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Recycling, the Pharma Way…

In this day and time, we are familiar with the importance of recycling items that would ordinarily be discarded as trash. We all know why it is a good idea and we have clearly labeled containers in grocery stores, restaurants, offices, and our homes constantly reminding us to do the right thing. However, you may not think that this concept has parallels in the drug industry, yet it does. Each year pharmaceutical companies and biotechnology firms spend multiple millions of dollars on research and development of products. Sometimes, the drugs developed are successful for their intended use, and sometimes, they aren’t. Have you ever thought about what happens to those drugs that aren’t successful? Or the other uses of those that are successful?

As a young statistician in the industry, many years ago, I had the opportunity to witness the recycling of a failed product, Adefovir Dipivoxil. As you may know, adefovir was developed and tested by Gilead Sciences for the treatment of HIV.  Numerous clinical trials were conducted for this indication. As the results were analyzed, a safety signal linked the compound to renal toxicities when dosed at 60 or 120 mg. Based on this signal, the advisory committee recommended the U.S. Food and Drug Administration (FDA) not to approve the drug. The FDA took the advisory committee’s recommendation and rejected Gilead Science’s application for approval.

It is at this point that Gilead could have put adefovir on the proverbial shelf and chosen to overlook the impressive antiviral effect of the compound, but they did not. Instead, they repackaged adefovir for use at a lower, safer dose for use in treatment of Hepatitis B. That recycled product was approved by FDA in 2002. At that advisory committee meeting, Gilead was commended for its ‘recycling’ efforts.  I have never forgotten that moment in the meeting, and find myself always looking for other examples of recycled or repackaged products.

You may have heard that the U.S. Federal Drug Administration (FDA) recently approved Gilead’s Truvada as the first HIV preventative drug. In this case, some of the early testing was already complete as Truvada was previously approved for use as a treatment for HIV-infected individuals before clinical trials focused on pre-exposure prophylaxis (PrEP) began. For this indication, two clinical trials were conducted by the University of California San Francisco and the University of Washington. The Preexposure Prophylaxis Initiative study (iPrEx) study followed approximately 2,500 men and transgender women who engaged in high-risk behavior, and the Partners PrEP study followed approximately 4,700 heterosexual couples with one infected and one uninfected partner.  For both studies, the efficacy results were published prior to the submission of data to regulatory authorities. Using additional data that were collected during these two trials, Gilead generated supplemental analyses such as adverse events, demographics, and adherence to dosing instructions that were required for regulatory submission.

Through careful data analysis, it was shown that Truvada reduced the risk of HIV infection by 42% in the iPrEx trial and reduced the risk of infection by 75% in the PrEP trial. Based on these results, the FDA approved Truvada to reduce the risk of HIV infection in uninfected, but high-risk individuals. Now that Truvada is approved for use in this indication, further studies will be needed to examine patient behaviors and adherence to dosing instructions. From these studies, additional information may be learned that could lead to other uses for Truvada. That’s recycling, the pharma way!

If you are thinking of taking a ‘green’ approach to drug development, we can help! PharPoint has a highly experienced team of biostatistics, data management, and clinical professionals who have contributed to regulatory submissions like those implemented Adefovir (Hepsera) and Truvada. As a small, client-focused service provider, we have the ability to customize solutions to fit your needs. Contact us today to find out how we can help complete your study the better way.

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