Got­tlieb tack­les spec­u­la­tors, FDA trans­paren­cy and the R&D gold stan­dard in a last round of queries ahead of con­fir­ma­tion vote

Field­ing a fi­nal bar­rage of writ­ten ques­tions from a group of skep­ti­cal De­mo­c­ra­t­ic US Sen­a­tors ahead of to­day’s com­mit­tee vote on Scott Got­tlieb’s nom­i­na­tion as head of the FDA, the na­tion’s like­ly next Com­mis­sion­er of Food and Drugs vowed to square off against fi­nan­cial spec­u­la­tors who are gam­ing the sys­tem to charge high prices, reaf­firmed his un­wa­ver­ing sup­port for the coun­try’s gold stan­dard on drug de­vel­op­ment and re­views and called for pub­lish­ing most of what the agency’s CRLs say about reg­u­la­tors’ rea­sons for re­ject­ing a mar­ket­ing ap­pli­ca­tion.

This in­ter­change be­tween the prospec­tive head of the FDA and law­mak­ers helps il­lus­trate key points Got­tlieb is like­ly to raise in the com­ing years with the world’s drug de­vel­op­ers. And they mark a clear line in the sand that il­lus­trates where the agency is like­ly to be more — and less — ac­com­mo­dat­ing for com­pa­nies charged with han­dling the world’s drug pipeline.

De­mo­c­ra­t­ic Sen­a­tors Robert Casey (D-PA) and Al Franken (D-MI) both pressed him on drug pric­ing and the role he could play at the FDA in bring­ing costs down. Franken in par­tic­u­lar cit­ed hun­dreds of gener­ic drugs with no cur­rent com­pe­ti­tion, leav­ing them wide open to play­ers like Mar­tin Shkre­li, the for­mer CEO at Tur­ing, who hiked the price of gener­ic Dara­prim by more than 5000%, trig­ger­ing a lin­ger­ing con­tro­ver­sy.

Here is Got­tlieb’s an­swer, which he re­peat­ed in oth­er re­spons­es to the ar­ray of ques­tions he faced (em­pha­sis added):

While drug pric­ing does not fall di­rect­ly with­in FDA’s purview, I be­lieve the agency can play an im­por­tant role on this im­por­tant is­sue by tak­ing steps to im­prove prod­uct com­pe­ti­tion. If con­firmed, I will work to en­sure FDA has the ap­pro­pri­ate poli­cies and process­es in place to ef­fec­tive­ly fa­cil­i­tate gener­ic mar­ket en­try and com­pe­ti­tion, es­pe­cial­ly for com­plex drugs that some­times don’t face ef­fec­tive gener­ic com­pe­ti­tion even long af­ter patent ex­piries. Re­form­ing the reg­u­la­to­ry path­way for com­plex gener­ic prod­ucts would ad­dress one key pol­i­cy de­fi­cien­cy that re­sults in un­nec­es­sary bar­ri­ers to the de­vel­op­ment and re­view of gener­ic com­peti­tors for some in­no­va­tor prod­ucts for which tra­di­tion­al bioe­quiv­a­lence and bioavail­abil­i­ty test­ing alone are some­times in­suf­fi­cient for prov­ing same­ness. FDA should al­so ex­plore op­tions to im­prove the ef­fi­cien­cy and con­sis­ten­cy of AN­DA re­view process­es and time­lines, so that fi­nan­cial spec­u­la­tors can­not en­gage in a reg­u­la­to­ry ar­bi­trage, by dra­mat­i­cal­ly hik­ing the price of some very old gener­ic drugs be­cause they know it can take years for new gener­ic com­peti­tors to en­ter the mar­ket.

Sen­a­tor Shel­don White­house (D-RI) not­ed that there have been oc­ca­sions when gener­ic man­u­fac­tur­ers protest­ed that brand­ed drug man­u­fac­tur­ers were rais­ing hur­dles on ac­cess­ing drugs to de­lay cheap knock­offs.

Part of Got­tlieb’s re­sponse:

If man­u­fac­tur­ers in­ap­pro­pri­ate­ly refuse to pro­vide their prod­uct to prospec­tive gener­ic com­peti­tors, this would be a con­cern to FDA and be­come a mat­ter for po­ten­tial en­force­ment ac­tion by the Fed­er­al Trade Com­mis­sion.

Al­so, he added, re­form­ing the path­way on com­plex gener­ics could al­so help ad­dress this.

Tam­my Bald­win (D-WI) en­cour­aged Got­tlieb to get be­hind new rules to use pa­tient-re­port­ed out­comes mea­sures in the re­view process, to “cap­ture da­ta be­yond just dis­ease symp­toms and phys­i­cal func­tion­ing to in­clude psy­choso­cial health mea­sures, in­clud­ing dis­tress screen­ing (e.g., con­cerns re­lat­ed to dis­rup­tion of work/fam­i­ly life [due to the reg­i­men], con­cerns re­lat­ed to nu­tri­tion, fi­nan­cial im­pact and oth­ers). This would pro­vide mean­ing­ful pa­tient feed­back about is­sues that may not be iden­ti­fied through the cur­rent mea­sures be­ing used in the clin­i­cal tri­al process.”


