Last updated: August 27th, 2025
Italy’s medicines agency (AIFA) has overhauled how it defines “innovative” therapies, introducing a 2025 framework that sharpens evidence expectations while widening the lens for rare and ultra-rare diseases. The update retains the familiar three-pillar model—therapeutic need, added benefit, and data quality—but rebalances how each is judged in real-world practice.
What Changed in AIFA’s Innovativeness Criteria?
The Italian Medicines Agency (AIFA), through Determination 699/2025, has updated the criteria for granting a drug “innovative” status. Although the three main evaluation pillars—therapeutic need, therapeutic benefit, and quality of evidence—remain unchanged, the update places greater emphasis on therapies targeting serious conditions with a moderate to low epidemiological prevalence.
AIFA now also considers new dimensions in its evaluations, including:
- Production technology of the active ingredient
- Mechanism of action
- Method of administration
- Clinical effectiveness and safety
- Impact on patient quality of life
- Implications for healthcare organizations
Flexibility for Rare and Ultra-Rare Medicines
Recognizing the unique challenges of orphan drug development, AIFA correspondingly introduced flexibilities.
For therapies targeting rare or ultra-rare conditions, AIFA signals greater pragmatism. Products addressing critical gaps can still achieve an “innovative” label even if clinical data are limited, provided the totality of evidence—mechanism, quality-of-life impact, and plausibility—supports meaningful benefit. This nuance could broaden recognition for high-value orphan assets earlier in their lifecycle. Also, quality-of-life assessments now include pain management and the ability to perform daily or work activities.
This signals AIFA’s intent to better accommodate the realities of rare disease clinical research.
End of Conditional Innovativeness
AIFA has formally omitted the “conditional innovativeness” category. Instead of a temporary designation pending further data, products will now face a binary decision—innovative or not innovative. While this simplifies labeling, it could raise the threshold for some pipeline therapies that previously relied on provisional recognition to accelerate access.
Budget Allocation and Funding
Italy’s 2025 budget earmarks roughly EUR 300 million to sustain the national fund for “conditionally innovative” drugs, but the precise alignment between this pool and the new criteria remains to be clarified. Payers and manufacturers alike are watching to see whether this funding structure adapts to a potentially larger influx of qualifying therapies.
What Do These Changes Mean for Rare Disease Access?
The revised framework may represent a “toolbox” for flexible assessment rather than a rigid checklist.
AIFA emphasized that highly prevalent diseases are naturally rewarded by market forces, while low-prevalence, high-burden conditions require regulatory support to facilitate access.
Early signs are encouraging in the July 2025 reimbursement round, only two medicines were awarded “innovative” status—both were orphan drugs, such as:
- Hemgenix (Haemophilia B)
- Voxzogo (Achondroplasia)
This outcome reinforces optimism that rare disease communities may benefit most from the new criteria.
A Step Forward for Rare Disease Access
AIFA’s 2025 reforms mark a pivotal moment in Italy’s approach to drug innovativeness. By removing conditional status and introducing flexibility for rare diseases, the agency is signaling support for orphan medicines that face unique development challenges.
The policy’s true test will be in execution, particularly how funding allocations are managed, but for rare disease patients, these early signs point toward improved access to life-changing therapies.
Discover how our team can support market access under the new criteria
FAQs on AIFA’s Innovativeness Criteria
What is AIFA’s new framework for innovativeness?
It retains three core criteria (therapeutic need, benefit, quality of evidence) but expands evaluation dimensions and emphasizes rare diseases.
What happened to conditional innovativeness?
It has been removed. Medicines are now classified as either “innovative” or “not innovative.”
Does the change benefit orphan drugs?
Yes. Orphan drugs face more flexible evidence requirements and expanded quality-of-life considerations.
Why is the EUR 300 million budget still allocated to conditional drugs?
Uncertainty remains. How these funds will be repurposed is still unclear.
What does this mean for patients?
It could accelerate access to treatments for rare and ultra-rare diseases, though practical implementation is still unfolding.