As the Senate debates whether to extend or make permanent the US Food and Drug Administration's (FDA) priority review voucher (PRV) program, a Harvard medicine professor says that so far, at least for tropical diseases, there's "little reliable evidence" that the program has spurred novel drug development.
Since 2007, the FDA has issued seven PRVs (the most recent of which came earlier this month), which allow sponsors to speed the review of any one of its new drug products from the standard 10-month review to a six-month expedited review.
The PRVs are awarded to companies sponsoring approved drugs to treat qualifying neglected tropical diseases, such as tuberculosis, malaria, schistosomiasis and yaws, as well as rare pediatric diseases. The vouchers can also be sold or exchanged, which in one case brought in $350 million for United Therapeutics.
But whether the program has actually led companies to develop new drugs to treat neglected tropical diseases remains to be seen.
Aaron Kesselheim, Professor of Medicine at Harvard, initially in 2008 raised questions about the utility of such a program. And now that the PRVs for tropical diseases have been available for seven years, he's raising new questions about whether the voucher system actually works, or whether it needs to be redesigned.
On the tropical disease front, Kesselheim says there's scant evidence that the program’s primary intention of spurring novel drug development has been met.
The first tropical disease voucher was granted in 2009 to Novartis for the antimalarial artemether-lumefantrine, though at the time of FDA approval, the drug was approved in more than 80 countries.
Last year, Knight Therapeutics also received a voucher for miltefosine, a treatment for leishmaniasis, though the drug was registered outside the US a decade before its FDA review, and Knight was not involved in its development.
Kesselheim also notes that the development of other drugs awarded PRVs -- artemether-lumefantrine, dinuximab and cholic acid-- were based on significant public sector investment.
"One way to potentially prevent such windfalls would be to redesign the voucher system so that drug companies would have to show some level of investment in a new drug’s development before earning the reward," he says.
Kesselheim also questions whether the prospect of earning $350 million "a decade or so in the future" for a voucher is enough to encourage a large pharmaceutical manufacturer to invest in and take upward of a decade to develop a novel treatment for a tropical or rare pediatric disease.
"Nonprofit drug manufacturers may be in a better position to take this value into account," he adds.
In addition to the question marks around innovation, Kesselheim also says the program "clearly does not ensure affordable access to the products either in the US (elosulfase costs $380 000 per year) or overseas."
He calls to amend the program to ensure that the use or sale of a voucher is "conditional upon demonstrating equitable marketing of the drug" in low-income or resource-poor countries where many of these drugs would be helpful.
"Several more promising approaches exist to promote discovery of new treatments for neglected tropical diseases or other overlooked disease classes. In particular, greater funding of basic science research would help identify novel targets for therapy," he continues.
He also calls on Congress to further reexamine whether the program "has actually met its goals" or if it can be tailored "to better reward true innovation and ensure affordable access to life-saving therapies."