On Wednesday the Senate Health, Education, Labor & Pensions (HELP) Committee advanced seven bills tied to their work on counterpart legislation to the 21st Century Cures Act. One of the seven bills would add the Zika virus to a list of neglected tropical diseases which are eligible to receive a coveted priority review voucher from the Food and Drug Administration (FDA).
Ideally, the voucher would add incentives for companies to develop a treatment or vaccine for Zika, which has exploded throughout Brazil and the Americas. Spread by mosquitos, the disease has been linked to severe neurological diseases in adults and microcephaly in babies born to infected mothers.
No vaccine currently exists for the disease and the race is on to develop and manufacture a treatment to address the growing medical need. Currently, some 67 companies are working on Zika-related products, according to the World Health Organization.
Adding the virus to the tropical disease priority review voucher (PRV) program would provide an additional award for companies successfully applying in the U.S. However, the program has been heavily criticized by some, including the humanitarian organization Doctors Without Borders, for failing to properly award true innovation.
Regulatory and financial incentives
The tropical disease priority review program awards companies who successfully license a drug treating one of the listed tropical diseases with a voucher the company can use to expedite future regulatory reviews. If used to advance the review of another drug, the vouchers cut the FDA's review period by four months, from ten months to six months. While seemingly a short amount of time, the faster turnaround can help a company establish market share or boost revenues from a new drug launch.
Companies can also resell the vouchers, often for hundreds of millions of dollars. Four vouchers awarded through a similar pathway fetched prices ranging from $67.5 million dollars to $350 million dollars.
Gaming the system
Designed to reward innovation and boost R&D in neglected diseases, these vouchers can be gamed by companies seeking to push an older drug across the regulatory finish line.
There is no requirement a company needs to actually invent the drug. Under former CEO Martin Shkreli, the biotech KaloBios attempted to buy the rights to a treatment for Chagas diease in order to obtain a voucher. While the treatment had been available cheaply for years, it hadn't received approval in the U.S. and could therefore still be eligible for a voucher.
In November 2015, Doctors Without Borders (MSF) sent a letter to the Senate HELP Committee asking it to reform the tropical disease PRV program as it drafts major biomedical legislation related to the 21st Century Cures Act (which was previously passed by the House of Representatives).
"The lack of requirements for a product to be novel or to be made available to and affordable for those whom the product is designed to treat or protect are two critical flaws in the design of the program that remain unaddressed," MSF said in the letter.
According to Judit Sanjuan, US Manager of MSF's Access Campaign, Doctors Without Borders supports rewarding innovation but wants the awards to be for completely new drugs, and for drugs which will be affordable for patients.
"We are just saying look at how it works as an incentive for innovation. It has not worked. Three times it has been given, three times it has been gamed. So therefore, before you make it bigger and bigger, make sure it works," Sanjuan said.
The last two times a tropical disease PRV has been awarded it was for drugs already in existence. Knight Therapeutics won a PRV for a leishmaniosis treatment already in use, while Novartis received one for an existing (but unapproved in the US) malaria drug.
As for access, MSF proposes adding a simple requirement that companies applying for a PRV tell the FDA when and where they plan to register a product.
“At this moment, our access strategy is very very easy to fulfill. It is a question. The program will ask you, "Are you planning to make the product available and where?' If you could not [answer that] before getting the PRV, then you are not interested in serving that community,” Sanjuan said.
First to a vaccine?
The addition of Zika to the PRV program may be too late to really boost R&D by the time any such legislation passed.
As part of its emergency response to the outbreak, the World Health Organization (WHO) has prioritized the development of multiplex diagnostic tests, protective vaccines, and vector control products to limit the spread of mosquitos.
Thirty-one companies are working on diagnostics to identify the Zika virus, which shares similarities to dengue and chikungunya. Another 18 are developing vaccines, but no product has been tested on humans as of yet.
Sanofi, the U.S. National Institutes of Health, and India-based Bharat Biotech may be the farthest along in their development. Bharat has been working on two Zika vaccine candidates for over a year, one of which has progressed to pre-clinical testing in animals.