| dc.description.abstract | Rare diseases are diseases which have a low prevalence and are mostly life-threatening or seriously debilitating. It is estimated that more than 55 million people in Europe and the United States of America together are affected by one of the 5,000 to 8,000 different known rare indications. For many of these rare diseases no adequate treatments have come available. This lack of adequate treatments is explained by the fact that orphan drugs are unsuccessful pharmaceutical innovations due to the low estimated economic profitability. Sponsors are therefore not interested in developing a treatment for these diseases. Finding effective and safe treatments for patients suffering from rare diseases is therefore an important public health issue. Consequently, and to encourage pharmaceutical innovations for orphan diseases, different orphan legislations were implemented.
Despite these orphan legislations, for many rare diseases no effective and safe treatments are available yet. At the same time, some orphan diseases are associated with a high number of orphan medicinal products (OMP’s). More detailed, for some rare indications with an authorized OMP on the market, other follow-on OMP’s (FOMP’s) are in development or sometimes even authorized. This implies a (skewed) distribution for orphan drug development and more specific, for FOMP development. As a result, part of the patients suffering from an orphan disease never get access to better, and finally optimal, treatments for their rare disease, despite the fact that the legislations were aimed at giving patients of rare diseases access to treatments having the same quality as other patients. This thesis therefore aimed to elucidate this (skewed) distribution. On the one hand, this thesis aimed to identify the factors explaining FOMP development and, on the other hand, to characterize the sponsors of FOMP’s in development. This resulted in the following main research question to be answered within this thesis: which factors explain the development of FOMP’s and how can the sponsors of FOMP’s be characterized?
Van Noordwijk (1984) identified three prerequisites complying to a successful pharmaceutical innovation, namely economic profitability, technological feasibility and medical need. More detailed, this framework gives insight in a diverse range of aspects involved in drug development and was therefore used in this thesis to examine factors explaining the development of FOMP’s. However, this thesis adapted the prerequisites of Van Noordwijk (1984) to get broader characteristics that better fit to orphan drug development. As a result, this thesis investigated the following characteristics: product-related (technological feasibility), market-related (economic profitability) and disease-related (medical need) characteristics. A comparison between rare indications with an approved OMP and at least one FOMP and rare indications with an approved OMP and no FOMP was performed to identify possible factors explaining FOMP development. Thereafter, the characterization of the sponsors of FOMP’s was examined by describing some business-related characteristics of the sponsors and by describing to what extent, and for what reason, sponsors of FOMP’s are characterized by a positive decision to continue further development after market authorization of the first OMP for a particular rare disease. As a matter of fact, sponsors of FOMP’s are not able to fully benefit from the main innovation encouraging market exclusivity instrument. In addition, the concept of significant benefit was used to investigate the reason for the decision of FOMP sponsors, since FOMP sponsors have to show significant benefit to obtain a market approval. This thesis performed descriptive statistics for the characterization of FOMP sponsors. Finally, all data in this thesis was collected from sources in the public domain only. Moreover, this thesis was mainly focused on Europe, however, some additional analyses were done for an US sample.
The development of at least one FOMP was strongly associated with the disease prevalence (market size) of the rare indication (odds ratio: 25.2; confidence interval: 2.5-259.2). In addition, from the US sample the disease class (oncology) was observed as second predictor for FOMP development. FOMP sponsors, and especially authorized FOMP sponsors, were characterized by a high percentage (46.4 %) of large-sized firms. Furthermore, most (53.3 %) FOMP sponsors had at least two other orphan designations (OD’s). In addition, all sponsors – except for one – decided to continue further development after market authorization of the first OMP for the same rare indication. Moreover, this thesis observed that termination of FOMP development was mostly related to conducting clinical trials, focus on another more promising indication of the same OMP, registration failure and the lack of funding. Finally, the findings showed that almost all (93.3 %) FOMP sponsors expect to demonstrate an improved efficacy compared to the first approved OMP for the same rare indication.
This thesis showed that the market size (disease prevalence) of a rare indication is an important predictor for the development of at least one FOMP for rare diseases with an authorized OMP. In addition, in the US sample, the disease class was found as second predictor for the development of at least one FOMP for rare indications with an authorized OMP. FOMP sponsors, and even more the sponsors of authorized FOMP’s, are characterized by a high percentage of experienced and large-sized firms. Further characterization of FOMP development reveals a strong preference by large-sized sponsors for orphan drug development for rare diseases having a prevalence above 1 per 100,000 and oncologic disorders. Finally, the sponsors appear to be satisfied with a shared market exclusivity due to their positive decision regarding further development after market approval of the first OMP for the same rare indication. As a result, the instrument of market exclusivity does not create a disincentive for other companies to invest in rare diseases having an approved OMP. More general, from our results it is concluded that an instrument, aimed at encouraging pharma innovation for unmet medical needs, does not contribute to the lock-in of one particularly technology (i.e. an authorized OMP). In addition, almost all of the FOMP sponsors expect to justify significant benefit by showing an improved efficacy profile compared to the first approved OMP.
The aim of this research was to further elucidate the observed (skewed) distribution of OMP’s. It is concluded that there is a skewed distribution for the translation of rare disease research into the start of an orphan drug program, for approved OMP’s and even for FOMP development. The current legislation is thus not sufficient to give all the patients suffering from orphan diseases access to treatments with the same quality as other patients. As a result, to address the found skewed distribution, additional (financial) incentives have to be implemented to encourage drug development for rare diseases having a prevalence below 1/100,000. In addition, the involved large-sized firms in FOMP development often have obtained the necessary experience to bring the FOMP to the market, however, also the FOMP’s owned by SME’s should be able to obtain market authorization. To address the skewed distribution it is thus also important to focus on SME’s. The EMA addresses this issue by giving sponsors scientific advice and protocol assistance and by having launched a SME office dedicated to the (regulatory) needs of the SME’s. Based on the results of this thesis, new policy measures regarding stimulating pharma innovation by means of regulation have to take into account the following two issues, i.e. equally addressing the unmet medical needs and focusing on inexperienced companies (mostly SME’s) to give them also the possibility to fully benefit from the provided incentives of the regulation. | |
