FDA out­lines a laun­dry list of sur­ro­gate end­points with an eye to ex­pand­ing the ros­ter for drug de­vel­op­ers

The FDA on Wednes­day pub­lished a list of sur­ro­gate end­points to help in­form drug de­vel­op­er dis­cus­sions with rel­e­vant Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) or Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) re­view di­vi­sions.

The list, which was cre­at­ed thanks to the 21st Cen­tu­ry Cures Act, in­cludes sur­ro­gate end­points that spon­sors have used as pri­ma­ry ef­fi­ca­cy clin­i­cal tri­al end­points for ap­proval of new drug ap­pli­ca­tions (NDAs) or bi­o­log­ics li­cense ap­pli­ca­tions (BLAs). It al­so in­cludes sur­ro­gate end­points that may be ap­pro­pri­ate for use as pri­ma­ry ef­fi­ca­cy clin­i­cal tri­al end­points for drug or bi­o­log­ic ap­provals, al­though they have not yet been used to sup­port an ap­proved NDA or BLA.

The list, which will be up­dat­ed every six months, fea­tures sur­ro­gate end­points for nu­mer­ous dis­eases in­clud­ing acromegaly, dif­fer­ent can­cers, chron­ic kid­ney dis­ease, cys­tic fi­bro­sis, he­pati­tis A, B and C, HIV, hy­per­ten­sion and os­teo­poro­sis, among oth­ers.

“The ac­cept­abil­i­ty of these sur­ro­gate end­points for use in a par­tic­u­lar drug or bi­o­log­ic de­vel­op­ment pro­gram will be de­ter­mined on a case-by-case ba­sis,” the FDA said.

The list, which sep­a­rates adult and pe­di­atric end­points, does not in­clude com­pos­ite end­points that are a com­bi­na­tion of bio­mark­er sur­ro­gate end­points and clin­i­cal end­points. The ta­ble al­so does not in­clude sur­ro­gate end­points that may have been ac­cept­ed for past drug de­vel­op­ment pro­grams but are no longer ac­cept­able as an end­point to sup­port reg­is­tra­tion.

And crit­ics of the list note a lack of speci­fici­ty.

Vinay Prasad

Vinay Prasad, as­so­ciate pro­fes­sor of med­i­cine at Ore­gon Health and Sci­ence Uni­ver­si­ty, told Fo­cus: “I would say, at least for can­cer, it is done at such a high lev­el with so lit­tle de­tail, it is pret­ty much use­less. A bet­ter sum­ma­ry of sur­ro­gates used to jus­ti­fy ap­provals and their strength can be found in our pa­per from the Mayo clin­ic pro­ceed­ings…We are show­ing the sur­ro­gate used by ap­proval, the path­way of ap­proval, and the strength of the sur­ro­gate in the bio­med­ical lit­er­a­ture. They just say what sur­ro­gates are used in what tu­mors, but do not ex­plain the line of ther­a­py, the drugs that uti­lized the path­way or the strength of cor­re­la­tion.”

Back­ground

Ac­cord­ing to sec­tion 507(e)(9) of the Food Drug & Cos­met­ic Act, “[t]he term ‘sur­ro­gate end­point’ means a mark­er, such as a lab­o­ra­to­ry mea­sure­ment, ra­di­ograph­ic im­age, phys­i­cal sign, or oth­er mea­sure, that is not it­self a di­rect mea­sure­ment of clin­i­cal ben­e­fit, and (A) is known to pre­dict clin­i­cal ben­e­fit and could be used to sup­port tra­di­tion­al ap­proval of a drug or bi­o­log­i­cal prod­uct; or (B) is rea­son­ably like­ly to pre­dict clin­i­cal ben­e­fit and could be used to sup­port the ac­cel­er­at­ed ap­proval of a drug or bi­o­log­i­cal prod­uct in ac­cor­dance with sec­tion 506(c).”


First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion. 

Author

Zachary Brennan

managing editor, RAPS

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Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

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