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Fetro. Rare Dis Orphan Drugs J 2023;2:7 https://dx.doi.org/10.20517/rdodj.2023.06 Page 7 of 16

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time-consuming, and risky process . Furthermore, it does not always succeed. Like de novo drug
development, DR may also fail in late-stage development. That was the case for latrepirdine, originally
developed and marketed as an H1-antihistamine for the treatment of skin allergy and allergic rhinitis.
Latrepirdine was repurposed as a treatment for Huntington’s disease (HD). Following encouraging phase II
trials and preliminary reports showing its neuroprotective functions and ability to enhance cognition in
[24]
animal models, it failed to show efficacy in phase III trials in HD patients .
Some authors have underlined the importance of confirmatory validation studies for a successful translation
of academic results to the industry before larger investments are made .
[25]
Such gaps between academia and industry should favor rather than discourage a move towards stronger
collaboration. Both have their respective roles to play in a drug development process; there is
complementarity and not duplication, and there may be mutual support learning from one another.
Moreover, while repurposing previously relied on some serendipity, it has more recently evolved to
continuous advances made in the field of data sciences and to approaches integrating -among others-
computational assistance using Big Data and Artificial Intelligence .
[26]
WHEN
There is no ideal timing to start a collaboration
There are rather special circumstances leading to potential opportunities or not. For instance, one of the
nightmares of a pharmaceutical company is to get safety issues during pivotal studies close to the approval
stage. That was the case for alpelisib when Canaud’s team asked for the molecule to be tested in PROS.
Although based on an exhaustive literature review and spectacular first results in mice and patients, the
alpelisib request was badly timed. The phase III trial of alpelisib in breast cancer was still ongoing. The
detection of a potentially serious adverse event during a clinical trial in PROS could have jeopardized the
drug development for both indications.

Academia-industry collaboration may start as early as possible within a co-development framework or
should be at least anticipated to avoid unexpected issues such as the unpleasant surprise for the industry to
learn one of its drugs is unexpectedly repurposed by an academic team in an out-of-scope indication, or the
huge frustration for the academic team who will not be able to develop a promising candidate owned by
industry and not part of its strategy. It must be noted here that large pharmaceutical companies do not have
the same expectations as smaller ones. They prefer late-stage development projects (Phase II and onwards)
in which they have experience and which are also a way to mitigate the risks.

Line extension or label expansion is not the right time for a collaboration
DR may be part of an anticipated strategy from the industry in the early drug development process. Rather
than DR, it is considered as line extension or label expansion that is conceived from the outset of the
program. It is part of life cycle management (LCM) activities whose objective is to maximize the value of the
products with new indications, improved formulation, new packaging, etc., and to allow for patent
[27]
extension . Only the marketing authorization holder of a drug can currently apply for an extension of its
marketing authorization. When drugs are repurposed on the basis of on-target effects (as is the case with
sildenafil and alpelisib), it means that work may be undertaken by the pharmaceutical company owning the
molecule. Company data are not available to academic investigators.

Intellectual property considerations are a critical element when starting a collaboration
Drugs are protected by patents and supplementary protection certificates and may benefit from another