PDU­FA VII: FDA and in­dus­try set pri­or­i­ties in first round of ne­go­ti­a­tions

Af­ter kick­ing off the PDU­FA reau­tho­riza­tion process in Ju­ly, the FDA has re­leased the first set of meet­ing sum­maries in its on­go­ing ne­go­ti­a­tions with in­dus­try that will shape its pre­scrip­tion drug re­view pro­gram from FY2023-2027.

The meet­ing sum­maries, while brief, pro­vide in­sights in­to what FDA and in­dus­try hope to get out of the mul­ti-bil­lion-dol­lar agree­ment, with rep­re­sen­ta­tives from gov­ern­ment and in­dus­try alike agree­ing that the ex­plod­ing field of ad­vanced bi­o­log­ic ther­a­pies must be a pri­or­i­ty. In some oth­er ar­eas, though, the wish lists di­verged.

Steer­ing com­mit­tee

The PDU­FA reau­tho­riza­tion steer­ing com­mit­tee met three times in Sep­tem­ber to hash out the ground rules for the ne­go­ti­a­tions and re­view the ma­jor top­ics and pro­pos­als both sides will work through via des­ig­nat­ed work­ing groups.

FDA and in­dus­try both not­ed the im­pact of the Covid-19 pan­dem­ic on the agency and the reau­tho­riza­tion process at the first meet­ing on Sept. 15.

“De­spite his­toric work­load and op­er­at­ing chal­lenges in the time pe­ri­od, the steps tak­en in PDU­FA VI to pro­tect the pro­gram from fi­nan­cial un­cer­tain­ty have proven crit­i­cal and im­por­tant to main­tain­ing FDA’s op­er­a­tions,” FDA said.

Dur­ing the meet­ing, FDA pitched six ar­eas it wants to fo­cus on for PDU­FA VII: dig­i­tal health and in­for­mat­ics, post­mar­ket, CBER-spe­cif­ic en­hance­ments, pre-mar­ket, reg­u­la­to­ry de­ci­sion tools and fi­nance.

In­dus­try, on the oth­er hand, ex­pressed in­ter­est in “build[ing] up­on past user fee agree­ments and to en­sure FDA and in­dus­try can mu­tu­al­ly keep pace with sci­en­tif­ic de­vel­op­ment.” Top­ics pre­sent­ed by in­dus­try in­clude: “strength­en­ing sci­en­tif­ic di­a­logue, en­hanc­ing pa­tient-cen­tric drug re­view, sup­port­ing the next wave of ad­vanced bi­o­log­ic ther­a­pies, mod­ern­iz­ing reg­u­la­to­ry ev­i­dence gen­er­a­tion, ad­vanc­ing dig­i­tal and IT tech­nolo­gies, en­hanc­ing in­no­va­tion in qual­i­ty and man­u­fac­tur­ing, and op­ti­miz­ing FDA in­fra­struc­ture, staffing, and re­sources.”

In­dus­try al­so said it was keen on adopt­ing some of the lessons from the Covid-19 pan­dem­ic and trans­lat­ing them in­to im­proved process­es go­ing for­ward.

Dur­ing the next steer­ing com­mit­tee meet­ing on Sept. 22, FDA and in­dus­try re­viewed the over­all time­line for reau­tho­riza­tion and the two sides sought clar­i­fi­ca­tion on each oth­er’s pro­posed top­ics. The fol­low­ing week the com­mit­tee met again and re­viewed the time­line for com­mu­ni­cat­ing with Con­gress, agreed to top­ic as­sign­ments and looked at some of the over­lap be­tween the agency’s Covid-19 re­sponse and PDU­FA in­ter­ests.

CBER sub­group

In­creased sup­port for FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) is set to be a fo­cus for both FDA and in­dus­try in the ne­go­ti­a­tions.

FDA told in­dus­try at the first CBER break­out meet­ing that it would like to see en­hanced re­sources for its cell and gene ther­a­py pro­gram, which has been over­whelmed by an in­flux of ap­pli­ca­tions and meet­ing re­quests in re­cent years.

FDA not­ed that its new re­gen­er­a­tive med­i­cine ad­vanced ther­a­py (RMAT) des­ig­na­tion pro­gram has seen ex­po­nen­tial growth and is now out­pac­ing break­through ther­a­py des­ig­na­tions in the Of­fice of Tis­sues and Ad­vanced Ther­a­pies (OTAT), de­spite not re­ceiv­ing any ded­i­cat­ed re­sources for the fledg­ling pro­gram.

