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

treatments, especially in the field of rare diseases, where 95% of the 7,000 to 8,000 rare diseases have no
approved treatment. A few well-known success stories are good illustrations of successful academia-
industry DR collaborations, which may be viewed as the tip of the iceberg. There are also bitter and
anonymous failures of collaboration.

The purpose of this perspective paper is to explore academia-industry collaborations in DR of medicinal
products for rare diseases through their main challenges and successes and through select DR case studies.
Key questions are raised to understand why, when, and how to implement a relevant collaboration. Some
recommendations are also proposed.

DEFINITION OF DRUG REPURPOSING
DR is also known as drug repositioning, reprofiling, retasking, rediscovery, rescue, etc. While reflecting on
different types of situations encountered and described in the literature , all these terms are synonyms and
[1]
refer to a similar process that identifies new indications for approved, investigational, failed or shelved
drugs/compounds. At present, the terms are all used interchangeably. This article will refer to all
terminologies as “drug repurposing” for consistency purposes. As of November 1, 2022, a search on
PubMed listed 1973 results mentioning “drug repurposing” and 861 results mentioning “drug
repositioning” for 2022.

DRUG REPURPOSING PROVIDES AN OPPORTUNITY FOR RARE DISEASES
Much has been said about DR over the last two years with the COVID-19 pandemic. An editorial entitled
“COVID-19 and the DR Tsunami”, published in July 2020, reflects an unprecedented wave to repurpose
existing drugs . The aim is to vastly accelerate the usually long approval process of drugs , which is a
[3]
[2]
common goal and an objective also shared with rare disease patients desperately waiting for treatments.
Today there are an estimated 350 million people worldwide living with a rare disease. 7,000 to 8,000 rare
diseases have been identified, with 250-280 new diseases discovered annually. Only about 5% of rare
diseases are estimated to have approved treatments.

In Europe, between 2000 and 2021, 245 orphan drugs, so named for the rare diseases they treat, have been
[4]
[5]
approved. They cover a total of 148 rare diseases . About 20% of orphan drugs are repurposed drugs .
[6]
There is an urgent need for treatments as most of the rare diseases are life-threatening. DR may be a
particularly attractive option for the development of treatments for rare diseases. Of note, oncology and
infection are together the most common disease areas for DR so far .
[7]

SELECT EXAMPLES OF SUCCESSFUL DRUG REPURPOSING
The most famous case of DR is probably the development of sildenafil which is also a good example of both
[8]
investigational and approved DR . Sildenafil, a phosphodiesterase-5 (PDE5) inhibitor initially explored as a
treatment for angina pectoris and hypertension by Pfizer, was tested unsuccessfully in these diseases and
eventually demonstrated efficacy in treating erectile dysfunction (with the trade name Viagra®) and then
pulmonary arterial hypertension (with the trade name Revatio®) .
[9]

The clinical trials in angina, which had started in 1989, were disappointing, and sildenafil failed in the Phase
II trial. However, a side effect (induction of penile erection) was serendipitously found during the Phase I
and II clinical trials and redirected sildenafil to the treatment of erectile dysfunctions (ED). This indication