Stephen Hahn, FDA commissioner (AP Images)

PDU­FA VII: FDA, in­dus­try pre­view their reau­tho­riza­tion wish lists

At its first pub­lic meet­ing in the runup to the reau­tho­riza­tion of the Pre­scrip­tion Drug User Fee Actthe FDA, in­dus­try and oth­er stake­hold­ers on Thurs­day shed light on their goals for what will be the agency’s sev­enth PDU­FA pro­gram.

The meet­ing, held ful­ly vir­tu­al­ly for the first time due to the COVID-19 pan­dem­ic, is the start­ing point for the ne­go­ti­a­tions with in­dus­try and dis­cus­sions with stake­hold­ers that will shape FDA’s new drug re­view pro­gram from FY2023-FY2027.

Go­ing from VI to VII

FDA com­mis­sion­er Stephen Hahn opened the meet­ing by tout­ing the suc­cess­es of the cur­rent PDU­FA pro­gram. “Since FY2016, near­ly five years af­ter our pre­vi­ous meet­ing, CDER and CBER have ap­proved over 150 new mol­e­c­u­lar en­ti­ties, new drug ap­pli­ca­tions and bi­o­log­ics li­cense ap­pli­ca­tions,” Hahn said, near­ly half of which have been for or­phan in­di­ca­tions.

Hahn added that in the most re­cent fis­cal year, FDA “reached a new high for pri­or­i­ty ap­pli­ca­tions filed — 72 — and to­tal ap­pli­ca­tions filed — 166 — and again are on track to meet or ex­ceed most of our re­view per­for­mance goals.”

Out­side of the re­view goals, Hahn said FDA has pub­lished more than 30 draft or re­vised guid­ances, held more than 20 pub­lic meet­ings and work­shops and pub­lished nine pub­lic re­ports as part of its PDU­FA VI com­mit­ments.

An­drew Kish

An­drew Kish, di­rec­tor, Of­fice of Pro­gram and Strate­gic Analy­sis at the Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) gave an overview of the pre­vi­ous PDU­FA pro­grams and not­ed the mod­ern­ized user fee struc­ture in the lat­est agree­ment.

“PDU­VA VI mod­ern­ized the user fee struc­ture to im­prove pro­gram fund­ing pre­dictabil­i­ty, sta­bil­i­ty and ad­min­is­tra­tive ef­fi­cien­cy. The new struc­ture elim­i­nat­ed the sup­ple­ment fees, re­placed es­tab­lish­ment and prod­uct fees with the pro­gram fee, which shift­ed a greater pro­por­tion of the tar­get rev­enue to the new, more pre­dictable, sta­ble, an­nu­al pro­gram fee,” Kish said.

Kish al­so point­ed out that user fees have ac­count­ed for an in­creas­ing por­tion of fund­ing for FDA’s new drug re­view pro­gram. “User fee rev­enue has out­paced bud­get au­thor­i­ty avail­able for the pro­gram. As a point of com­par­i­son, PDU­FA user fee rev­enue fund­ed 7% of the pro­gram in 1993 and as of 2019 it funds 71% of the pro­gram,” he said.

For PDU­FA VII, Kish laid out FDA’s four over­ar­ch­ing pri­or­i­ties for the pro­gram: pro­mote sus­tain­able in­no­va­tion in drug de­vel­op­ment; en­hance reg­u­la­to­ry pre­dictabil­i­ty and post­mar­ket safe­ty; ad­vance the reg­u­la­to­ry in­fra­struc­ture for dig­i­tal tech­nolo­gies and new sources of da­ta; and en­hance op­er­a­tional ca­pa­bil­i­ties, ef­fi­cien­cy and agili­ty.

In­dus­try wish list

Rep­re­sen­ta­tives from both the Phar­ma­ceu­ti­cal Re­search and Man­u­fac­tur­ers of Amer­i­ca (PhRMA) and the Biotech­nol­o­gy In­no­va­tion Or­ga­ni­za­tion (BIO) pre­sent­ed their re­spec­tive in­dus­tries’ goals for the next user fee agree­ment that will be hashed out in meet­ings with FDA over the com­ing months.

