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Editor-in-Chief: Natalia Ortúzar
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Online ISSN: 1860-7187
April 24, 2012
A New Lease on Life
There is a significant amount of untapped potential in drug development projects that have been shelved for various reasons. Most programs like this are sidelined because of safety issues that cropped up along the way, or a lack of efficacy toward the targeted indication.
One well-known example is that of thalidomide (shown), a drug that was avoided for many years after it was discovered in the early 1960s to be the cause of severe birth defects. Although thalidomide is clearly not the right drug for expectant mothers to take in order to reduce nausea, it has reemerged lately as an anticancer drug: in 2006 the US Food and Drug Administration (FDA) approved Thalamid, a combination of thalidomide and dexamethasone marketed by Celgene, for the treatment for multiple myeloma. Celgene's anticancer drug Revlimid (lenalidomide) is a derivative of thalidomide.
Azidothymidine (AZT) is another high-profile compound with an analogous story: it had been initially explored in the mid-1960s as a possible anticancer compound, but was shelved and largely forgotten for more than two decades until it was found to be an effective treatment for HIV infections (see the Editorial from our November 2010 special issue on HIV research).
From the standpoint of repurposing for off-target indications, failed drugs have the advantage of previously acquired records regarding their safety and efficacy. Reassessing shelved compounds for off-target uses therefore takes advantage of earlier investments of time and funding. Dr. Francis Collins, the Director of the National Institutes of Health (NIH), recently urged pharmaceutical companies to “get those programs out of the deep freeze” and work with the NIH to breathe new life into these programs and to get them onto a different and more promising track.
The complication in this effort is that of intellectual property (IP) rights; some of these cancelled projects may no longer be under IP protection, and so there would be little or no incentive for a given pharmaceutical company to pick up the ball. Although the details have yet to be released, Collins' program proposes finding a way for companies to gain new IP protection, or to otherwise be granted market exclusivity for development projects with expired patents. Pharmaceutical companies will be attracted to projects in which a significant amount of safety and efficacy testing has already been invested; getting the IP hurdle out of the way is the key challenge.