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Zanello et al. Rare Dis Orphan Drugs J 2023;2:9 https://dx.doi.org/10.20517/rdodj.2023.04 Page 9 of 15

allows the possibility of filing a patent in a second medical use, which can lead to the building of a patent
portfolio of higher commercial value for investors. Indeed, interviewees have reported that once the patent
of a second medical use is granted, the protection can be further extended via other types of patents: new
formulations (i.e., pediatric formulation, medical device, and prodrug), dosage, administration route, and
combination of drugs.

Additionally, the non-patentability of the discovery will likely discourage investors. IP protection is thus
considered as a factor of success; the objective is to exploit it, and make good use of the advantages it
provides, e.g., support the return on the investment.

Finally, IP strategy is a complex field, generating a high level of competition. Patents have to be carefully
designed as they are often attacked and dismissed by competitors. For non-specialists, and especially in the
case of a repurposing approach conducted by academics, the importance of Tech Transfer Offices is crucial
to help navigate the field, avoid pitfalls (e.g., no publication when a patent is sought) and build a strong IP
strategy.

Development/Business planning requires defining upfront the end of the journey and each step of
the development path
The granting of an orphan designation does not seem to be necessarily a key element in a repurposing
approach, whereas the regulatory approval, i.e., granting of a Marketing Authorization, is more often seen
as a goal.

Regulatory issues have been reported, such as the need for placebo data which was not anticipated or the
importance of choosing endpoints that are relevant for the patients. In those cases, the regulatory system
offers tools to overcome such barriers, such as the FDA meeting or EMA Scientific Advice for example.
EMA has also opened a pilot on repurposing to support not-for-profit organizations and academia . FDA
[9]
[22]
allows 505(b)(2) application for a not previously approved indication for a marketed product .
Market access is seen as a big risk for various reasons. While the availability of the product for patients and
the granting of reimbursement are seen as success factors, difficulties are reported in relation to several
aspects: (a) the estimate of the target population for which accurate prevalence figures are needed; (b) the
anticipation of the generics & compounded products competition and the underestimation of the off-label
use which leads to incorrect predictions; and (c) the commercialization costs that might be higher than
expected in some countries and might represent an issue if not adequately anticipated.

All this has consequences on the selection and implementation of the economic model, which is seen as one
of the main challenges in the repurposing approaches. As a mitigation measure, some interviewees
mentioned the need to refine and adapt their business plan during the development path in order to better
reflect the R&D costs and the commercialization costs and hence to adjust the price.

The principles expressed in the IRDiRC Orphan Drug Development Guidebook (ODDG) published in
[23]
2020 are applicable here, i.e., early planning of the development path, best use of all the tools available,
early and continued dialogue with regulators and with Health Technology Assessment (HTA)/payers to
anticipate the access phase since the beginning. However, the ODDG had not considered the aspects related
specifically to repurposing and we aim to add a specific module to the existing materials. This represents a
key IRDiRC activity in 2023 .
[24]