The FDA is spelling out the de­tails of a new path­way to help speed per­son­al­ized cell and gene ther­a­pies to mar­ket for rare dis­eases.

Mon­day's long-await­ed draft guid­ance out­lines the agency’s “plau­si­ble mech­a­nism” frame­work, a path­way FDA Com­mis­sion­er Mar­ty Makary and vac­cines chief Vinay Prasad un­veiled last fall for drug de­vel­op­ers pur­su­ing be­spoke ther­a­pies.

The guid­ance de­tails a path to mar­ket for ther­a­pies where a ran­dom­ized tri­al is not fea­si­ble and where there's a spe­cif­ic ge­net­ic, cel­lu­lar or mol­e­c­u­lar ab­nor­mal­i­ty that can be al­tered or cor­rect­ed. Genome edit­ing and RNA-based ther­a­pies, in­clud­ing an­ti­sense oligonu­cleotides, are the fo­cus of the 22-page draft. But the agency notes that the gen­er­al con­cepts may ap­ply to oth­er types of in­di­vid­u­al­ized ther­a­pies.

Top FDA of­fi­cials said that a sin­gle piv­otal tri­al re­quire­ment will be the “new de­fault stan­dard” for drug ap­provals, a move that goes be­yond the agency’s pri­or dis­cre­tion around not re­quir­ing two tri­als.

In a "Sound­ing Board" pub­lished Wednes­day evening in the New Eng­land Jour­nal of Med­i­cine, FDA Com­mis­sion­er Mar­ty Makary and vac­cines chief Vinay Prasad ex­plain that two tri­als can re­duce false-pos­i­tive con­clu­sions. But, they write, "as drug dis­cov­ery be­comes in­creas­ing­ly pre­cise and sci­en­tif­ic," an "over­re­liance on two tri­als no longer makes sense."

The NE­JM piece con­tin­ues Makary's push to make the drug de­vel­op­ment process more seam­less and eas­i­er for in­dus­try. But the shift to one tri­al runs in di­rect con­trast to Prasad's aca­d­e­m­ic ca­reer where he has ar­gued that new on­col­o­gy drugs should be re­quired to demon­strate im­proved over­all sur­vival or qual­i­ty of life rather than just an ef­fect on a sur­ro­gate end­point, which is nec­es­sary for an ac­cel­er­at­ed ap­proval.

Sen. Bill Cas­sidy (R-LA), chair­man of the Sen­ate HELP com­mit­tee, un­veiled new pro­pos­als on how the FDA can im­prove the drug ap­proval process, US com­pet­i­tive­ness with Chi­na, use of re­al-world da­ta and clin­i­cal holds for cell and gene ther­a­pies.

Tues­day's re­port comes as Cas­sidy and Rep. Jake Auch­in­closs (D-MA) have called on FDA Com­mis­sion­er Mar­ty Makary to tes­ti­fy be­fore Con­gress on the agen­cy's safe­ty and ef­fi­ca­cy stan­dards, par­tic­u­lar­ly af­ter vac­cine chief Vinay Prasad over­ruled staff on Mod­er­na's flu vac­cine re­view, which was re­versed on Wednes­day.

"FDA should con­sid­er how to im­prove pre­dictabil­i­ty in the drug re­view process, which should in­clude more ju­di­cious use of clin­i­cal holds and greater trans­paren­cy in its di­a­logue with spon­sors," Cas­sidy's re­port says. "To ac­cel­er­ate rare dis­ease drug de­vel­op­ment, FDA should more con­sis­tent­ly use tools like ac­cel­er­at­ed ap­proval."

Phar­ma trade groups are lay­ing the foun­da­tion for po­ten­tial le­gal chal­lenges to two CMS pric­ing demon­stra­tions that they say are much broad­er than legal­ly al­lowed and aren't ac­tu­al­ly in­tend­ed to save pa­tients mon­ey.

The re­bukes were out­lined in pub­lic com­ments from the trade groups BIO and PhRMA on two yet-to-be-fi­nal­ized demos re­leased by the Cen­ter for Medicare and Med­ic­aid In­no­va­tion that aim to low­er drug prices for Medicare Part B and Part D, re­spec­tive­ly. The de­mo ad­dress­ing Part B is called GLOBE and the Part D de­mo is called GUARD.

HHS Sec­re­tary Robert F. Kennedy Jr. faces a sec­ond le­gal chal­lenge re­lat­ed to the over­haul of the child­hood vac­cine sched­ule.

Fif­teen states claimed that HHS’ de­ci­sion to down­grade rec­om­men­da­tions for six vac­cines is the “cul­mi­na­tion of a se­ries of un­law­ful ac­tions in fur­ther­ance of Sec­re­tary Kennedy’s idio­syn­crat­ic and un­sci­en­tif­ic hos­til­i­ty to vac­cines,” ac­cord­ing to a law­suit filed Tues­day.

The com­plaint, brought in a fed­er­al court in Cal­i­for­nia, fol­lows a sim­i­lar law­suit filed in Mass­a­chu­setts by lead­ing clin­i­cian groups. That court is ex­pect­ed any day to de­cide whether to pre­lim­i­nar­i­ly block the vac­cine changes.

“This is a pub­lic­i­ty stunt dressed up as a law­suit,” an HHS spokesper­son said in an emailed state­ment. “By law, the health sec­re­tary has clear au­thor­i­ty to make de­ter­mi­na­tions on the CDC im­mu­niza­tion sched­ule.”