Will Hunt­ing­ton’s dis­ease pa­tients be will­ing to risk a 12-hour sham brain surgery if it means a gene ther­a­py for their fa­tal con­di­tion might ul­ti­mate­ly be ap­proved?

That’s the im­plied ques­tion at the heart of uniQure’s dis­pute with the FDA, as an in­creas­ing num­ber of rare dis­ease com­pa­nies have come un­der height­ened — and of­ten con­tra­dic­to­ry — reg­u­la­to­ry scruti­ny. Un­der FDA Com­mis­sion­er Mar­ty Makary, the agency has trum­pet­ed ef­forts to ac­cel­er­ate rare dis­ease drug ap­provals, while at the same time re­ject­ing such treat­ments and in­sist­ing that they be test­ed in clin­i­cal tri­als that may not be fea­si­ble.

Bar­clay But­ler, deputy com­mis­sion­er for op­er­a­tions and chief op­er­at­ing of­fi­cer in the FDA's of­fice of op­er­a­tions, will re­tire in the com­ing months, ac­cord­ing to an email to staff from FDA Com­mis­sion­er Mar­ty Makary that was re­viewed by End­points News.

But­ler's deputy, Melanie Keller, will take over both of his roles on April 6, ac­cord­ing to Makary's email. She has spent the last two decades at the NIH and FDA.

An FDA spokesper­son con­firmed the change. Ac­cord­ing to the FDA's web­site, But­ler over­sees "man­age­ment of busi­ness pro­grams and op­er­a­tions across the FDA en­ter­prise lev­el, in­clud­ing hu­man re­sources and fa­cil­i­ties."

But­ler took the dual op­er­at­ing roles last March af­ter serv­ing for a decade in the De­fense Health Agency and in the De­part­ment of De­fense.

The FDA has been us­ing an out­side in­ves­ti­ga­tor in a probe of work­place com­plaints against CBER Di­rec­tor Vinay Prasad, a source fa­mil­iar with the mat­ter told End­points News.

Among com­plaints made against Prasad are that he cre­at­ed a tox­ic work­place, ver­bal­ly be­rat­ed staff and re­tal­i­at­ed against staff push­back, three FDA of­fi­cials fa­mil­iar with the ac­cu­sa­tions told End­points. One source de­scribed the FDA in­quiry in­to Prasad as sprawl­ing and go­ing on for months.

The out­side firm, called Pro­fes­sion­al EEO Ser­vices, has been as­sist­ing with the FDA’s probe, ac­cord­ing to the first source, who spoke to End­points on con­di­tion of anonymi­ty. The source said that Prasad was ex­pect­ed to meet with the in­ves­ti­ga­tor this week, though trav­el is­sues dur­ing an East Coast bliz­zard may have de­layed that, the source added.

Rare dis­ease ad­vo­cates and sen­a­tors said they want to see more con­sis­ten­cy in the FDA’s ap­proval process dur­ing an Ag­ing Com­mit­tee hear­ing Thurs­day that ex­am­ined how the agency’s reg­u­la­to­ry process­es have led to de­lays for some ther­a­pies.

Law­mak­ers on both sides of the aisle dis­cussed their frus­tra­tions with the FDA, in­clud­ing the agen­cy's in­abil­i­ty to hire new staff and a re­cent slate of re­jec­tions of rare dis­ease treat­ments. 

“These pa­tients de­pend on a reg­u­la­to­ry process that’s sci­ence-dri­ven and ca­pa­ble of turn­ing re­search in­to re­al treat­ment,” Sen. An­gela Al­so­brooks (D-MD) said. “This ad­min­is­tra­tion is con­stant­ly dis­rupt­ing clin­i­cal tri­als, slow­ing in­no­va­tion and un­der­min­ing the pipeline to cures.”

The FDA has just out­lined which ap­pli­ca­tions might be new­ly el­i­gi­ble for three years of ex­clu­siv­i­ty, in­clud­ing ones where a drug may have been ap­proved in a pre­vi­ous form.

Build­ing off de­f­i­n­i­tions from a 1994 rule, the 14-page draft guid­ance spells out what types of fol­low-on phar­ma ap­pli­ca­tions and clin­i­cal ac­tiv­i­ty would al­low a com­pa­ny to win the three years of clin­i­cal in­ves­ti­ga­tion ex­clu­siv­i­ty — not to be con­fused with the five years of pro­tec­tion for new chem­i­cal en­ti­ties or the sev­en-year ex­clu­siv­i­ty for or­phan drugs treat­ing dis­eases that af­fect few­er than 200,000 peo­ple.

The new dis­tinc­tions are meant to help sup­port de­vel­op­ment of pre­vi­ous­ly ap­proved drugs, ac­cord­ing to the law firm May­er Brown, as well as to pro­tect more new in­di­ca­tions, dosage forms, strengths and dos­ing reg­i­mens.