With more re­sources, FDA told in­dus­try that it could spend more time on cell and gene ther­a­py sub­mis­sions, pro­vide more op­por­tu­ni­ties for en­gage­ment and de­vel­op pol­i­cy and guid­ance for spon­sors. FDA al­so said it will seek ded­i­cat­ed re­sources for the RMAT pro­gram un­der PDU­FA VII.

In­dus­try sug­gest­ed three CBER-re­lat­ed com­mit­ments it would like to work in­to the reau­tho­riza­tion agree­ment, in­clud­ing work­shops and guid­ance on the use of spon­sor-spe­cif­ic pri­or knowl­edge in gene ther­a­py sub­mis­sions, ev­i­den­tiary stan­dards for RMAT des­ig­na­tion and gene ther­a­py man­u­fac­tur­ing is­sues.

“In­dus­try would like a pub­lic work­shop to fo­cus on key learn­ings from the RMAT pro­gram re­sult­ing in an up­date to the RMAT guid­ance, in­clud­ing po­ten­tial us­es of Re­al World Ev­i­dence (RWE) for reg­u­la­to­ry de­ci­sion mak­ing,” FDA writes, not­ing that mean­ing­ful guid­ance on the mat­ter may be dif­fi­cult to de­vel­op due to the lim­it­ed num­ber of ap­proved cell and gene ther­a­py prod­ucts and the fact that there have not been any prod­ucts ap­proved to date with RMAT des­ig­na­tion.

For gene ther­a­py man­u­fac­tur­ing, in­dus­try specif­i­cal­ly said it would like to ex­plore whether sub­mit­ting por­tions of a CMC mod­ule could fa­cil­i­tate BLA re­view. FDA said it has con­cerns that a par­tial sub­mis­sion could ac­tu­al­ly slow ap­proval down if de­vel­op­ment is on­go­ing but agreed to car­ry the dis­cus­sion for­ward.

Reg­u­la­to­ry de­ci­sion tools

On Sept. 29, the reg­u­la­to­ry de­ci­sion tools sub­group met for the first time, with FDA and in­dus­try re­view­ing po­ten­tial ar­eas of en­hance­ment and agree­ing to a sched­ule for the next sev­er­al meet­ings.

FDA raised four top­ics it would like to tack­le in PDU­FA VII, in­clud­ing mod­el-in­formed drug de­vel­op­ment (MIDD), com­plex in­no­v­a­tive tri­al de­signs (CID), pa­tient-fo­cused drug de­vel­op­ment (PFDD), and ad­vanc­ing trans­la­tion­al mod­els and tools for drug de­vel­op­ment (ATMT).

For MIDD, FDA said its goal is to build on the lessons learned dur­ing PDU­FA VI and to en­sure the pro­gram’s sus­tain­abil­i­ty. Do­ing so would re­quire pub­lic en­gage­ment and the de­vel­op­ment of “com­pre­hen­sive end-to-end guid­ance,” which FDA said would ne­ces­si­tate in­creased staffing.

Dig­i­tal health and in­for­mat­ics

FDA and in­dus­try be­gan dis­cus­sions aimed at en­hanc­ing the use of dig­i­tal health and in­for­mat­ics tech­nolo­gies un­der PDU­FA VII on Sept. 30.

FDA pitched three top­ics for dis­cus­sion at the meet­ing, in­clud­ing a pro­pos­al for an in­te­grat­ed cloud-based tech­nol­o­gy en­vi­ron­ment, a frame­work for lever­ag­ing dig­i­tal health tech­nol­o­gy-gen­er­at­ed da­ta in sub­mis­sions, and CBER IT mod­ern­iza­tion.


FDA and in­dus­try ad­dressed sev­er­al pre­mar­ket is­sues in the first meet­ing of the pre­mar­ket sub­group, in­clud­ing user re­lat­ed risk analy­sis (UR­RA) and hu­man fac­tor (HF) pro­to­col re­view and de­vel­op­ing ef­fi­ca­cy end­points for rare dis­eases.

FDA pro­posed in­creas­ing the user fee time­line for re­view­ing HF pro­to­cols and said the cur­rent goals will be un­sus­tain­able in the fu­ture due to in­creas­ing vol­ume and com­plex­i­ty of HF sub­mis­sions. The two sides dis­cussed the cre­ation of a new user fee goal and time­line for re­view of UR­RA.


