Masterarbeit
Assessment of potential similarity between orphan drugs
Dr. Peter Satter (2007)
Language: English
The incentives of the European orphan drug regulation attracts companies to invest in new drugs for the treatment of rare diseases. Especially the market exclusivity of 10 years for the originator against similar competitors justifies the high development costs for new orphan drugs. Therefore the term similarity has an important rule within the orphan drug regulation. The legal stipulation of similarity assessment is given in the Regulations (EC) No. 141/2000, 847/2000 and a community EC Draft Guideline from 2004.
The interpretation of this similarity definition by the competent authority can be studied in current 5 precedent decisions of the CHMP for orphan drugs in the same indications. In all cases the CHMP decided that the drugs are non-similar and a rapid market access for the competitors was possible. These decisions were in 4 out of the 5 cases in clear consent with the legal definition of similarity. The differences between the orphan drugs regarding structure and mode of action are in all cases major. But an exception is the example Glivec vs. Sprycel. Sprycel is an important treatment option for CML patients with Glivec resistance. But both drugs have a close relationship regarding the mode of action and structure. The reasons for the CHMP to assess non-similarity is based on the argument that the interconnections between the identical structural features N-phenyl-amide, piperazine ring, pyrimidin ring are different. This CHMP interpretation of structural non-similarity shows that competitors with a close structural relationship can also get market access without the obligation to show first clinical superiority. This is in the case of Sprycel acceptable as the drug offers an important treatment option. But the decision shows also the disadvantage of the actual guideline. The rules of similarity contain too many exceptions and caveats for the similarity decision. Therefore smart copies without an additional use for the patient can also get a fast approval.
In order to protect the interests of the industry and to avoid the erosion of the term market exclusivity an important industry organisation (Emerging Biopharmaceuticals Enterprises - EBE) developed an alternative model to assess similarity. In opposite to the current EC Draft Guideline is the definition of similarity very strict. The intention of this model is to have only new innovative orphan drugs or competitive drugs with shown clinical superiority on the market. A comparison of the EBE proposal with the actual CHMP decisions showed that in most cases also an assessment of non-similarity would be given. But a completely different assessment by the EBE proposal would be given for Glivec vs Sprycel. As both drugs have the same INN substem and same mode of action the clinical superiority for Sprycel has to be shown before an approval can be given. The EBE proposal is a reasonable model which supports also the rapid access of innovative orphan drugs. But the model shows also with the example Glivec vs Sprycel one of its main disadvantages. On the one site it protects innovative drugs against smart copies but it also inhibits on the other site the rapid access of needed drugs.
Based on current experience with the assessment of similarity a review of the EC Draft Guideline is needed. The review discussion shall include all aspects get from the current experience with the guideline. Therefore ideas like the EBE model and for the optimisation of the procedure (stronger focus on the structure, integration of subsets of indications, including of the COMP, decision regarding similarity in an early development stage) should be discussed. Based on this review an assessment procedure should be developed which supports the interests of the patients and industry.
Pages: 29