US pol­i­cy and reg­u­la­to­ry changes im­pact­ing com­mer­cial­iza­tion of cell and gene ther­a­pies

Key take­aways:

• The cell and gene mar­ket still faces a lack of co­he­sion across stake­hold­ers when it comes to clas­si­fi­ca­tion of prod­ucts
• Ex­per­tise is in dis­parate pock­ets across the FDA, mak­ing it chal­leng­ing to plan re­view teams
• Reg­u­la­tors and pol­i­cy­mak­ers are plac­ing greater em­pha­sis on ac­cu­rate and di­verse rep­re­sen­ta­tion in tri­al pop­u­la­tions
• Tai­lor­ing an ef­fec­tive ev­i­dence-gen­er­a­tion plan at the clin­i­cal phase is vi­tal for en­sur­ing on­go­ing ev­i­dence gen­er­a­tion re­mains in­for­ma­tive in­to prod­uct life cy­cle

This is an ex­tract from Fishawack Health’s new pub­li­ca­tion on the cell and gene ther­a­py land­scape. Down­load it here.

The cell and gene mar­ket is evolv­ing at light­ning speed. Since the ap­proval of the first CAR-T ther­a­py in 2017, more than 20 cell and gene ther­a­pies have been ap­proved by the FDA. This in­cludes six CAR-T and four gene ther­a­pies.¹ To­day, the pipeline is filled with hun­dreds of these nov­el can­di­dates, of­ten de­signed to treat ther­a­peu­tic ar­eas with high un­met need and lim­it­ed al­ter­na­tive treat­ments. This has led to a dy­nam­ic land­scape in which the FDA has strug­gled to up­skill in the com­plex sci­ence and the ris­ing de­mand for reg­u­la­to­ry ex­per­tise. As a re­sult, it is now turn­ing to leg­isla­tive and/or reg­u­la­to­ry up­dates to help ex­pe­dite ap­provals.

In turn, bio­phar­ma­ceu­ti­cal com­pa­nies are com­pelled to think crit­i­cal­ly about ev­i­dence gen­er­a­tion to meet the ap­proval and post-ap­proval de­mands of var­i­ous stake­hold­ers, in­clud­ing reg­u­la­tors and pay­ers, as ev­i­dence of nov­el cell and gene ther­a­py ef­fec­tive­ness may be more piv­otal to ap­proval and cov­er­age de­ci­sions, while al­so be­ing hard­er to ob­tain in a tra­di­tion­al clin­i­cal tri­al set­ting.

Man­u­fac­tur­ers will need to em­ploy a ro­bust strat­e­gy and im­ple­ment metic­u­lous plan­ning pro­ce­dures ear­ly in the drug de­vel­op­ment process to ac­count for the evolv­ing reg­u­la­to­ry and pol­i­cy land­scape. This in­cludes an in­creased fo­cus on ar­eas such as health eq­ui­ty, pa­tient-fo­cused drug de­vel­op­ment, and clin­i­cal tri­al di­ver­si­ty.

Avalere Health, which joined Fishawack Health in June 2022, is a lead­ing health­care con­sult­ing firm based in Wash­ing­ton, DC. Avalere’s team of more than 200 ad­vi­sors of­fers vast ex­pe­ri­ence and ex­per­tise in fed­er­al pol­i­cy and pol­i­cy de­vel­op­ments across all 50 states.

Kylie Sten­gel, Pol­i­cy Con­sul­tant, and Mark Von Eisen­burg, Mar­ket Ac­cess Con­sul­tant, shed light on the key FDA reg­u­la­to­ry chal­lenges and the im­pact of US pol­i­cy changes for prod­uct de­vel­op­ers, high­light­ing con­sid­er­a­tions that will equip com­pa­nies to plan ef­fec­tive­ly.

FH: There are a sig­nif­i­cant num­ber of cell and gene ther­a­pies in the pipeline, rais­ing some ques­tions around the FDA’s abil­i­ty to keep up with ap­pli­ca­tion re­views. Can you tell us about some of the FDA reg­u­la­to­ry chal­lenges?

