A Tale of Two Drug Approvals

At the Food and Drug Administration (FDA), promising medications and products often languish on the sidelines despite powerful evidence of safety and efficacy. That’s why agency watchers were pleasantly surprised on October 21 when the FDA approved Trikafta, a novel triple combination therapy to treat cystic fibrosis. According to Carolyn Y. Johnson, a reporter with The Washington Post,  “The data, being unveiled… at a national conference in Tennessee and simultaneously published in two leading medical journals, was so persuasive that the Food and Drug Administration last week approved the three-drug combination… five months ahead of the agency’s deadline.”

But there’s a reason why everybody was so surprised to see this expedited approval. The FDA doesn’t have the best track record in approving promising medications quickly, and the agency often forces producers to go back to the drawing board due to minor issues.

By all accounts, Trikafta’s approval is good news for the tens of thousands of cystic fibrosis sufferers in the U.S. The medication’s producer expects that the drug will be able to treat 9 in 10 sufferers of the disease and insurers are already talking about reimbursement.

However, a few months ago, drug maker AstraZeneca expected a similarly positive outcome for their experimental triple combination inhaler PT010 which is to be used for the treatment of chronic obstructive pulmonary disease (COPD). There’s plenty of evidence that the inhaler, which has already been approved in Japan, reduces flareups for COPD and improves lung function for sufferers of the disease. Nonetheless, the FDA sent AstraZeneca a Complete Response Letter (read: rejection) on October 1. COPD sufferers were left in the lurch as the drug’s producer must now submit additional evidence to the FDA and hope for a better outcome.

Examining the respective cases of Trikafta and PT010, agency watchers can see how different regulatory approaches within the same agency can lead to vastly different outcomes. If regulators treated Trikafta as they would a typical drug, they’d wait for compelling evidence to be formally logged with the FDA, and even then, they might nitpick the data or send a Complete Response Letter and force the producer to subtly tweak their clinical trials. But, bureaucrats evaluating the medication’s case had eyes and ears on the ground and were open-minded enough to green-light the medication even if the latest evidence wasn’t submitted to the FDA itself.

In contrast, the agency ignored new and compelling evidence for PT010 released shortly after AstraZeneca submitted their application to the FDA. On August 28, AstreaZeneca released the results of late-stage ETHOS trial, which provided the most compelling evidence to date of the medication’s effectiveness. But, because the information didn’t have a regulatory filing number, the agency ignored the easily-accessible evidence and instead chose to evaluate weaker evidence that had been submitted with the company’s application.

This might be acceptable behavior for a university dealing with a prospective student that turned in an incomplete application. In contrast, however, the FDA has a unique responsibility to approve game-changing medications in a timely manner, as millions of lives hang in the balance. Too often the FDA neglects that responsibility, and as a result, the drug approval process has become increasingly costly and time-consuming. The agency’s approach toward Trikafta is a promising one, and hopefully part and parcel of a change in regulatory philosophy. Only time will tell, but let’s hope so for the sake of countless Americans suffering from curable diseases.