Senator Marco Rubio’s essay criticizing the FDA for failing to approve eteplirsen, an investigational drug for Duchenne muscular dystrophy made by Sarepta Therapeutics, highlights a glaring misunderstanding of the drug approval process. Public appeals like Rubio’s and those made by Duchenne families are perfectly appropriate and make for interesting public theater. But they have essentially zero effect on the FDA’s decision-making cascade.

As a former FDA medical officer and senior medical analyst, as well as a former investigational medicine research scientist at Pfizer, I don’t always agree with the regulatory decisions the FDA makes. However, I do support the time-tested process for approving new drugs.

The FDA’s mission requires that it be sure that the drugs it approves are safe and effective. To do this it needs concrete data from controlled clinical data that prove the drug works better than (or, in some cases, at least as well as) an existing therapy. Emotional appeals from the public or from politicians do nothing to establish the parameters of safety or efficacy.

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I can tell STAT readers a secret about the “public speaking” portion of FDA advisory committee meetings: It is all for show. I can recall my FDA supervisors and colleagues checking their emails, doodling, texting, and the like to avoid listening to individuals who would often travel great distances to pour out their hearts to the advisory committee and FDA reviewers, literally begging them to approve a new drug.

The clinical and regulatory review process is extremely complicated and is — or should be — 100 percent based on the safety and efficacy outcomes that emerged from the clinical trial. Even experienced pharmacologists and physicians need years of experience to fully appreciate the complexity of the process. That’s why drug-approval decisions are best left to the experts.

Right-to-try” legislation makes sense for people who don’t understand the complexities of the drug development process. As a rare Republican working at the FDA and a generally politically conservative person, I am all for more freedom and less government intervention — but not when it comes to drug approval. The truth is, I am not quite ready to entrust the general public (or, for that matter, a senator with no scientific or clinical background) to circumvent the FDA through “right-to-try” and to make independent recommendations regarding clinical pharmacology, pharmacogenomics, biomarkers, and long-term drug safety.

I understand Senator Rubio’s desire to advocate for drugs for rare diseases. But he ought to leave the complexities of drug evaluation and review to experienced FDA scientists.

It’s easy to see why the public, and even politicians like Senator Rubio, are confused by the FDA’s seemingly likely decision to reject eteplirsen in light of several other highly controversial FDA approvals.

For example, last year the FDA gave the green light to flibanserin (Addyi), a drug to treat low sexual desire in women. Although this is a problem for some women, it does not represent a big public health issue, is not debilitating or fatal, and has significant safety issues. What’s more, flibanserin doesn’t work for the vast majority of women, positively affecting only between 8 and 13 percent of those who take it. In addition, flibanserin has potentially fatal drug-drug interactions with alcohol and the most commonly prescribed antibiotics and antifungals currently on the market. Some prominent national health women’s groups have voiced their opposition to its approval.

In contrast, Duchenne muscular dystrophy affects children and young people, robs them of an active life, and is always fatal. Even if eteplirsen, the new drug for Duchenne, has both safety and efficacy issues, the decision not to approve it, in light of the decision to approve flibanserin, has left many people, including most clinical scientists, scratching their heads in confusion.

The FDA’s impending decision isn’t necessarily a death sentence for eteplirsen or for a similar Duchenne drug made by PTC Therapeutics, which was also rejected. A third competitor, BioMarin Pharmaceutical, has just abandoned all of its most advanced Duchenne projects. Many drugs currently on the market required multiple FDA advisory committee meetings, or weren’t approved on the first or even the second review. In fact, flibanserin was one of those — it took three separate submissions to finally gain FDA approval.

If these companies truly believe that their investigational drugs for Duchenne hold clinical promise, they should stick by their compounds and do whatever FDA-required clinical testing is needed to fully comply with the FDA’s requirements for approval. That’s what the makers of flibanserin did, and they were eventually able to convince advisory committees and the FDA, in spite of what can only be described as very poor efficacy and safety profiles.

My advice to these companies: Stop the public relations campaigns, which do nothing to sway the FDA’s decision making process. My advice to my fellow Republican, Senator Marco Rubio: If you are upset with the way the FDA does business, create new legislation to change how it works. Or maintain the status quo and leave the new drug reviews and approvals to FDA scientists, like the ones who approved flibanserin.

David Gortler, PharmD, has two decades of drug development experience. He has been an investigational medicine research scientist at Pfizer, a medical officer/senior medical analyst with the FDA, and a professor of pharmacology at Yale University School of Medicine and Georgetown University School of Medicine. He is now a drug safety expert and FDA policy expert with the consulting group FormerFDA.com.

  • Oh, and one more, and this one is actually something a lot of advisory committee members don’t understand, either (so, you’re not alone): if the drug does not get approval, the company will likely go bankrupt before full approval, and this affects the timeline of the drug. Just take a look at the Clovis Oncology outcome. The ORR was based on a small subset of data, and it went from 58% to 32% confirmed to 45% on May 12. But by then it was too late because without revenues from accelerated approval, Clovis would not have the money to finish the very long and very expensive trials.

    To be on an advisory committee meeting, or more importantly, working in the FDA, and not understand the financial repercussions of approval decisions is something that just shouldn’t happen.

    • Oh, well then it only makes sense to approve the drug on limited data before the poor, helpless for-profit pharmaceutical company runs out of money!

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