Mark: In the pre­clin­i­cal phase, one of the core is­sues the cell and gene mar­ket still faces is lack of co­he­sion across stake­hold­ers when it comes to clas­si­fi­ca­tion of prod­ucts. We’re op­er­at­ing with emerg­ing biotech­nol­o­gy in which com­bi­na­tions of nov­el tech­nolo­gies and com­plex man­u­fac­tur­ing process­es might be in­ter­min­gled be­tween a gene ther­a­py and a cell ther­a­py or as­pects of both.

An­oth­er chal­lenge is that we don’t want the nov­el­ty of tech­nol­o­gy to force riski­er or in­ef­fi­cient poli­cies or reg­u­la­to­ry process­es. How­ev­er, from what we see now, the tech­nol­o­gy will out­pace some of the reg­u­la­to­ry prece­dents, which aligns with the his­tor­i­cal­ly re­ac­tionary man­ner in which re­view ex­per­tise is gained for nov­el tech­nolo­gies.

Sim­i­lar­ly, in the pre­clin­i­cal phase, you need to think about where the ex­per­tise might lie at the FDA. This is an im­por­tant con­sid­er­a­tion be­cause we think about cell and gene ther­a­pies be­ing reg­u­lat­ed by the Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search. But there are in­stances, for ex­am­ple, with RNA ther­a­peu­tics, where bi­o­log­ics are reg­u­lat­ed by the Cen­ter for Drug Eval­u­a­tion and Re­search, be­cause that’s where the FDA ex­per­tise is, so plan­ning re­view teams is an ad­di­tion­al chal­lenge. We see the FDA work­ing on its cur­rent think­ing re­gard­ing CAR-T–spe­cif­ic cell ther­a­py, as well as gene ther­a­py–spe­cif­ic man­u­fac­tur­ing guid­ance. Al­though these pub­li­ca­tions might pro­vide ar­eas of clar­i­ty for prod­uct spon­sors, there’s still a need for best prac­tices when it comes to this ear­ly stage of de­vel­op­ment.

FH: On the leg­isla­tive front, do we see any move­ment as it in­ter­sects with pre­clin­i­cal or ear­ly-stage reg­u­la­to­ry chal­lenges?

Kylie: The House draft User Fee Amend­ment or UFA reau­tho­riza­tion bill re­leased in May 2022 would have re­quired the FDA to con­vene a pub­lic work­shop on the best prac­tices for gen­er­at­ing sci­en­tif­ic da­ta to fa­cil­i­tate the de­vel­op­ment of hu­man tis­sue and cel­lu­lar-based prod­ucts. Ad­di­tion­al­ly, the draft Cures 2.0 leg­is­la­tion would re­quire the FDA to sub­mit a re­port to Con­gress on the FDA’s chal­lenges re­lat­ed to cell and gene prod­ucts in the next 10 years and what’s need­ed to ad­dress those chal­lenges. This bill is still pro­posed in the US House of Rep­re­sen­ta­tives and has yet to be con­sid­ered. How­ev­er, now that the User Fee pro­gram has been ad­vanced in­to law (on Sep­tem­ber 30) with­out ad­di­tion­al pol­i­cy rid­ers be­ing in­clud­ed, some pro­vi­sions spe­cif­ic to cell and gene ther­a­pies will be­come law be­fore their im­pact is felt.

FH: Now that we’ve dis­cussed the pre­clin­i­cal phase, can you high­light some of the core chal­lenges in the clin­i­cal phase?

Mark: The first that comes to mind has to do with this top­ic of pa­tient-fo­cused drug de­vel­op­ment. This re­lates to a push we’ve seen re­cent­ly—fu­eled by some learn­ings from the COVID-19 pan­dem­ic—for get­ting ac­cu­rate rep­re­sen­ta­tion in your tri­al pop­u­la­tion. The chal­lenge of gen­er­at­ing pow­ered da­ta for a small pa­tient pop­u­la­tion is a key is­sue for many cell and gene ther­a­pies that are un­der de­vel­op­ment. We need to see in­no­v­a­tive meth­ods for con­tin­u­ous mon­i­tor­ing of pa­tients for use of re­al-world da­ta and stan­dard­iz­ing this in­to re­al-world ev­i­dence to as­sist on both the pre- and post-mar­ket sides of ev­i­dence gen­er­a­tion.

