Italy redefines innovativeness: new criteria and the end of “conditional” status may signal positive news for the rare disease community
The revised criteria shift focus to consider new dimensions
In July 2025, the Italian Medicines Agency (AIFA), via Determination 699/2025, renewed the criteria for awarding “innovative” status to drugs. While the three key criteria (therapeutic need, therapeutic benefit, and quality of evidence) remain the same, the focus shifted as the criteria apply to treatments for serious diseases with moderate-to-low epidemiological impact.
The drug’s assessment now considers new dimensions such as production technology of its active ingredient, mechanism of action, method of administration, clinical effectiveness and safety, quality of life impact, and implications for healthcare organisation.
The Determination recognises flexibilities for rare and ultra-rare drugs. Orphan drugs can qualify for innovativeness even if quality of evidence is 'Low' (at least 'Moderate' quality is generally required) and the quality-of-life assessment can also include pain and ability to perform common or work-related activities.
The end of ‘conditional innovativeness’ leaves questions about its impact and the allocation of funds
The AIFA Determination no longer references “conditionally innovative” drugs for access to the Innovative Medicines Fund, leading readers to think that drugs will either be classified as ‘innovative’ or ‘not innovative’. AIFA’s technical-scientific director noted that conditional innovativeness “may have been suitable with clinical trials of 15 years ago, where the medicine was admitted for reimbursement, the development plan was completed in the post-authorisation phase, and new evidence would complete or modify the conditions for access to the medicine. Today, this almost never happens”.
Despite this, the 2025 Budget Law allocates up to EUR 300 million per year for “conditionally innovative” drugs, causing speculation on how these funds will be used.
What might these changes mean for access to rare disease drugs?
The updated innovativeness criteria may be considered as a “toolbox” for flexible assessment. While the definition of “serious diseases with medium-low epidemiological impact” may appear vague, AIFA’s technical-scientific director noted that “the intent of the legislator was to express a principle of a general nature: an innovative medicine aimed at treating a disease with high prevalence will be rewarded by the market; it does not need an incentive to facilitate access”.
Orphan drugs may benefit from the stronger focus on low-prevalence diseases. While it is early to judge the impact of the new ‘innovative/not innovative’ classification for orphan medicines, the July 2025 reimbursement round offers encouraging signs. Out of eleven drugs approved, the only two drugs which received “innovative” status were orphan drugs: Hemgenix for Haemophilia B and Voxzogo for achondroplasia.
Next steps…
Our Decisive Consulting team will continue to track AIFA’s developments and guide our network through the new criteria and their significance for the rare disease community.
Contact enquiries@decisiveconsulting.co.uk for more information.
References
https://www.quotidianosanita.it/scienza-e-farmaci/articolo.php?articolo_id=131268
https://www.quotidianosanita.it/allegati/allegato1752498628.pdf
Written by Gaia Geraci
Decisive Dialogue 27th August 2025