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Orphan Drug Model Should Include PGx Therapeutics, McClellan Says

WASHINGTON, DC – The existing regulatory model for orphan drug development should encourage sponsors to develop more personalized treatments in broader disease settings, former FDA Commissioner Mark McClellan said this week.
“What one might hope for … is that the approach that’s used for orphan drugs … could become much more of the norm for developing drugs for broader types of diseases,” McClellan said at a conference here hosted by the Personalized Medicine Coalition.
McClellan, now a senior fellow at the Brookings Institution and former administrator of the Centers for Medicare & Medicaid Services, spoke at the PMC’s “21st Century Medicine: Personalized and Evidence-Based” conference.
Under the Orphan Drug Act of 1983, the FDA can award drug makers seven years of marketing exclusivity, provide tax breaks to supplant research costs, waive user fees, expedite reviews, and give grants for new research into rare diseases. Health care policy circles routinely call the program successful, having approved more than 200 drugs for rare diseases since it was started.
Industry participants have long suggested the need for a similarly incentivized “orphan” setting to spur the development of pharmacogenomics-based drugs and technologies targeted for specific populations in rare disease markets.
For instance, the C-Path Institute last year announced that it was starting a collaboration with physicians, patient groups, and researchers to create a Rare/Orphan Disease Registry order to support new diagnostic and therapeutic clinical trials for disorders that offer little financial incentive for drug makers to pursue on their own [see PGx Reporter 08-02-2007].
This week, McClellan suggested that the regulatory model for orphan drugs can initially be used to approve drugs for a subset of populations in what he called a “targeted approval.” FDA officials can then use outcomes databases and post-marketing studies to monitor how the drug performs in the post-market setting and decide whether to extend the life-cycle of the drug to broader populations and to other disease settings.
“There will be a lot more learning in the post-market setting” allowing us to “branch out from the initial targeted approvals to a much better understanding of how patients can more generally respond to drugs,” McClellan said. This can be “done in a way where the public has a lot of confidence that drugs aren’t being used widely on the market for conditions where they are either ineffective, or they are causing harm.”

“What one might hope for … is that the approach that’s used for orphan drugs … could become much more of the norm for developing drugs for broader types of diseases.”

Such confidence has not always been universal. In a draft report it released last winter, the HHS advised pharma companies against using PGx tools in the orphan-drug setting if they are considering using the technology to broaden the drug’s indications beyond rare diseases. Instead, drug-diagnostic co-development may be the best way for drug makers to fuel adoption of PGx tools, the report suggested [see PGx Reporter 03-28-2007]. 
However, many drug companies are doing exactly this in embracing the “nichebuster” model. In this approach, instead of investing large sums of money in one “blockbuster” drug for a broad population, the focus is on identifying biomarkers that target subpopulations in multiple disease markets [see PGx Reporter 03-28-2007]. Bristol-Myers Squibb, Novartis, and Pfizer have all unveiled recent plans to restructure their R&D setup to incorporate PGx tools and identify safety and efficacy biomarkers to develop targeted therapies.
According to the HHS report, however, pharma’s growing embrace of biomarker-backed research into multiple smaller disease populations doesn’t automatically confer orphan status for PGx drugs. In fact, misuse of the orphan drug program may lead to a pushback from the FDA, the report warned.
This week, McClellan emphasized that drug makers can use the orphan drug model appropriately to further the development of personalized medicine when used in concert with heightened post-marketing surveillance.
The FDA Amendments Act of 2007 (H.R.2900) outlines a section that empowers the HHS Secretary to require companies to conduct post-marketing studies of an FDA-approved drug, a power that the agency currently does not have.
“If you show that a drug is safe and effective for a narrow population, there will be ongoing questions about what happens when physicians and patients start using it in other contexts,” he said. In those cases “developing active surveillance systems can help.”

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