Priority review (FDA)

Priority review, also known as the priority review voucher, is an expedited review granted by the United States Food and Drug Administration (FDA) to the developer of a treatment for neglected diseases and rare pediatric diseases.

In 2007 Senators Sam Brownback (R-KS) and Sherrod Brown (D-OH) sponsored an amendment to the FDA Amendments Act of 2007. President George W. Bush signed the bill in September 2007.

The rare pediatric disease system was developed and championed by Nancy Goodman and Kids v Cancer as the Creating Hope Act in 2012 as part of the FDA Safety and Innovation Act as 21 U.S.C. 360ff. The Creating Hope Act built upon the tropical disease system and made certain corrections including a shorter notification to the FDA before exercising a voucher, a designation system so that early in the drug development cycle, sponsors may use the possibility of earning a voucher in their valuation of their company; a requirement of a marketing plan and reporting of marketing; and indefinite transferability of the voucher (see www.kidsvcancer.org).

Summary

The priority review is an incentive for companies to invest in new drugs and vaccines for neglected tropical diseases and rare pediatric diseases.

Priority review

Prior to approval, each drug marketed in the United States must go through a detailed FDA review process. In 1992, under the Prescription Drug User Fee Act (PDUFA), FDA agreed to specific goals for improving the drug review time and created a two-tiered system of review times – Standard Review and Priority Review.

Standard Review is applied to a drug that offers at most, only minor improvement over existing marketed therapies. The 2002 amendments to PDUFA set a goal that a Standard Review of a new drug application be accomplished within a ten-month time frame.

A Priority Review designation is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. A Priority Review means that the time it takes FDA to review a new drug application is reduced. The FDA goal for completing a Priority Review is six months.

Priority Review status can apply both to drugs that are used to treat serious diseases and to drugs for less serious illnesses.

The distinction between priority and standard review times is that additional FDA attention and resources will be directed to drugs that have the potential to provide significant advances in treatment. Such advances can be demonstrated by, for example:

evidence of increased effectiveness in treatment, prevention, or diagnosis of disease; elimination or substantial reduction of a treatment-limiting drug reaction; documented enhancement of patient willingness or ability to take the drug according to the required schedule and dose; or evidence of safety and effectiveness in a new subpopulation, such as children. A request for Priority Review must be made by the drug company. It does not affect the length of the clinical trial period. FDA determines within 45 days of the drug company’s request whether a Priority or Standard Review designation will be assigned. Designation of a drug as “Priority” does not alter the scientific/medical standard for approval or the quality of evidence necessary.

Mechanism

The statute authorizes the FDA to award a priority review voucher to the sponsor (manufacturer) of a newly approved drug or biologic that targets a neglected tropical disease or a rare pediatric disease. The provision applies to New Drug Applications (NDAs), Biological License Applications (BLAs) and 505(b)(2) applications. The voucher, which is transferable and can be sold, entitles the bearer to a priority review for another product.

Under current Prescription Drug User Fee Act targets, the FDA aims to complete and act upon reviews of priority drugs within six months instead of the standard ten-month review period. Actual FDA review timelines, however, can be longer than the target PDUFA review periods, particularly for new products that haven’t previously been approved. Economists at Duke University, who published on this concept in 2006, estimated that priority review can cut the FDA review process from an average of 18 months down to six months, shortening by as much as a full year the time it takes for the company’s drug to reach the market.[1]

In 2015, a pediatric cancer drug developed by United Therapeutics sold for $350 million. At this level, the voucher would be expected to offset the substantial investment and risk required for discovery and development of a new treatment for a neglected disease. If the time saved from gaining a priority review is much shorter, however, the value of the voucher will be significantly less. In fact, in 2006, median standard review times were 12 months, suggesting that a voucher could cut six months from the standard review period.

An intangible benefit of the voucher is the value created for a company if the faster review provides them "first mover advantage," allowing the voucher holder's product to be introduced ahead of a similar, competing product. By taking advantage of existing market forces, patients in the developing world can have faster access to lifesaving products that may not otherwise be developed. And sponsors of neglected disease drugs can be rewarded for their innovations.[2]

Companies that use the voucher will be required to pay a supplemental priority review user fee to ensure that the FDA can recoup the costs incurred by the agency for the faster review. The additional user fee also aims to ensure that the new program will not slow the progress of other products awaiting FDA review.

