Bipartisan members of the US Senate's healthcare oversight committee plan to introduce legislation that would amend a little-used regulatory program in the hopes of spurring the development of treatments for the Ebola virus.
The program, known as the neglected tropical disease priority review voucher program, was created in 2007 under the Food and Drug Administration Amendments Act (FDAAA). The voucher program, first envisioned in a 2006 Health Affairs policy paper, is intended to speed up and incentivize the development of treatments for so-called "neglected" tropical diseases.
"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).
The voucher program aims to incentivize development in these areas by providing companies who successfully develop drugs for certain tropical diseases with a transferrable voucher which entitles its recipient to a six-month, priority review process at FDA for any drug product. The normal regulatory review process takes 10 months, assuming there are no delays or setbacks, which are not uncommon.
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|
|Dengue/Dengue haemorrhagic fever||Dracunculiasis (guinea-worm disease)|
|Fascioliasis||Human African trypanosomiasis|
|Schistosomiasis||Soil transmitted helminthiasis|
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.
Advocate Presses for More
As Regulatory Focus first reported this month , one of the intellectual fathers of the priority review voucher program, David Ridley, recently proposed expanding the voucher program to include Ebola and several other neglected diseases. The status would serve to incentivize development of drugs to treat the deadly disease, he argued.
"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.
Influential Senators: Add Ebola
Now the two most influential members of the US Senate's healthcare oversight committee, the Health, Education, Labor and Pensions (HELP) Committee are agreeing to do just that.
In a statement, Sens. Tom Harkin (D-IA), the Chairman of the committee, and Lamar Alexander (R-TN), its Ranking Republican member, said they plan to soon introduce legislation that would "speed the development of treatments and vaccines for Ebola by adding Ebola to FDA's priority review 'voucher' program."
"When enacted, as I hope it will be, this legislation will strengthen our response to Ebola and help innovators to continue their work to develop Ebola treatments and vaccines. I urge my colleagues to join me in passing this bill and continuing to invest in the public health agencies on the frontlines of the U.S. response to Ebola," Harkin explained. Alexander noted that the world is in "desperate need of a vaccine" to treat the disease.
Wait: FDA Already Can Do This
There's just one catch: FDA already has the authority to add Ebola to the list.
Under Section 1102 of FDAAA, "tropical disease"—in addition to 16 explicitly contained in the statute—can include "Any other infectious disease for which there is no significant market in developed nations and that disproportionately affects poor and marginalized populations, designated by regulation by the Secretary." (Emphasis added)
That authority would presumably allow the Secretary of Health and Human Services (DHHS) Sylvia Matthew Burwell or FDA Commissioner Margaret Hamburg to immediately declare the Ebola virus eligible for incentives under the priority review voucher program.
However, given the usual delays inherent in the rulemaking (i.e. regulation) process, it's unclear if FDA would be able to pass changes through regulation more quickly than Congress could make them through statute.
The bill, while well-intentioned, may not work quite as well as legislators hope, and might require changes to be made to the program beyond just adding Ebola to the list of eligible diseases.
Because subsidies under the act are only given to companies which obtain full approval—not Emergency Use Authorization (EUA) or an emergency investigational new drug application (IND)—it could be months, if not much longer, before a product is eligible for the incentive. Legislators might consider adding in "active emergency" provisions to help combat an ongoing crisis, for example.
Further, the voucher has not been particularly successful . Despite FDA issuing several of the vouchers, none have ever been used successfully by a company. And despite the recent sale of a priority review voucher for $67.5 million, that voucher was for an entirely separate and statutorily distinct program known as the rare pediatric disease voucher program. Critics have called that program superior because it allows recipients of the voucher to use it with just 90 days advance notice to FDA. The tropical disease voucher, by contrast, can only be redeemed by a company giving FDA a full 365 days advance notice—and cannot be sold more than once. Legislators might consider bringing the voucher in line with the pediatric rare disease voucher, for example.
Third, use of the vouchers is not without cost. FDA currently charges companies $2,562,000 to use a tropical disease priority review voucher . For some companies, and particularly those with a potential blockbuster seeking a shortcut to market, the fee is akin to a rounding error on potential profits. But for many other drugs, the significant cost, paired with the lack of guarantees that the application will even be successful, may be seen as an added cost and thus decrease its value to potential purchasers. The cost of the voucher is intended to offset additional costs incurred by FDA during the accelerated review.
Finally, it's not clear the voucher will have much of an impact. There are already nearly a dozen investigational Ebola products trying to reach the market, and some have already been used to help treat patients. Given the interest in developing product for Ebola during the current outbreak, it's not clear if additional incentives would be of much help for the current Ebola outbreak. It might, however, help develop additional treatments for future outbreaks.
Additional Reading on the Priority Review Voucher Program
Focus' Regulatory Explainer on Ebola