPS—with all reports recommending the treatment for full or restricted use. Upstaza and Hemgenix received positive evaluations from seven of the HTA bodies, while Tecartus and Casgevy received positive evaluations from six. Imlygic was evaluated in five countries but recommended for full or restricted use only by NICE and the G-BA, receiving negative recommendations from SMC, AEMPS and NCPE. Spherox had been assessed by three agencies, gaining a partial recommendation from NICE, a recommendation from AIFA and a negative one from HAS. The remaining products—Abecma, Breyanzi, Carvykti, Roctavian, Ebvallo, Vyjuvek, Aucatzyl and Zemcelpro—had five or fewer positive recommendations.

Reimbursement outcomes did not always track HTA verdicts. Yescarta, Kymriah and Luxturna secured reimbursement in all nine countries for the indications under review, even where national HTA bodies had issued negative recommendations. In Ireland, Yescarta, Kymriah, Luxturna, Zolgensma, Tecartus and Carvykti were eventually reimbursed by the Health Service Executive after financial agreements despite negative NCPE recommendations. Libmeldy is reimbursed in all countries except Spain, where it received a negative IPT, and Tecartus is reimbursed everywhere except Denmark after a negative DMC recommendation. In Spain, positive Therapeutic Positioning Reports for Upstaza and Roctavian did not translate into inclusion on the official reimbursement list, which the authors attribute to possible delays in price negotiations and the non-binding nature of these reports on reimbursement decisions.

The countries with the highest number of positive HTA outcomes—Germany, Italy and England—also reimburse the most ATMPs, with 16 in Germany and 15 each in Italy and England out of the 22 approved products. By contrast, Sweden and Ireland offer access to fewer therapies, reimbursing 8 and 7 out of 18 ATMPs respectively. The authors link these differences to national structures: Germany’s free pricing during the first six months after launch and its orphan-drug process allowing coverage without demonstrated benefit below €30 million in annual sales, with most ATMPs receiving a non-quantifiable additional benefit rating; and Italy’s innovative-status scheme, which grants access to a dedicated fund, immediate addition to regional formularies and exemption from payback schemes. Specialized pathways also matter in England and Scotland, where ultra-rare routes apply higher cost-effectiveness thresholds—NICE’s highly specialised technologies pathway starts at £100,000 per QALY and can rise to £300,000—and allow outcomes-based agreements and temporary reimbursement with registry-based evidence generation.

Countries without such specialized pathways—Ireland, Sweden and Denmark—tend to show lower rates of reimbursed ATMPs, a trend the authors interpret as pointing to the limitations of standard cost-effectiveness assessment for early innovative technologies. Collaborative European initiatives offer a partial workaround: Libmeldy was the only ATMP evaluated by both FINOSE and BeNeLuxA, with joint clinical assessment followed by national negotiations leading to reimbursement in Sweden and Finland and, through BeNeLuxA, across all involved countries, including Ireland, where the joint process overturned NCPE’s negative recommendation. Zolgensma likewise underwent BeNeLuxA evaluation, producing a joint pricing and reimbursement agreement for two defined subgroups of young patients in Belgium, Ireland and the Netherlands. The EU Joint Clinical Assessment framework under Regulation (EU) 2021/2282, applicable since January 2025, now subjects new oncology treatments and ATMPs to a centralized clinical assessment using a standardized PICO framework, producing a single EU-level clinical evidence report that national bodies use for their own economic evaluations—though whether this will yield more consistent reimbursement outcomes remains to be seen, as pricing and reimbursement decisions continue to rest with national authorities.

The study has limitations the authors acknowledge: it reflects data available as of 31 March 2026 and excludes subsequent HTA updates or market changes; it relied on official HTA websites and grey literature, which may vary in completeness or accessibility; and it did not assess the criteria used in HTA decision-making. Within those bounds, the conclusions are clear. Several ATMPs with active EU marketing authorization had not yet undergone formal HTA evaluation across all nine countries, with gaps for recently authorized therapies reflecting expected administrative timelines, but persistent evaluation gaps in Ireland, Denmark and Sweden suggesting deeper structural challenges. Zemcelpro, at the time of the study, was not reimbursed in any of the countries in scope, while Breyanzi, Carvykti and Hemgenix were reimbursed in six of nine. The authors conclude that harmonized and transparent review processes adapted to the specificities of ATMPs are needed, and that the three therapies reimbursed everywhere demonstrate that access is possible even without uniformly positive HTA outcomes, through payer flexibility, specialized evaluation routes and post-assessment negotiations.

Subject of Research: Cross-country variation in health technology assessment recommendations and reimbursement of advanced therapy medicinal products in nine European countries

Article Title: Variation in Health Technology Assessment recommendations and reimbursement of Advanced Therapy Medicinal Products across nine european countries

Article References: Georgiou, P. M., & Athanasakis, K. P. (2026). Variation in Health Technology Assessment recommendations and reimbursement of Advanced Therapy Medicinal Products across nine european countries. Discover Health Systems, 5(1), Article 73. https://doi.org/10.1007/s44250-026-00416-w

Image Credits: AI Generated

DOI: 10.1007/s44250-026-00416-w

Keywords: advanced therapy medicinal products, health technology assessment, reimbursement, gene therapy, orphan drugs, Europe, NICE, patient access, cost-effectiveness, managed entry agreements, EU Joint Clinical Assessment, rare diseases