Dive Brief:
- The Food and Drug Administration released a report late last week highlighting 22 case studies of drugs which had cleared Phase 2 studies with promising results, only to fail in Phase 3.
- Designed to be illustrative of the challenges of drug development, the report comes as several critics of the FDA's approval standards are rumored candidates to lead the FDA under the Trump administration.
- Jim O'Neill, Balaji Srinivasan and Joseph Gulfo have all been reported to be in the running for FDA chief in recent months, and each have expressed views in the past criticizing the FDA for moving too slowly. The FDA's report, while not necessarily directed at the candidates themselves, serves as a reminder of the importance of later-stage efficacy studies.
Dive Insight:
Among the 22 drugs considered by the report are several candidates which had blockbuster expectations going into Phase 3 testing.
Pfizer, for example, reportedly spent $800 million to test its cardiovascular disease candidate torcetrapib, enrolling 15,000 patients in a Phase 3 study after promising biomarker results in Phase 2. The drug proved to be ineffective and increased the likelihood of both major adverse cardiac events and death from any cause.
Another 6 drugs failed to demonstrate both safety and efficacy in Phase 3, while 14 others fell short on efficacy grounds.
The report gives ammunition to defenders of the FDA's current regulatory approach, which could come under scrutiny if some of the current rumored candidates get the nod from President Trump.
O'Neill, for example, suggested in a 2014 speech that drugs could be approved on safety and preliminary efficacy and then further tested while on the marketplace.
Srinivasan, who co-founded a diagnostic company, has tweeted criticisms of the agency (now taken down). In August, Srinivasan tweeted, "Before the FDA, scientists were able to take insulin from bench to bedside in two years," suggesting the agency has slowed new medicines from getting to patients. Other tweets acknowledged the goal of regulation but argued delay in letting promising new treatments through has lead to patient deaths.
Joseph Gulfo, a vocal critic of the agency, also is rumored to be on Trump’s shortlist for FDA commissioner, according to Stat News, as is former FDA staffer Scott Gottleib.
The FDA's report recognizes that rapid advances in biomedical sciences have improved the predictive capacity of phase 1 and phase 2 trials. But the 22 cases detailed "demonstrate that phase 2 results can inaccurately predict safety and/or effectiveness for medical products in a wide range of diseases and patient populations."
And, as a result of the failed Phase 3 tests, "patients outside of clinical trials were not subjected to drugs that would not benefit them or to the risk of unnecessary serious toxicities, and did not suffer unnecessary financial expenditures," the FDA authors wrote.