Conventional drug repositioning: the general advantages
1. Significant reduction in the risk of failure
Based on existing approved drugs, repositioning reduces the risk of failure due to a combination of the following features:
- Safety: The general case is that the development risk for a new indication is reduced for a known drug that has been shown to be sufficiently safe, even if it has fallen short of targeted end-points in its original indication. The drug then competes with standard care in terms of efficacy, not safety, eliminating the approximately 30% of drug failures in clinical trials due to safety considerations. The availability of bibliographical studies on toxicity will guide the need for supplementary clinical toxicity testing and reduce the number of patients included in new clinical trials to a minimum. As will be specified below, Reponex has access to actual preclinical and clinical phase I data through an agreement with a strategic partner.
- Efficacy: A newly developed drug has a significant risk of not reaching its efficacy end-points in its original indication and may be shelved or even withdrawn after launch if initial efficacy data are not confirmed. This is a further major risk in de novo drug development, which is bypassed or considerably reduced by judicious repositioning to indications for which the drug is much more likely to be effective. Together, the effects of a) and b) are estimated to increase the chance of success in clinical trials by 250% in relation to a new drug .
- Leverage from existing scientific publications: This benefits the optimal design and execution of clinical trials.
- Significantly reduced failure rate of approval: This results from the combination of the effects of the above features.
2. Intellectual property (IP) rights
Repositioning gives the possibilities of obtaining strong patents, even if the original patents on the active pharmaceutical ingredient are still in force. The subject matter that can lead to novelty and inventive step, and hence to patentable claims, include the following:
- New indications: These may be backed up by proof-of-concept examples.
- New dosage regimens: These are appropriate for the new indications and may be quite dissimilar to previous dosage schemes for the original indications.
- New administration methods: These are adapted to the new indications and chosen to have special advantages for their treatment, i.e. local application to the site of the pathology.
- Different formulations: These follow directly from any new administration method and are designed to maximize efficacy and acceptability.
Reponex’s intellectual property portfolio will be described under the individual clinical development projects.
3. Cost cutting
It has been reported that the cost of relaunching a repositioned drug averages $8.4 million, whereas relaunching a new formulation of an existing drug in its original indication costs an average $41.3 million and launching a new drug averages more than $1.3 billion. Thus the cost of bringing a repositioned drug to market may be less than 1% of launching a new drug.
4. Reduced time to market
The advantages listed under 1. above are also reflected in an accelerated development and approval timeline. A de novo standard drug development typically takes well over 10 years to market launch, whereas the time for a repositioned drug is 3-12 years. At market launch the repositioned drug is in an equal position to the newly developed standard drug.
5. Market/financial potential
There are a number of recorded cases of repositioned drugs achieving blockbuster status, even if there is no change in route of administration to improve their safety profile. A notable example has been thalidomide and its analogues, notoriously dangerous because of teratogenic effects in pregnancy, but now achieving billion-dollar revenues for the treatment of cancers including multiple myelomatosis. Viagra is a drug that was not meeting its primary efficacy target as a vasodilatory treatment for high blood pressure, but proved to be highly effective for treating erectile dysfunction and continues to provide an annual revenue of over $2 billion.