Diseases targeted

The tropical diseases that will benefit include the following:[3]

The amendment

The amendment can be found on page 150 of the Food and Drug Administration Amendments Act of 2007.[3]

News and reaction

According to Bill Gates,[4]

"But some of the highest-leverage work that government can do is to set policy and disburse funds in ways that create market incentives for business activity that improves the lives of the poor. Under a law signed by President Bush last year, any drug company that develops a new treatment for a neglected disease like malaria or TB can get priority review from the Food and Drug Administration for another product they've made. If you develop a new drug for malaria, your profitable cholesterol-lowering drug could go on the market a year earlier. This priority review could be worth hundreds of millions of dollars."
— Bill Gates at the World Economic Forum in Davos in 2008.

Limitations

First, for tropic disease drug development, the priority review voucher might be too small. This is likely not the case for pediatric rare diseases. Tropical diseases with incredible burdens might merit more resources. The Advance Market Commitment, proposed by Michael Kremer and colleagues, calls for creating a $3 billion market for neglected diseases with high burdens, such as malaria, tuberculosis, and HIV/AIDS.

Second, the priority review voucher might be too large, if it rewards research which would have been done anyway, or research with low value. Aidan Hollis of the University of Calgary notes that "firms which are developing very profitable products will be rewarded even more". While some treatments for neglected diseases are lucrative, this is generally not the rule, which is why the diseases are neglected.

Third, the priority review voucher encourages innovation, but does not pay for access to existing therapies. Funding from governments or foundations might be needed to purchase treatments for poor people. Aidan Hollis of the University of Calgary has commented that the proposal does not address "the access problem, but helps to increase incentives through creating distortions in markets in developed countries".

Fourth, the priority review voucher might tie up FDA resources. Fortunately, however, the pediatric PRV includes an extra fee paid by manufacturers to the FDA and requires that voucher bearers provide FDA with 90 days' notice before using a voucher.

Fifth, priority review might not be safe. Priority review should not, however, be confused with accelerated approval or fast track. Priority review does not omit safety or efficacy studies or require approval within a given time frame. It sets a target of 6 rather than 10 months for FDA review. Nevertheless, if the FDA feels pressure to meet deadlines faster, it might be more likely to err. Carpenter and colleagues (2008) report that new molecular entities approved in the two months before the first review deadlines showed a higher rate of postmarketing safety problems than drugs approved at other times.[5] Nardinelli and colleagues (2008) of the FDA, however, wrote that they were not able to replicate the findings and that the findings might be driven by HIV-AIDS therapies.[6] Following the Nardinelli piece, Carpenter acknowledged several errors in their data set and demonstrated errors in the FDA's and Nardinelli's data; Carpenter and colleagues report that the original associations between last-minute approvals and safety problems hold.[6]

Extension to Europe

Writing in The Lancet, David Ridley and Alfonso Calles Sánchez proposed extending the voucher to the European Union. The proposed EU voucher would provide priority regulatory review through the European Medicines Agency, as well as accelerated pricing and reimbursement decisions by EU member states.[7]

Extension to rare pediatric diseases

In 2012, President Obama signed into law the FDA Safety and Innovation Act which includes Section 908 the "Rare Pediatric Disease Priority Review Voucher Incentive Program".[8] The act extends the voucher program to rare pediatric diseases, but only on a trial basis. One year after the third pediatric voucher is awarded, no other pediatric vouchers may be awarded. The extension to rare pediatric diseases was championed by Nancy Goodman of Kids v Cancer.

The pediatric voucher program includes several changes that had been sought for the neglected-disease voucher program, but apply only to pediatric vouchers. First, the pediatric treatment developer can ask the FDA in advance for an indication of whether the disease qualifies as a rare, pediatric disease. Second, the pediatric voucher can be transferred an unlimited number of times, whereas the neglected-disease voucher can only be transferred once. Third, the pediatric voucher user needs to notify FDA 90 days prior to using the voucher, rather than 1 year for the neglected-disease voucher. Fourth, the pediatric voucher winner risks having the voucher revoked if the treatment is not marketed within a year. Fifth, the pediatric voucher winner must report to FDA about use of the pediatric treatment within five years of approval.

