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Endpoints News – Cancer research groups urge FDA to overhaul standards for early cell therapy trials, cutting time and cost. But will “pre-competitive” alliances fly?

Endpoints News – Cancer research groups urge FDA to overhaul standards for early cell therapy trials, cutting time and cost. But will “pre-competitive” alliances fly?

Two in­flu­en­tial non­prof­its fo­cused on can­cer drug R&D are urg­ing the FDA to take a more flex­i­ble ap­proach to clin­i­cal work to help triage an in­flux of new cell and gene can­cer ther­a­pies mak­ing their way to hu­man stud­ies. By chang­ing cur­rent IND and man­u­fac­tur­ing stan­dards, they say, the agency can cut the time and cost of early-​stage work, ac­cel­er­at­ing the ad­vance of the most promis­ing ther­a­pies in the pipeline. 


But can they get the in­dus­try to agree on data shar­ing and pre-​competitive al­liances?


The Parker In­sti­tute for Can­cer Im­munother­apy and the Friends of Can­cer Re­search pro­duced a white pa­per to per­suade the FDA to adopt new ex­ploratory IND guide­lines that would al­low de­vel­op­ers to quickly steer their cell ther­apy can­di­dates into tiny hu­man stud­ies, al­low­ing re­searchers to quickly try out ther­a­peu­tic doses on dy­ing pa­tients who have run out of treat­ment op­tions.


Eval­u­at­ing the be­hav­ior of cel­lu­lar prod­ucts in hu­mans is cur­rently the most ef­fec­tive way to as­sess safety, since an­i­mal mod­els have been un­re­li­able and prod­uct qual­ity at­trib­utes that pre­dict safety have been dif­fi­cult to iden­tify.


The groups brought to­gether a va­ri­ety of can­cer drug R&D play­ers to­gether on Fri­day to dis­cuss the move, in­clud­ing Axel Hoos from GSK and other rep­re­sen­ta­tives from No­var­tis, Cel­gene, Al­lo­gene and more.


To do it right, the ad­vo­cates say, re­searchers could divvy up pa­tients into small co­horts who would be given a ther­apy on a dose es­ca­la­tion ba­sis. A safety mon­i­tor­ing com­mit­tee could be cre­ated to watch out for dan­ger signs and the data could be mon­i­tored for safety, ef­fi­cacy as well as fu­til­ity.


The groups also want to re­lax man­u­fac­tur­ing stan­dards for very early test­ing, drop­ping some of the re­quire­ments now in place and re­serv­ing them for later stages of de­vel­op­ment, if the can­di­date ther­apy goes on to the next stage of de­vel­op­ment. “Rep­re­sen­ta­tive” vi­ral vec­tors, for ex­am­ple, could be used in gene ther­apy work, speed­ing the clin­i­cal ef­fort with­out ex­pos­ing pa­tients to a sig­nif­i­cant de­gree of added risk.


We note that if re­mark­able ef­fi­cacy were seen for a prod­uct de­vel­op­ment can­di­date tested in an “ex­ploratory IND, the re­quire­ment for a full IND with more stan­dard man­u­fac­tur­ing process de­vel­op­ment would still ap­ply with the po­ten­tial for as­so­ci­ated de­lays.


Why not elim­i­nate FDA re­quire­ments on cGMP grade plas­mids and let the spon­sor han­dle that, by­pass­ing the queues that are form­ing around a few se­lect providers, they ask. Elim­i­nat­ing the need for an E. coli mas­ter cell bank would help cut the time and money needed for one of the first hu­man tri­als. And adopt­ing “parent-​child” INDs, where a main IND could pro­vide the ba­sic con­tent re­quired to ap­prove ad­di­tional INDs around T cell ther­a­pies.


Done prop­erly, they add, the time needed to set up the man­u­fac­tur­ing for one of these early-​stage ther­a­pies could be cut in half.


The biggest chal­lenge, though, could be in ad­vanc­ing their ideas of see­ing the FDA co­or­di­nate with acad­e­mia and in­dus­try on new “pre-​competitive” con­sor­tiums that could work to­gether to test var­i­ous ap­proaches and ther­a­pies aimed at the same tar­get — some­thing in­dus­try has been loathe to adopt.


Col­lab­o­ra­tions that pro­mote and fa­cil­i­tate prospec­tive data col­lec­tion us­ing com­mon data el­e­ments and con­trolled vo­cab­u­lar­ies to en­able cross-​study analy­ses are es­sen­tial to sig­nif­i­cantly ad­vance de­vel­op­ment of cell and gene ther­a­pies in on­col­ogy. Oc­cur­ring well be­fore com­mer­cial­iza­tion, such col­lab­o­ra­tions would pro­vide a proof-​of-concept for gen­er­at­ing stan­dard­ized data to in­form the early stages of in­ves­ti­ga­tional prod­uct de­vel­op­ment. The es­tab­lish­ment of a com­mon study plat­form would fos­ter col­lab­o­ra­tion across mul­ti­ple ap­proaches with con­sis­tent de­sign, stan­dard­ized data col­lec­tion, and analy­sis. 


Taken to­gether these pro­pos­als would fun­da­men­tally al­ter the way much early-​stage can­cer R&D is done. With the phe­nom­e­nal suc­cess of PD-​1 ther­a­pies like Op­divo and Keytruda and the in­tro­duc­tion of the first CAR-​Ts, the R&D world has shifted a mas­sive amount of cap­i­tal into on­col­ogy over the past 5 years. That, in turn, has spurred a big in­crease in the can­cer drug pipeline, while also test­ing the sys­tem’s abil­ity to find all the pa­tients and re­sources needed to prep these drugs for hu­man tri­als.


Whether the in­dus­try can see past the present lim­i­ta­tions and adopt a dif­fer­ent ap­proach of their own while urg­ing the FDA to evolve its stan­dards will test every­one’s re­solve.…