Re­al world da­ta and FDA: Drug­mak­ers seek more clar­i­ty on reg­istry guid­ance

As the FDA crafts a new se­ries of guid­ance doc­u­ments on how bio­phar­ma com­pa­nies can use re­al-world da­ta, in­clud­ing pa­tient reg­istries, to help sup­ple­ment their ap­pli­ca­tions, phar­ma com­pa­nies and in­dus­try group PhRMA are call­ing for more de­tails and more con­sis­ten­cy from the agency.

The push from in­dus­try around the use of re­al-world da­ta has been sup­port­ed by both the 21st Cen­tu­ry Cures Act and in­dus­try-ne­go­ti­at­ed PDU­FA VI (the next it­er­a­tion of which is com­ing soon).

In­dus­try group PhRMA ex­plained in a com­ment post­ed last week that com­mon el­e­ments from these co­or­di­nat­ed RWD guid­ance doc­u­ments from FDA “are not al­ways aligned with the rec­om­men­da­tions in this [reg­istry] guid­ance, which may cause con­fu­sion. Sim­i­lar ap­proach­es should be ap­plic­a­ble across many RWD sources and the guid­ances should be aligned ac­cord­ing­ly.”

Re­leased in No­vem­ber, the draft guid­ance is in­tend­ed to help spon­sors and FDA with con­sid­er­a­tions when ei­ther propos­ing to de­sign a reg­istry or us­ing an ex­ist­ing reg­istry to sup­port reg­u­la­to­ry de­ci­sion-mak­ing about a drug’s ef­fec­tive­ness or safe­ty.

“In gen­er­al, reg­istries are bet­ter suit­ed as a da­ta source for reg­u­la­to­ry pur­pos­es when spon­sors aim to cap­ture ob­jec­tive end­points,” the FDA says in the draft, “such as death or hos­pi­tal­iza­tion. Sub­jec­tive end­points, such as pain, can be col­lect­ed in a reg­istry, but ad­di­tion­al chal­lenges are in­volved to stan­dard­ize such mea­sure­ments.”

In­com­ing FDA chief Rob Califf has been a fan of RWD, par­tic­u­lar­ly when ran­dom­ized, and has worked on the top­ic in his pre­vi­ous role at Google’s par­ent com­pa­ny Al­pha­bet. Life sci­ence com­pa­nies, which pre­vi­ous­ly sought more de­tails on pri­or guid­ance docs, are again call­ing on the FDA to ex­plain it­self more.

Na­jat Khan

McKesson, which op­er­ates an on­col­o­gy re­al-world da­ta and ev­i­dence busi­ness called On­ta­da, wrote, “At a min­i­mum, FDA guid­ance should in­clude con­tent around the com­mon types of reg­istries (i.e., pa­tient, spe­cial­ty, provider, de­vice, and pop­u­la­tion-lev­el), and specif­i­cal­ly, their unique char­ac­ter­is­tics should in­clude spe­cif­ic da­ta el­e­ments that make a reg­istry ‘fit-for pur­pose’ for a par­tic­u­lar sci­en­tif­ic ob­jec­tive or use case.”

J&J’s Janssen al­so wants the FDA to go fur­ther in ex­plain­ing how reg­istries might fac­tor in­to the agency’s ben­e­fit-risk as­sess­ments for new drugs:

For ex­am­ple, safe­ty and ef­fi­ca­cy end­points de­rived from reg­istry da­ta can be de­signed with the same breadth and de­tail as those used in the con­text of a ran­dom­ized con­trolled clin­i­cal tri­al. Reg­istry end­points have the ad­van­tage over some oth­er types of da­ta sources as du­pli­ca­tions are more eas­i­ly iden­ti­fied and ad­dressed, and the study time­frames and units cap­tured can be uni­form. Reg­istries al­so have the po­ten­tial to mea­sure sever­i­ty of dis­ease, not just dis­ease oc­cur­rence and can al­low the eval­u­a­tion of ben­e­fits and risks in the re­al-world set­ting. To this end, Janssen re­quests that as the Draft Guid­ance is fi­nal­ized, FDA in­clude dis­cus­sion on how reg­istry da­ta may in­form the ben­e­fit-risk as­sess­ment.

Janssen’s chief da­ta sci­ence of­fi­cer Na­jat Khan wrote that the draft guid­ance “would be sig­nif­i­cant­ly strength­ened if the FDA in­clud­ed dis­cus­sion of chal­lenges and po­ten­tial so­lu­tions as well as ad­van­tages and lim­i­ta­tions of sec­ondary use of reg­istry da­ta.”

Mark Taisey

Am­gen’s VP Bri­an Brad­bury and SVP Mark Taisey called on the FDA to in­clude a few ex­am­ples of reg­istries used for reg­u­la­to­ry de­ci­sion-mak­ing, in­clud­ing the use of an ex­ist­ing reg­istry and the de­sign of a new reg­istry.

They al­so of­fer its own ex­am­ple of the Nordic Coun­try Pa­tient Reg­istry for Romi­plostim, which was orig­i­nal­ly es­tab­lished in 2009 as a post-au­tho­riza­tion safe­ty study to as­sess the long-term safe­ty and out­comes in adult pa­tients with chron­ic im­mune throm­bo­cy­tope­nia and was used to con­duct a study of com­par­a­tive ef­fec­tive­ness of romi­plostim ver­sus SOC with the goal of sup­port­ing an ex­pan­sion of the romi­plostim la­bel.

Bri­an Brad­bury

“Ad­di­tion­al­ly, the EX­PECT preg­nan­cy reg­istry ex­am­ined the oc­cur­rence of ma­jor con­gen­i­tal anom­alies in preg­nant women with se­vere asth­ma treat­ed with oma­l­izum­ab,” Brad­bury and Taisey wrote.

Boehringer In­gel­heim sim­i­lar­ly calls for ex­am­ples of use of re­al-world ev­i­dence, “specif­i­cal­ly reg­istries to sup­port the ap­proval of a new in­di­ca­tion.” Boehringer of­fers the ex­am­ple of use of reg­istry da­ta from the US Sci­en­tif­ic Reg­istry of Trans­plant Re­cip­i­ents for an ap­proval of a new in­di­ca­tion of tacrolimus.

Am­gen al­so calls on the FDA to ex­pand its de­f­i­n­i­tion of RWE in this guid­ance and oth­ers, to in­clude (ad­di­tion in bold), “RWE is the clin­i­cal ev­i­dence about the us­age and the po­ten­tial ben­e­fits or risks of a med­ical prod­uct or about a dis­ease state de­rived from analy­sis of RWD.”

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Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

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Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

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The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

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Paul Hudson, Sanofi CEO (via Getty)

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Janet Woodcock (Sipa via AP Images)

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Adrian Gottschalk, Foghorn Therapeutics CEO

Flag­ship's Foghorn, part­nered with Mer­ck and Eli Lil­ly, gets a par­tial FDA hold af­ter pa­tient death

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