Extension to Ebola virus

In December 2014, the Senate approved a bill that would add the Ebola virus to the Priority Review Voucher List.[9] The bill, S. 2917—Adding Ebola to the FDA Priority Review Voucher Program Act, was introduced by Senator Tom Harkin on November 12, 2014. President Obama signed it on December 16, and it became Public Law 113-233.[10] Forty-five Senators cosponsored the bill (26 Democrats and 19 Republicans).[11]

Companies that develop Ebola drugs and take advantage of the priority voucher must pay the FDA the cost the FDA incurs to speed up the drug review process.[12]

On a technical level, S. 2917 added “Filoviruses” to the priority review list. The Ebola virus is a type of Filovirus. According to the Congressional Budget Office, enactment of the law does not have an effect on the federal budget.[12]

Lucrative secondary market

According to Forbes journalist Tim Worstall, the priority review voucher emerged as a "lucrative secondary market."[13] In an article in the Wall Street Journal concerns were raised about the sale of these vouchers[14] that "require the FDA to shorten its decision deadline to six months from the standard 10 months—potentially giving companies an extra four months’ worth of sales. The voucher doesn’t guarantee the FDA will approve the drug."[14] In August 2015 United Therapeutics sold its pediatric-rare disease FDA priority review voucher that it had received for the development of Unituxin to AbbVie for $350 million.[13]

In July 2014, Regeneron and Sanofi announced that they had purchased a priority review voucher that BioMarin had won for a recent rare disease drug approval for $67.5 million; the voucher cut four months off the regulatory review time for alirocumab and was part of their strategy to beat Amgen to market with the first approval of a PCSK9 inhibitor.[14][15][16]

See also

References

  1. ↑ Ridley DB, Grabowski HG, Moe JL (2006). "Developing drugs for developing countries". Health Aff (Millwood). 25 (2): 313–24. doi:10.1377/hlthaff.25.2.313. PMID 16522573.
  2. ↑ http://www.bvgh.org/documents/Brownback-BrownanalysisFINAL.pdf
  3. 1 2 H.R. 3580
  4. ↑ Bill Gates - Bill & Melinda Gates Foundation
  5. ↑ Carpenter D, Zucker EJ, Avorn J (March 2008). "Drug-review deadlines and safety problems". N. Engl. J. Med. 358 (13): 1354–61. doi:10.1056/NEJMsa0706341. PMID 18367738.
  6. 1 2 Nardinelli C, Lanthier M, Temple R (July 2008). "Drug-review deadlines and safety problems". N. Engl. J. Med. 359 (1): 95–6; author reply 96–8. doi:10.1056/NEJMc086158. PMID 18596282.
  7. ↑ Ridley DB, Sánchez AC (September 2010). "Introduction of European priority review vouchers to encourage development of new medicines for neglected diseases". Lancet. 376 (9744): 922–7. doi:10.1016/S0140-6736(10)60669-1. PMID 20833303.
  8. ↑ "Section 529 Rare Pediatric Disease Priority Review Voucher Incentive Program, Public Law 112-144" (PDF). Public Law. 9 July 2012. Retrieved 19 November 2015.
  9. ↑ Daw, Daniel (5 December 2014). "Senators praise passage of faster Ebola review by FDA". BioPrepWatch. Chicago, Illinois. Retrieved 23 March 2015.
  10. ↑ "Summary: S.2917 — 113th Congress (2013-2014)". Congress.gov. Washington, D.C.: U.S. Library of Congress. Retrieved 23 March 2015.
  11. ↑ "Cosponsors: S.2917 — 113th Congress (2013-2014)". Congress.gov. U.S. Library of Congress. Retrieved 23 March 2015.
  12. 1 2 "S. 2917, Adding Ebola to the FDA Priority Review Voucher Program Act; Cost Estimate". Congressional Budget Office. 25 November 2014. Retrieved 23 March 2015.
  13. 1 2 Worstall, Tim (20 October 2015). "The Economic Proof That The FDA's Drug Regulation Makes Us All Poorer". Forbes. Retrieved 19 November 2015.
  14. 1 2 3 Loftus, Peter (1 November 2015). "Drug Makers Buy Pricey Vouchers to Speed Products to Market". Wall Street Journal. Retrieved 19 November 2015.
  15. ↑ John Carroll (July 30, 2014), "Sanofi, Regeneron pay $67M for a shortcut in the blockbuster PCSK9 race with Amgen", FierceBiotech
  16. ↑ Ron Winslow; Joseph Walker (July 30, 2014), "Drug Firms Buy $67.5 Million Voucher to Speed FDA Review", Wall Street Journal

External links

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