I strong­ly agree that pa­tient ex­pe­ri­ences, pref­er­ences, and per­spec­tives should play an im­por­tant and ap­pro­pri­ate role in FDA’s reg­u­la­to­ry pol­i­cy-mak­ing and de­ci­sion-mak­ing. Among oth­er ap­proach­es, I have ad­vo­cat­ed that we con­tin­ue to ad­vance well-val­i­dat­ed, sci­en­tif­ic tools for in­cor­po­rat­ing Pa­tient Re­port­ed Out­comes (PROs) as end­points in clin­i­cal tri­als. I sup­port these and oth­er mea­sures that would al­low mean­ing­ful pa­tient feed­back to be in­cor­po­rat­ed in­to reg­u­la­to­ry de­ci­sion mak­ing to bet­ter de­fine pa­tient-ex­pe­ri­ence da­ta that may not be iden­ti­fied through the cur­rent mea­sures be­ing used in the clin­i­cal tri­al process.

Sen­a­tor Christo­pher Mur­phy (D-CT) raised Got­tlieb’s stand on trans­paren­cy, an is­sue that comes up rou­tine­ly for an agency barred by law from dis­cussing de­tails on drug da­ta — and much more.

I am a strong pro­po­nent of da­ta trans­paren­cy—for pa­tients, physi­cians, and man­u­fac­tur­ers. I have long ad­vo­cat­ed that the FDA re­lease more in­for­ma­tion re­lat­ed to its own re­view process that could be used to bet­ter in­form con­sumers and prod­uct de­vel­op­ers alike. If con­firmed, I will be com­mit­ted to work­ing with Con­gress, pa­tients, in­dus­try, and stake­hold­ers on the is­sue of da­ta trans­paren­cy and new ways that FDA could po­ten­tial­ly make im­por­tant of its own in­for­ma­tion and de­lib­er­a­tions more read­i­ly avail­able to the pub­lic.

And in an­oth­er an­swer to one of Sen­a­tor Eliz­a­beth War­ren’s (D-MA) ques­tions, he added an im­por­tant point on his com­mit­ment to open­ing up more.

This in­cludes the com­plete re­sponse let­ters, af­ter prop­er redac­tion of com­mer­cial con­fi­den­tial in­for­ma­tion.

Through it all, Got­tlieb re­peat­ed­ly com­mit­ted to main­tain­ing the agency’s stan­dards on prov­ing a drug’s ef­fi­ca­cy and safe­ty ahead of an ap­proval. And he stuck to that as Sen­a­tor Pat­ty Mur­ray (D-WA) ques­tioned where he would draw the line and new drug ap­provals, cit­ing some crit­i­cism from Got­tlieb five years ago.

FDA has made sig­nif­i­cant progress in re­cent years to en­sure that pa­tients in the U.S. have ac­cess to new, in­no­v­a­tive ther­a­pies thanks to new leg­isla­tive path­ways like Break­through Ther­a­py des­ig­na­tion. The adop­tion of the Break­through path­way ad­dressed many of the con­cerns I raised in that 2012 ar­ti­cle. I be­lieve we should con­tin­ue to look for ways to im­prove the ef­fi­cien­cy of FDA’s med­ical prod­uct re­view pro­gram, mod­ern­ize the sci­en­tif­ic stan­dards used in drug reg­u­la­tion, and seek more uni­form adop­tion of path­ways cre­at­ed by Con­gress like the Break­through Des­ig­na­tion, and build on these op­por­tu­ni­ties through adop­tion of the new pro­vi­sions in Con­gress in 21st Cen­tu­ry Cures. We need to do all these things while con­tin­u­ing to en­sure that new prod­ucts meet FDA’s Gold Stan­dard for safe­ty and ef­fi­ca­cy.

In an­oth­er re­sponse, he not­ed:

Main­tain­ing the Gold Stan­dard of safe­ty and ef­fi­ca­cy for med­ical prod­ucts is fun­da­men­tal to FDA’s mis­sion to pro­tect and pro­mote pub­lic health.

Got­tlieb al­so re­peat­ed that his of­ten cit­ed busi­ness ties to com­pa­nies like Glax­o­SmithK­line, which had paid him $60,000 a year plus trav­el ex­pens­es for his ad­vice, Ver­tex, Cel­gene and oth­ers were al­ready or about to be sev­ered, vow­ing to seek coun­sel from ethics ad­vis­ers af­ter re­cus­ing him­self from any de­ci­sions about his for­mer clients and busi­ness in­vest­ments.

Got­tlieb is dig­ging in for the du­ra­tion.

Im­age: Com­mis­sion­er-des­ig­nate Scott Got­tlieb at his nom­i­na­tion hear­ing in ear­ly April Zach Gib­son/Get­ty Im­ages

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; and more

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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.