Regulatory Focus™ > News Articles > To Meet Ebola Threat, Father of FDA's Priority Review Voucher System Calls for Reforms

To Meet Ebola Threat, Father of FDA's Priority Review Voucher System Calls for Reforms

Posted 13 October 2014 | By Alexander Gaffney, RAC

To Meet Ebola Threat, Father of FDA's Priority Review Voucher System Calls for Reforms

One of the fathers of a little-known and lesser-used regulatory pathway meant to incentivize the approval of new drugs for so-called "neglected tropical diseases" says Congress needs to include Ebola on the short list of diseases eligible for incentives.

Background

So called "tropical" diseases are defined by statute as infectious diseases which do not affect developed nations and disproportionately affect poor and marginalized nations. Such diseases are typically not subject to the same levels of investment and research as are other diseases, in part because the markets for those products are generally less affluent, leaving companies less able to obtain a positive return on their investment (particularly if research and development was conducted in regions with higher costs).

"Because these diseases are found primarily in poor and developing countries, existing incentives have been insufficient to encourage development of new and innovative drug therapies," explained the US Food and Drug Administration (FDA) in a 2008 guidance document on the subject. FDA said it was taking an interest in the topic given the needs of other countries and the ability of those diseases to affect Americans in an increasingly globalized economy.

In order to incentivize development of treatments for tropical diseases, in 2007 Congress passed into law the Food and Drug Administration Amendments Act (FDAAA), Section 1102 of which established the tropical disease priority review voucher system—a novel system of incentives first proposed in a 2006 Health Affairs paper.

Under the system, companies that receive FDA approval for a tropical disease treatment are eligible to receive a transferrable voucher that allows the bearer to receive six-month priority review status for any future product. Products undergoing priority review are generally given an approval decision—positive or negative—within six months after the applicant's filing date instead of the standard 10-month review period for most other drugs.

Under normal circumstances, FDA only grants priority review status to products which fill a treatment void or would otherwise represent a significant advancement compared to existing treatments. Because these reviews cost more than traditional drug reviews, the cost per application is more. However, under the voucher program, any company willing to pay the additional cost of the review may have its product reviewed by FDA, the agency explained.

Short List of Eligible Diseases

Under FDA's 2008 guidance on tropical disease priority review vouchers, just 16 diseases are eligible for the voucher:

Eligible Diseases Under the Tropical Disease Priority Review Voucher System
MalariaBlinding trachoma
Buruli UlcerCholera
Dengue/Dengue haemorrhagic feverDracunculiasis (guinea-worm disease)
FascioliasisHuman African trypanosomiasis
LeishmaniasisLeprosy
Lymphatic filariasisOnchocerciasis
SchistosomiasisSoil transmitted helminthiasis
YawsTuberculosis

Notably not on that list of diseases: Ebola, which prior to 2014 had only sporadic outbreaks which were quickly contained and killed relatively few people compared to diseases like malaria and cholera.

But FDAAA also contains a provision by which FDA can make additions to its list of designated diseases eligible under the priority voucher system. FDA is permitted to designate "Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations" as eligible.

Father of Voucher System: Add Ebola, Others

And in a new opinion piece in the San Francisco Chronicle, David Ridley, one of the authors of the original 2006 Health Affairs piece which first proposed the voucher system, argues Congress should add Ebola to the voucher list in order to incentivize development of drugs to treat the deadly disease.

"To improve on the current voucher program, Congress should add other infectious diseases for which the burden of disease is great and the profit potential is small," Ridley writes. "Ebola, which has already killed more than 3,000 people in 2014, is one obvious example, but so is chagas, which killed an estimated 8,000 people in 2012, mostly in Central and South America," Ridley added.

However, in this area Congress has already authorized FDA to do more. The agency could, at the urging of FDA Commissioner Margaret Hamburg or Health and Human Services Secretary Sylvia Burwell, add Ebola (and other diseases) to its list of eligible voucher recipients in relatively short order. And since Congress is currently on recess in order to campaign for re-election, FDA might be able to move considerably more quickly than Congress.

However, any incentives in this area might do little to stop the current Ebola outbreak or spur new treatments. As the development of most new therapies takes years, if not decades, FDA's action might only encourage long-term solutions, not short-term ones. For that, the agency is more likely to turn to its existing and emergency authorities, which permit it to authorize the use of investigational treatments. (For more, see Regulatory Focus' Ebola Explainer)

Voucher Problems Identified

Even if FDA does act on Ridley's recommendations and acts within its current authority, Ridley takes stock of a host of other problems which have hamstrung the program's effect and can only be solved by congressional action.

For example, Ridley notes that some problems have limited the usefulness of the tropical priority disease voucher—problems which have not faced a similar voucher system created in 2012 under the Food and Drug Administration Safety and Innovation Act (FDASIA).

Despite high expectations for the program, the tropical disease voucher system hasn't been used much, in part because it's somewhat restrictive. As FDA explains in its guidance document on the voucher, "The sponsor redeeming the voucher must notify FDA of their intent to submit a human drug application with a priority review voucher at least 365 days prior to submission of the human drug application for which a priority review voucher will be used to obtain a priority review." That advance review time makes it impractical for many companies, which may not be willing to purchase a voucher until they know their product will be able to be submitted to FDA.

That limitation stands in contrast to FDA's rare pediatric disease voucher system, which also gives priority review vouchers, but allows companies to use the vouchers with just 90 days advance notice given to FDA—a major benefit to companies which might not know if a drug candidate is likely to succeed until near the end of a clinical development program. The small change is apparently worth big money. In 2014, pharmaceutical companies Sanofi and Regeneron jointly purchased a priority review voucher for $67.5 million from BioMarin, which had obtained the voucher after FDA approved its rare disease drug Vimizim.

Contrast that sale to the fate of tropical disease vouchers. Despite recent attempts by Knight Therapeutics, no company has yet been able to sell a tropical disease voucher. The only time the voucher has been used (by the company which obtained it), FDA rejected the application.

Ridley said the tropical disease voucher redemption time should be reduced from one year to three months in order to "increase the value of the voucher by making it more useful for the bearer."

Other Reforms Offered

Ridley calls for other reforms as well, including allowing users of the vouchers to be allowed to resell them multiple times, which would decrease the risk of purchasing the voucher. At present, if a company with a product buys a voucher only to have their product fail in late-stage testing, they are unable to resell the voucher.

Ridley also calls on companies to report on the affordability of the drug in the countries in which it is sold, and for Congress to "restrict eligibility for the voucher to novel products that have not been approved in other countries more than two years prior to FDA submission."

Ridley says he hoped that Congress' larger "21st Century Cures Initiative" will adopt at least some, if not all of his proposals. The House Energy and Commerce Committee has said it plans to take up legislation aimed at regulatory reforms in the healthcare sector in early 2015.

 

Ridley Op-Ed


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