Following the G-BA meeting on January 18, 2024, Tibsovo (Ivosidenib) has attained a major additional benefit rating for its application as a first-line treatment in conjunction with azacitidine for acute myeloid leukemia carrying the IDH1-R132 mutation. Tibsovo now stands as the third orphan drug to receive this esteemed rating, joining the ranks of blinatumomab, which achieved the same recognition in January 2022.
In Germany, since the inception of AMNOG in 2011, novel pharmaceuticals must undergo an initial benefit assessment. In this meticulous process, IQWiG assembles a comprehensive dossier, empowering the G-BA to ascertain the product’s benefit rating, evaluating whether and to what extent a clinical advantage over existing therapies is demonstrated. The assessment outcomes are systematically classified into six levels:
- Major additional benefit – premium
- Considerable additional benefit – medium
- Minor additional benefit – parity
- Additional benefit (non-quantifiable) – parity
- No additional benefit
- Benefit less than comparator
The outcome of the benefit rating plays a pivotal role in determining the pricing potential of drugs in Germany. Attaining a premium compared to the standard of care is only feasible when a major or considerable additional benefit rating is granted, as a minor or non-quantifiable additional benefit rating only permits price parity.
Despite a notable surge in the number of drugs receiving major additional benefit ratings from IQWiG in 2022 (9%), in contrast to the preceding two years (5%), the overall count remains relatively low. This underscores the formidable challenge manufacturers face in securing this coveted rating.
Establishing clinical advantages for orphan drugs proves particularly arduous due to non-randomized, single-arm trials often lacking robust endpoints. While orphan drugs are exempt from the benefit assessment procedure and automatically receive a non-quantifiable added benefit upon regulatory approval, they must undergo assessment if the €30m annual revenue threshold is exceeded (€50m before the GKV Financial Stabilization Act).
In 2022, IQWiG meticulously evaluated all orphan drugs that had undergone the benefit assessment procedure since 2011 due to surpassing the €50m threshold. The evaluation focused on confirming the automatically granted ‘additional benefit’ rating. In over half of the cases (54%), the confirmation did not materialize, resulting in a final rating of “no additional benefit.” This was primarily attributed to the absence of an “appropriate comparator therapy.”
Tibsovo earned its major benefit rating by undergoing the regular IQWiG assessment, which included:
- A randomized controlled trial with the appropriate comparator (Ivosidenib + Standard of Care vs. placebo + Standard of Care)
- A significant improvement on a hard primary endpoint, namely overall survival
So what does this mean for manufacturers?
With the implementation of the right trial – a randomized controlled trial with the appropriate comparator and robust endpoints – orphan drugs have the potential to secure a high benefit rating and, consequently, command a premium compared to the standard of care.