FDA Leadership Ignores Science, Approves Ineffective Drug

On Sept. 19, 2016, the Food and Drug Administration (FDA) approved eteplirsen (EXONDYS 51) — the first drug approved for treating Duchenne muscular dystrophy (DMD)[1] — despite a disturbing lack of evidence that the drug is actually effective. The approval decision ultimately was made by Dr. Janet Woodcock, longtime director of the FDA’s Center for Drug Evaluation and Research (CDER), over the strong objections of CDER scientific experts who reviewed the new drug application for eteplirsen.[2]

Sarepta Therapeutics, the maker of eteplirsen, submitted data to the FDA from three very small clinical trials involving a total of 25 subjects with DMD. FDA staff, including Woodcock, agreed that there were “[m]ajor flaws in both the design and conduct” of these trials.[3] Moreover, the trials found no meaningful improvement in subjects’ physical performance and only minuscule increases in their levels of the muscle protein that is deficient in DMD and that the drug is intended to boost. As a result, a team of FDA scientific experts concluded that the trials failed to provide substantial evidence that the drug is effective — the legal standard for approving new drugs since 1962 — and recommended against approval of the drug.

Dr. Ellis Unger, the senior FDA official who supervised the team of scientists that reviewed the data on eteplirsen, concurred with the team’s assessment, as did his supervisor, the FDA’s acting chief scientist and the majority of an FDA advisory committee that reviewed the drug.[4]

Despite the overwhelming opposition to the approval of eteplirsen, Woodcock overruled the FDA’s scientific experts and decided to approve the drug. In a highly unusual move, Unger formally appealed Woodcock’s decision to FDA Commissioner Robert Califf. But Califf deferred to Woodcock, allowing the approval to go forward.

In his appeal to Califf, Unger argued, “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. I argue that this would be unethical and counterproductive.”[5] Alluding to intense pressure on the FDA from patients and Congress to approve eteplirsen, Unger further noted, “Approval of this [drug] would send the signal that political pressure and even intimidation – not science – guides FDA decisions, with extremely negative consequences.”[6]

Woodcock’s decision to overrule so many agency experts represents a dangerous, unprecedented capitulation to pressure from politicians and patients and a stunning disregard of scientific evidence. Her action eviscerates the FDA’s long-standing (but, under Woodcock, already declining) approval standards for new drugs, threatens public health and demonstrates that she is unfit to serve as CDER director, a position she has held for almost 20 years.

References

[1] Food and Drug Administration. FDA news release: FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. September 19, 2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm. Accessed September 20, 2016.

[2] Food and Drug Administration. Summary review for eteplirsen. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206488_summary%20review_Redacted.pdf. Accessed September 20, 2016.

[3] Ibid.

[4] Food and Drug Administration. Summary minutes of the Peripheral and Central Nervous System Drugs Advisory Committee meeting. April 25, 2016. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PeripheralandCentralNervousSystemDrugsAdvisoryCommittee/UCM509870.pdf. Accessed September 20, 2016.

[5] Food and Drug Administration. Summary review for eteplirsen. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206488_summary%20review_Redacted.pdf. Accessed September 20, 2016.

[6] Ibid.