R&R – Reachout and Rebuild

I have previously warned about defanging the FDA.  The FDA (Federal Drug Administration) has saved this country from major catastrophies like the malformations  (see title image) caused by thalidomide taken during pregnancy. This reached worldwide epidemic numbers in the 1950s but the US was largely spared because the FDA did not approve the drug.

In last week’s address to Congress Trump did it again. He wants to do away with FDA regulations.  It is a terrible idea.  Here is a great article on the subject by David Hilzenrath. It appeared on March 3rd on pogo.org.

In his address to Congress this week, President Trump argued that slashing regulatory restraints at the Food and Drug Administration (FDA) could unleash medical miracles. To make his case, he pointed to 20-year-old Megan Crowley, who was expected to die years ago until her father helped develop a drug for her rare disease.

“[O]ur slow and burdensome approval process at the Food and Drug Administration keeps too many advances, like the one that saved Megan’s life, from reaching those in need,” Trump said.

Crowley’s story is a moving one, but a closer look at that story and at the FDA more generally could point to very different conclusions.

The FDA approved Myozyme, the drug that saved Crowley from Pompe disease, in April 2006, nine months after drug-maker Genzyme submitted its application to market the drug. That illustrated a sharp decline over recent decades in the amount of time the FDA takes to review new drugs.

In 1993, the approval time was typically 19.1 months for drugs and biologic products involving a new medicine, according to FDA data. As of 2016, the median time to approval was 7.8 months, the FDA reported.

The FDA approved Myozyme despite finding that the drug itself could hurt people. The label the FDA negotiated in 2006 prominently warns of potentially “life-threatening” side-effects, adding: “BECAUSE OF THE POTENTIAL FOR SEVERE INFUSION REACTIONS, APPROPRIATE MEDICAL SUPPORT MEASURES SHOULD BE READILY AVAILABLE WHEN MYOZYME IS ADMINISTERED.” The agency’s approval seemed to reflect the philosophy that, for patients suffering from a terrible and otherwise incurable disease, a chance at life—or a chance at an improved quality of life—can be worth potentially deadly risks.

An internal FDA memo dated April 27, 2006—the day before the FDA approved Myozyme—shows why it is important for the FDA to scrutinize research on experimental drugs before approving them.

Under the heading “Outstanding Safety Issues,” the memo says an FDA review team “has come to have concerns that the applicant applied an overly narrow interpretation as to what safety information should be presented to the FDA.”

“The review team also has serious concerns that significant safety information that should have been clearly identified, analyzed, and discussed” in a safety summary “was effectively obscured in the way it was presented in the application.” For example, according to the memo, the FDA learned from “a third party” that a patient chose to stop treatment after a reaction to the drug led to a stay in an intensive care unit.  The application to the FDA apparently did not explain that that patient discontinued use of the drug due to an adverse event, the memo says.

“It is the opinion of the review team that in order to evaluate the safety of this product adequately it will be necessary to obtain additional information from the applicant, and additional time will be needed to assess the significance of the new information,” the memo says.

As noted, the drug was approved the next day.

Though many drugs undergo clinical testing in thousands of patients before the FDA approves them, the testing of Myozyme reflected the fact that Pompe is a rare disease. Margaret Hamburg, a former FDA commissioner, cited the agency’s approval of Myozyme as evidence of the agency’s “considerable regulatory flexibility.”

“[I]n 2006 we approved a treatment for Pompe Disease—a rare genetic disorder that causes debilitating muscle weakness—on the basis of a single pivotal study of 18 patients,” Hamburg said in a 2011 speech.

Does Genzyme think the FDA’s handling of Myozyme was “slow and burdensome?” We asked a company spokeswoman that question by email Wednesday. In a reply on Thursday, the spokeswoman, Lisa Clemence, declined to comment. Efforts to reach biotech executive John F. Crowley, the father of Megan Crowley, were unsuccessful.

Years after Myozyme won FDA approval, the FDA issued a public warning that Myozyme and other Genzyme products could be contaminated. “The foreign particles, believed to be found in less than 1% of products based on product lots assessed to date, include stainless steel fragments, non-latex rubber from the vial stopper, and fiber-like material from the manufacturing process and could potentially cause serious adverse events in patients,” the FDA warned. Again, the FDA showed forbearance, allowing the potentially compromised drugs to remain on the market.

“The Agency is acutely aware of the critical need for patients to have continued access to these important products,” the FDA said.

In an article about Trump’s FDA critique, Julia Belluz of Vox wrote this week that the major impediment isn’t getting the FDA to approve new medicines; it’s the scientific difficulty inherent in discovering or devising those medicines.

“It’s not the FDA that gets in the way of innovation—it’s the limits of our knowledge,” the article said.

As recent history and reporting by the Project On Government Oversight show, the public interest may be endangered by an FDA that places too little emphasis on the safety and efficacy of the drugs it is reviewing, by haste and lack of thoroughness, and by the pharmaceutical industry’s drive for potentially looser drug approval standards.

Last year, the FDA approved a $300,000-a-year drug for another devastating disease—Duchenne Muscular Dystrophy—despite having concluded that there was no good evidence the drug actually worked. As the head of the FDA at the time wrote, the drug’s “clinical benefit has not yet been established.”

A top FDA scientist who argued against the drug’s approval expressed himself more bluntly.

“By allowing the marketing of an ineffective drug, essentially a scientifically elegant placebo, thousands of patients and their families would be given false hope in exchange for hardship and risk,” Ellis F. Unger, director of the FDA’s “Office of Drug Evaluation – I,” wrote in a July memo.

“I argue that this would be unethical and counterproductive,” Unger wrote. “There could also be significant and unjustified financial costs—if not to patients, to society.”

It’s understandable that desperate patients and their families might seize upon any chance of a cure or treatment, no matter how slim. But approving drugs on that basis entails tradeoffs. As POGO has reported, it could not only harm patients but also spur wasteful spending by consumers, private health insurers, and government programs.

Approving unproven drugs, or approving drugs on the basis of unscientific evidence, could be tantamount to writing a blank check to drug companies, contributing to unsustainable health-care costs.

It could divert spending from more promising treatments, and it could dilute economic incentives for researchers and pharmaceutical firms to come up with cures that actually work and work safely instead putting patients at greater risk.