Pharma Can Buy Hasty FDA Reviews of New Drugs

By SAM URETSKY

The May 2016 issue of the Journal of Health Economics carried the results of a study by the Tufts Center for the Study of Drug Development, which concluded that the costs of bringing a new drug to market came to $2.558 billion. If the Food and Drug Administration insisted on post marketing studies, the price went up to $2.87 billion over the market life of the drug.

The nature of our economy leads drug companies to want to get their drugs on the market as quickly as possible, and this leads to a number of programs intended to speed up the Food & Drug Administration review process. The first program to speed up the review, from the traditional 10 months to 6 months. In 1992, and the Prescription Drug User Act (PDUFA). Under this act, the FDA developed a two-tier system, Standard Review and Priority Review. A Priority Review would be given if a drug seemed to offer significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

Also in 1992 the FDA instituted the Accelerated Approval regulations. These regulations allowed drugs for serious conditions that filled an unmet medical need to be approved based on a surrogate endpoint. A surrogate endpoint would be a change in some laboratory value that would be associated with a therapeutic improvement. For example, a drug that lowers cholesterol would be assumed to reduce the risk of heart attacks and strokes without the need to wait to see if there really is a reduction in the number of heart attacks. In 2012, Congress passed the Food and Drug Administration Safety Innovations Act (FDASIA). to allow the FDA to offer accelerated approval for drugs that fill an unmet medical need on whether the drug has an effect on a surrogate has an effect on a surrogate endpoint.

Besides these higher priority reviews the FDA can offer Fast Track review for drugs that seem to meet an important need and Breakthrough Therapy which offers all the benefits of accelerated approval along with special consideration by the Food & Drug Administration which will offer advice on how to speed up the approval process.

Finally another feature of PDUFA allowed the FDA to charge a user fee for having a drug reviewed. According to Forbes magazine, “The actual user fee charged to each company filing an NDA in 1995 was $208,000. In 2014, the user fee will be $2,169,100. If you assume that as many as 50 NDAs are filed in a year, Congress is passing on $100 million of FDA funding costs to the industry.” A review of the FDA budgets from 2008 to the present shows appropriations of that while the agency received roughly the amount it requested in 2008 and 2009, but since then has been cut by approximately $100 million along with and additional $200 million under the sequestration of 2013.

The effort to accelerate approvals may have a downside. In 2008 the New England Journal of Medicine published a report saying “report that new molecular entities (NMEs) approved in the two months before the first review deadlines established under the Prescription Drug User Fee Act (PDUFA) showed a higher rate of postmarketing safety problems — as measured by safety-based withdrawals, new black-box warnings, or dosage-form discontinuations — than drugs approved at any other time. (The authors) suggest that pressure to respond within the allotted time leads to poorer decision making.”

In 2017, the FDA set a record with 46 approvals of new molecular entities (“NMEs”). While the FDA claims to have the same standards as in the past, Bloomberg Business News has reported on two drugs which were given wider approval than seemed justified by the reported studies, including one that was never even tested against a placebo control.

MedCity News reported on problems with several other approvals. One was Emflaza (deflazacort) for Duchenne muscular dystrophy submitted by Marathon Pharmacueticals. “The exact same drug had been available overseas for decades at a cost of around $0.60 per dose. Marathon slapped an $89,000 price tag on its US version.“ The drug company backed down after extensive press coverage and a letter signed by Senator Bernie Sanders and Rep. Elija Cummings.

Radicava (edaravone) for amyotrophic lateral sclerosis (ALS) was approved on the basis of a single, six month Japanese study. Admittedly ALS, also known as Lou Gehrig’s Disease, is rapidly progressive and there have been no new treatments in 20 years, but in this case the manufacturer hadn’t even applied for United States approval and there are no reported plans for post marketing studies,

September, the FDA granted accelerated approval to Exondys 51 (Exondys, or eteplirsen), for the treatment of Duchenne muscular dystrophy (DMD). While there is a clear need for more treatments for DMD, Exondys was approved over the advice of the agency’s staff and advisors. One FDA committee member, was quoted as saying Exondys lowers the agency’s evidentiary standard for drug effectiveness “to an unprecedented nadir.”

The US Food & Drug Administration has been the world standard for consumer protection. Dr, David Kessler, who was FDA Commissioner under Presidents George H.W. Bush and Bill Clinton said. “We are the envy of the world because our honey is our honey. Our foods are not laced with pesticides. Our drugs work.” That was then.

Sam Uretsky is a writer and pharmacist living in New York. Email sdu01@outlook.com.

From The Progressive Populist, Febuary 15, 2018

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