Ad­di­tion­al­ly in the clin­i­cal phase, we think about the con­cept of FDA-ex­pe­dit­ed de­vel­op­ment and ap­proval path­ways. There are quite a few of these and they are par­tic­u­lar­ly rel­e­vant to cell and gene ther­a­pies, which of­ten treat dis­eases that have high un­met med­ical needs or are se­ri­ous and life-threat­en­ing.

Tai­lor­ing an ef­fec­tive ev­i­dence-gen­er­a­tion plan at the clin­i­cal phase so that your on­go­ing ev­i­dence gen­er­a­tion re­mains in­for­ma­tive in­to the prod­uct life cy­cle is a chal­lenge that cell and gene ther­a­py man­u­fac­tur­ers might face at a high­er rate than oth­er man­u­fac­tur­ers.

Get the full analy­sis 

This is an ex­tract from Fishawack Health’s new pub­li­ca­tion on the cell and gene ther­a­py land­scape.

Down­load the re­port to ac­cess the full ar­ti­cle pro­vid­ing fur­ther analy­sis of the re­view stage, pa­tient-fo­cused drug de­vel­op­ment, and ex­pe­dit­ed path­ways.

In the pub­li­ca­tion, you will al­so gain in­sights on:

• As­traZeneca’s in­no­va­tion in cell ther­a­py for chron­ic dis­eases
• Gene edit­ing to treat blood dis­or­ders
• Trends shap­ing the fu­ture of per­son­al­ized med­i­cine
• Com­mu­ni­cat­ing com­plex sci­ence to non­ex­pert stake­hold­ers

About the Au­thors

Kylie Sten­gel, Pol­i­cy Con­sul­tant
Kylie is a pol­i­cy con­sul­tant who fo­cus­es on reg­u­la­to­ry and leg­isla­tive de­vel­op­ments, with spe­cif­ic ex­per­tise in Medicare Part D pay­ment and pol­i­cy, drug pric­ing re­forms, and health in­sur­ance mar­kets. She sup­ports clients span­ning a range of health­care sec­tors and stake­hold­ers in as­sess­ing the im­pacts of the evolv­ing pol­i­cy land­scape on their busi­ness and ad­vo­ca­cy pri­or­i­ties.

Mark Von Eisen­burg, Mar­ket Ac­cess Con­sul­tant
As a spe­cial­ist in mar­ket ac­cess, Mark cou­ples his train­ing in age-re­lat­ed dis­eases, specif­i­cal­ly Alzheimer’s dis­ease, with a back­ground in ef­fec­tive sci­en­tif­ic com­mu­ni­ca­tion to help clients un­der­stand trans­la­tion­al re­search and sci­ence pol­i­cy and to de­liv­er di­gestible in­sights that in­form mar­ket ac­cess strate­gies.

About Fishawack Health

Es­tab­lished in 2001, Fishawack Health (FH) is a pur­pose­ful­ly built com­mer­cial­iza­tion part­ner for the bio­phar­ma­ceu­ti­cal, med­ical tech­nol­o­gy, and well­ness in­dus­tries. Our 1,500+ ex­perts com­bine their knowl­edge and ex­per­tise across our core dis­ci­plines—Med­ical; Mar­ket­ing; Pol­i­cy; Val­ue, Ev­i­dence, and Ac­cess; and Con­sult­ing—to cre­ate the con­nec­tions that make bet­ter health hap­pen.

We part­ner with our clients to nav­i­gate the com­plex and rapid­ly chang­ing health­care ecosys­tem. To­geth­er, we re­al­ize the po­ten­tial of strate­gies and so­lu­tions to bring in­no­va­tion to the hands of those who can ben­e­fit from it.