> ## Content Index > Fetch the complete content index at: https://www.fdaweb.com/llms.txt > Use this file to discover other available public pages before exploring further. # Woodcock Upheld by Califf in Duchenne Drug Appeal - URL: https://www.fdaweb.com/woodcock-upheld-by-califf-in-duchenne-drug-appeal/ - Published: 2016-09-19T12:00:00.000Z - Updated: 2026-09-14T21:32:49.000Z - Author: David McFarland - Tags: Drugs, #legacy-id-D5136852 After surviving an internal staff challenge adjudicated in her favor by FDA commissioner **Robert Califf**, CDER director **Janet Woodcock** made final her decision to approve Sarepta Therapeutics’ Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen) under the agency’s accelerated approval process 9/19\. It’s unprecedented for such a high-level Center decision to be internally appealed and decided by a politically appointed commissioner. The internal challenge was brought before the FDA Scientific Dispute Process Review Board chair and acting chief scientist **Luciana Borio**, who sided with appellant Office of Drug Evaluation 1 director **Ellis Unger**. Unger disagreed with Woodcock’s decision that the NDA’s data met the standard for accelerated approval. The board subsequently asked Califf to review the scientific merits of the case. In a [summary review document](http://www.accessdata.fda.gov/drugsatfda%5Fdocs/nda/2016/206488%5Fsummary%20review%5FRedacted.pdf?ref=fdaweb.com), Califf notes that it is “highly unusual” for a Center director’s application decions to be appealed to the commissioner’s office. After reading Unger’s appeal, Woodcock’s final decision, and the appeal board’s recommendation, Califf said he performed a thorough review of the clinical science and decided to defer to Woodcock’s “judgment and authority.” A key point in the Woodcock and Unger dispute is whether the amount of dystrophin protein produced by eteplirsen is sufficient to be “reasonably likely” to predict clinical benefit, according to the document. Califf concluded that Unger and Woodcock each “exercised reasonable scientific judgment in reaching differing conclusions on whether the effect on dystrophin producttion seen in the studies... reasonably predicts clinical benefit... There is also abundant evidence that Dr. Woodcock heard and read all the scientific evidence, including the detailed views of Dr. Unger and the review team; yet she came to a different conclusion.” Califf also noted that Woodcock in her approval decision is “clearly employing and interpreting the full range of appropriate information, comprising a ‘totality of evidence’ approach in determining that the clinical trials demonstrated an effect on a surrogate endoint that is reasonably likely to predict clinical benefit. Because of the uncertainties in this situation with a surrogate that has not been validated, it is clear that Dr. Woodcock’s decision also utilized the flexibility afforded under the relevant statutory provisions, including consideration of the life-threatening nature of the disease and the lack of alternative treatments.” The appeal board, based on Unger’s complaint, also raised concern about Woodcock’s “level of involvement in the NDA review.” According to the summary document, the board said her “extensive, early involvement in the review process” ... appears to have upended the typical review and dicision-making process.” It further cautioned that “care should be taken to avoid the appearance of interfering with the integrity of scientific reviews at the lower levels of a Center.” The board concluded that “Dr. Woodcock herself was the one who conducted that review and resolved the conflict in her own favor.” Califf did not falter in his support of Woodcock. He endorsed her “hands on” approach during her entire career at FDA. “She is well-known for interacting with staff at all levels and expressing her opinions,” he said in the summary. “This development program may represent a point of particular focus for Dr. Woodcock with the result that her involvement was more intensive than usual and correspondingly had an effect upon the review team, but such a focus does fit within a longstanding management approach.” Califf concluded that Woodcock did not deviate from her responsibilities, nor did she succumb to pressures from the patient community, the public or others. “Further, I do not find the general pattern of discourse and involvement to be atypical for Dr. Woodcock’s management of the Center, nor do I find that her conduct was in conflict with the job requirements for the Center directors at the FDA.” As for the accelerated approval, this is the first drug approved to treat patients with Duchenne. The drug is indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13% of the DMD population. “Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct after approval,” Woodcock said in a [news release](http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm?ref=fdaweb.com). The approval comes 10 days after the departure of CDER Division of Neurology Products clinical team leader **Ronald Farkas**, who joined clinical research organization Parexel 9/9\. Farkas was one of the harshest critics of Sarepta’s NDA during an April advisory committee meeting that voted 7 to 6 ([see story](https://www.fdaweb.com/fda-panel-split-vote-not-encouraging-for-duchenne-drug/)) that the company did not provide substantial evidence from adequate and well controlled studies that the drug induces production of dystrophin to a level that is reasonably likely to predict clinical benefit in patients. In June, the company agreed to an agency request that it provide dystrophin data, as measured by western blot, from biopsies already obtained from an ongoing confirmatory study of eteplirsen (PROMOVI). The company said at the time that it planned to submit data from 13 patient biopsy samples, at baseline and week 48, to the agency within a few weeks. In a [statement](http://investorrelations.sarepta.com/phoenix.zhtml?c=64231&p=irol-newsArticle&ID=2175522&ref=fdaweb.com), Sarepta said it expected this would “facilitate a prompt decision on the NDA by the agency.” Eteplirsen is designed to address the underlying cause of Duchenne’s by restoring the dystrophin messenger RNA (mRNA) reading frame, and enabling the production of a shorter, functional form of the dystrophin protein, according to the company.