G-BA published the procedure for the designation of combination therapies

The basis for the designation of combination partners are exclusively all sections of the summary of product characteristics (SmPC), whereby the designation does explicity not correspond to a medical-therapeutic evaluation. The G-BA divides the drugs into three different categories:

• The "determined" combinations category includes drugs whose expert information specifically names one or more active pharmaceutical ingredients that can be used in combination with the evaluated drug.
• In the case of "undetermined" combinations, the SmPC includes information of a combination therapy, but without mentioning concrete active pharmaceutical ingredients. For example, the SmPC designates active ingredient classes or groups or information in section 4.1. such as "in addition to other medicinal products for the treatment of the disease" or as "add-on therapy to standard therapy" defining the framework of a therapeutic application on which an undetermined combination is based.
• An "open" combination is assumed, if no information on a determined or undetermined combination is included in the SmPC and, in addition, no information which regularly opposes a combination therapy with the evaluated drug in the evaluated indication (e.g. contraindications or dosage information).

The conditions for all three categories of combination therapies is an overlap of the indication and the requirement of new active pharmaceutical ingredients according to Chapter 5 of the Rules of Procedure ("Verfahrensordnung") of the G-BA at the time of the justification. Combination therapies for which – patient group-related – a considerable or major added benefit has been determined in a G-BA justification according to § 35a paragraph 3 sentence 1 SGB V are excluded from the combination discount.

The designation of the combination partners is the preliminary work of the G-BA. In a second step, the combination discount of 20 % has to be applied per drug per combinatorial prescription in accordance with § 130e SGB V. It is still unclear how the combination discount will be processed between pharmaceutical manufacturers and health insurance funds. The National Association of Statutory Health Insurance Funds (Spitzenverband Bund der Krankenkassen GKV-SV) and the manufacturers' associations are still negotiating the regulations for the implementation of the combination discount until the end of October 2023.

The manufacturers' associations criticized the combination discount. They say that the approach of the G-BA is misguided, and the legal mission cannot be interpreted in this manner. The G-BA abstained from any evaluation of the content and limited itself to the simple naming of theoretical and in part medico-therapeutically senseless combinations of active pharmaceutical ingredients. An additional mandatory discount for combinations on top of the AMNOG price regulation slows down important innovative research and therapy approaches. 

We at SKC have also analyzed the justification ("Tragende Gründe") of the G-BA and found some combination therapies determined by the G-BA as unreasonable. For example, two CAR T-cell therapies like Carvykti® together with Abecma®) were determined as a combination, although these are one-time therapies that should not be combined. Accordingly, every pharmaceutical manufacturer is urgently recommended to check the effects on its own portfolio products. Statements on the present draft of Annex XIIa of the AM-RL can be submitted to the G-BA until July 26, 2023. Once the statement procedure has been completed, the process determining the combinations will be integrated into the G-BA's rules of procedure ("Verfahrensordnung"). The law does not provide a statement procedure for the amendment of the rules of procedure. Therefore, it is important to comment on the entire process right now.

At SKC, we closely monitor the statement procedure and analyze it for you. Please feel free to contact us, we are the Market Access Special Forces.

*5. chapter G-BA rules of procedure ("Verfahrensordnung"): "Drugs with new active pharmaceutical ingredients are medicinal products containing active pharmaceutical ingredients whose effects are not generally known in medical science at the time of initial authorization. A drug with new active pharmaceutical ingredients is considered to be a medicinal product with a new active pharmaceutical ingredient for as long as document protection exists for the medicinal product with the active pharmaceutical ingredient that was approved for the first time. "

Sources:

• Tragende Gründe zum Beschluss des Gemeinsamen Bundesausschusses über die Einleitung eines Stellungnahmeverfahrens zur Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage XII/Anlage XIIa – Kombinationen von Arzneimitteln mit neuen Wirkstoffen nach § 35a des Fünften Buches Sozialgesetzbuch: Ergänzung der Benennung von Kombinationen gemäß § 35a Absatz 3 Satz 4 SGB V in bereits gefassten Beschlüssen
• BPI (06/2023): Zusammenfassung 27. Fachaustausch der Herstellerverbände mit der G-BA-Geschäftsstelle
• BPI (12.7.2023): Aktuelle Stunde Kombinationsbenennungen