At the first of two fi­nance sub­group meet­ings, FDA pre­sent­ed a host of goals for PDU­FA VII: “To en­hance the op­er­a­tional ca­pa­bil­i­ties, ef­fi­ca­cy, and agili­ty of the PDU­FA pro­gram. FDA pro­posed con­tin­u­ing to ad­vance re­source ca­pac­i­ty plan­ning, up­dat­ing the in­fla­tion ad­just­ment to ac­cu­rate­ly ac­count for pro­gram costs, en­hanc­ing flex­i­bil­i­ty in the op­er­at­ing re­serve, elim­i­nat­ing a prob­lem­at­ic lim­i­ta­tion on al­low­able ex­pen­di­tures, stream­lin­ing an­nu­al re­port­ing re­quire­ments, and im­ple­ment­ing tech­ni­cal fix­es.”

In­dus­try rep­re­sen­ta­tives, how­ev­er, stressed that their goal is to build on the en­hance­ments made in PDU­FA VI and to im­prove on user fee re­source man­age­ment, hir­ing and re­ten­tion of re­view staff and per­for­mance re­port­ing.

Dur­ing the sec­ond fi­nance meet­ing, FDA and in­dus­try looked at a pro­pos­al to clar­i­fy the max­i­mum and min­i­mum amount of op­er­at­ing re­serves to be main­tained each year and a pro­pos­al to fur­ther im­ple­ment the re­source ca­pac­i­ty plan­ning (RCP) ca­pa­bil­i­ty in­sti­tut­ed in PDU­FA VI.

Stake­hold­er meet­ing

FDA al­so re­leased a meet­ing sum­ma­ry from the first round of stake­hold­er dis­cus­sions. More than 60 stake­hold­er or­ga­ni­za­tions, in­clud­ing pa­tient groups, con­sumer rep­re­sen­ta­tives, pub­lic health ad­vo­cates and med­ical as­so­ci­a­tions, reg­is­tered to at­tend the meet­ing, though a third of those reg­is­tered did not at­tend.

“Some of the themes fre­quent­ly cit­ed by stake­hold­ers in­clud­ed en­hanc­ing the in­cor­po­ra­tion of pa­tient voice in drug de­vel­op­ment and reg­u­la­to­ry de­ci­sion mak­ing, mod­ern­iz­ing FDA’s in­fra­struc­ture, en­sur­ing FDA has ad­e­quate re­sources to re­cruit and re­tain qual­i­fied staff in­clud­ing in the ar­eas of cell and gene ther­a­py, in­creas­ing the strength and reach of pa­tient and rare dis­ease pro­grams in­clud­ing im­prov­ing  di­ver­si­ty in clin­i­cal tri­als and pa­tient en­gage­ment, en­hanc­ing FDA’s use of reg­u­la­to­ry sci­ence (e.g. COAs, MIDD, RWE), and im­prov­ing the in­te­gra­tion of and guid­ance for the use of re­al-world ev­i­dence (RWE),” FDA re­port­ed. Stake­hold­ers al­so raised de­cen­tral­ized tri­als and lessons learned dur­ing the Covid-19 pan­dem­ic as top­ics for fu­ture dis­cus­sions.

FDA tasked stake­hold­ers with iden­ti­fy­ing their top is­sues for fur­ther dis­cus­sion and said it would sur­vey them to rank the top­ics on the agreed-to short­list.

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Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; 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.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Bo Cumbo, new Solid Bio CEO

Sol­id Bio gets a new CEO, $75M cash and drops lead drug as big in­vestors ju­ry-rig a merg­er deal

Three months after Endpoints News broke the story that gene therapy outfit AavantiBio had gutted its CMC group in a reorganization, the biotech’s CEO has helped engineer a merger with struggling penny stock player Solid Bio. And he’s going to remain in charge of the combined operation, as Solid founder Ilan Ganot steps aside.

The merger news this morning features some high-profile investors.

Perceptive Advisors, RA Capital Management and Bain Capital Life Sciences are leading a $75 million raise to add to the pool of cash Solid will have after the tie-up. That will leave Solid $215 million in cash as Bain’s Adam Koppel jumps on the board — enough to pay for ops and get through some key data milestones on their way into 2025.

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