Bruce Bloom, JD, DDS

The case for supporting off-label use or commercialization in drugs for “unsolved” diseases.

	 	There are over 7,000 “unsolved” diseases for which patients have no universally successful treatment. There are also thousands of generic drugs that can be repurposed to help these patients. Built on knowledge from scientific discoveries, anecdotal evidence, and/or bioinformatics, generic drug repurposing research can often lead to quick and affordable development of “new” medical solutions. Once a generic drug repurposing opportunity has been identified, a key issue is whether the clinical trial validation should focus on supporting a path to commercialization or to physician off-label use. The direction of focus depends on the entity supporting the clinical trial development.	 	Development entities that support generic drug repurposing clinical trials are either commercial or philanthropic. When thinking about outcomes, commercial entities (pharma, biotech, financial investors) typically focus on financial and shareholder value, while philanthropic entities (patient advocacy groups, foundations, individual philanthropists, government) primarily focus on patient impact. 	 	Before a commercial entity will move forward with a generic drug repurposing clinical trial, there are three key issues it needs to evaluate. First, there needs to be a possibility for significant financial profit. Several factors contribute to profit potential, including patent protection (arising from modifications to the generic drug), market exclusivity, and/or manufacturing exclusivity. If patent/exclusivity is possible, then the commercial entity next gathers additional information to determine the potential return on investment (ROI) of the clinical trial. Finally, the commercial entity will determine if the specific opportunity fits into its portfolio and aligns with its business goals. If any of the decision points above is negative, then the project normally stops. A commercial entity is unlikely to fund or seek funding for a clinical trial simply to provide the support for physician off-label use.	 	The decision process is different for philanthropic entities. Philanthropic entities might start with the same commercial evaluation to determine if a clinical trial and regulatory approval path could yield strong profits and financial ROI. If so, they might be able to find a commercial partner who could bring the repurposed generic drug to market. But what if there is weak ROI due to small geographic exclusivity, short time exclusivity, tiny market size (ultra-rare disease), lack of patent protection, high regulatory cost, long regulatory process, high manufacturing costs, or strong market competition? 	 	Philanthropic entities might be able to entice concessionary impact investors

 to fund these clinical trials and other regulatory costs, with the hope of recouping some or all of their investment. Although there are not many current examples of this strategy, there are a few organizations beginning to look at impact investment for break-even commercial generic drug repurposing.	 	A more likely scenario in cases of repurposing opportunities with weak or no potential financial return, is that the philanthropic entity would opt to simply secure funding for a proof of concept clinical trial robust enough to support off-label use of the repurposed drug. Off-label clinical trials can be successful in changing clinical practice when the disease situation is dire, the repurposed drug is relatively safe, widely available and affordable, and the patient impact is likely to be significantly positive. Clinical trials that fit these parameters may provide the data necessary to support physicians and their patients to adopt the repurposed therapy off-label, meeting the goal of philanthropic entities. Off-label focused clinical trials have already been successful, especially in rare diseases

.	 	Regardless of whether a clinical trial is funded by a commercial or philanthropic entity, generic drug repurposing provides an alternative drug development path to quickly and inexpensively create medical solutions to unmet patient needs. Repurposing is an important healthcare strategy, even when there is no commercialization potential. This is especially true for rare or neglected disease populations, where commercialization is more challenging.	 	Bruce Bloom, JD, DDS is President and Chief Science Officer for 

. He directs the operation of the public charity dedicated to improving the patient quality and length of life by facilitation pilot clinical trials that drive more repurposed treatments to more patients more quickly. Dr. Bloom holds a Juris Doctor degree from the IIT Chicago-Kent College of Law, a Doctor of Dental Surgery degree from the University of Illinois Medical Center, and a Bachelor of Science degree in Biology from University of Illinois.	 	 	

			https://thegiin.org/impact-investing/need-to-know/#s2		

			http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819393/		

			http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705607/

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Generic drug repurposing can often create medical solutions regardless of the supporting entity. “Unsolved” diseases can benefit from this strategy despite commercialization challenges.

Bruce Bloom, JD, DDS

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Generic Drug Repurposing Clinical Trials