Both Lucy Vereshchag­i­na, vice pres­i­dent of sci­ence and reg­u­la­to­ry ad­vo­ca­cy at PhRMA, and Carti­er Es­ham, ex­ec­u­tive vice pres­i­dent, emerg­ing com­pa­nies at BIO, stressed that PDU­FA VII should glean from lessons learned dur­ing the COVID-19 pan­dem­ic.

“There is a press­ing need for FDA, and in­dus­try, to iden­ti­fy ac­tions tak­en dur­ing the COVID-19 pan­dem­ic and eval­u­ate their ef­fec­tive­ness and ap­plic­a­bil­i­ty to in­no­v­a­tive drug de­vel­op­ment be­yond the pub­lic health emer­gency,” Vereshchag­i­na said.

The phar­ma­ceu­ti­cal in­dus­try group would al­so like to see “More pre­dictable and time­ly en­gage­ment and bet­ter com­mu­ni­ca­tion dur­ing drug de­vel­op­ment,” Vereshchag­i­na said, not­ing the group’s de­sire for more risk-based in­spec­tions and en­hanced tech­no­log­i­cal in­fra­struc­ture at the agency.

Vereshchag­i­na al­so said that, “PhRMA would sup­port the es­tab­lish­ment of a flex­i­ble and scal­able glob­al frame­work for dig­i­tal tech­nol­o­gy de­vel­op­ment,” build­ing on ex­pe­ri­ence with a shift to telemed­i­cine and dig­i­tal health tech­nolo­gies dur­ing the pan­dem­ic.

Ad­di­tion­al­ly, Vereshchag­i­na stressed that PhRMA would like to see greater sup­port for re­al world ev­i­dence (RWE) in FDA’s de­ci­sion-mak­ing. “PhRMA be­lieves that re­al world ev­i­dence, for ex­am­ple, can be used for demon­strat­ing ef­fec­tive­ness ei­ther on its own in some cir­cum­stances or in com­bi­na­tion with oth­er da­ta,” she said.

Carti­er Es­ham

Speak­ing for BIO, Es­ham said the group has three main ob­jec­tives, on top of its “ever­green po­si­tion” sup­port­ing the agency’s abil­i­ty to hire and re­tain “world-class per­son­nel.”

Those ob­jec­tives, Es­ham said, are to “con­tin­ue to op­ti­mize the cur­rent pro­gram and process­es; to en­sure sci­ence-based and ef­fec­tive postap­proval re­quire­ments and ac­tiv­i­ties; and third, to de­vel­op new ini­tia­tives that will best pre­pare us for the fu­ture.”

For PDU­FA VII, Es­ham said BIO would like to see more fund­ing go­ing to the Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) to ac­com­mo­date the in­creased work­load around cell and gene ther­a­pies.

“With these prod­ucts comes in­creased de­mand on CBER re­sources, in­clud­ing ex­pert per­son­nel, ad­di­tion­al meet­ings and en­gage­ment with FDA,” Es­ham said.

BIO would al­so like fur­ther clar­i­fi­ca­tion on the ev­i­den­tiary stan­dards for FDA’s ex­pe­dit­ed path­ways such as the agency’s new re­gen­er­a­tive med­i­cine ad­vanced ther­a­py (RMAT) des­ig­na­tion, Es­ham said. FDA has grant­ed more than 50 RMAT des­ig­na­tions since the des­ig­na­tion’s cre­ation un­der the 21st Cen­tu­ry Cures Act, but has yet to ap­prove a sin­gle RMAT-des­ig­nat­ed prod­uct.

Es­ham al­so called for the es­tab­lish­ment of process­es and best prac­tices to im­prove the ef­fi­cien­cy and ef­fec­tive­ness of meet­ings be­tween spon­sors and FDA. “Best prac­tices can en­sure FDA-spon­sor in­ter­ac­tions are as ef­fi­cient as pos­si­ble and if prop­er­ly done, could serve to de­crease the amount of meet­ing re­quests,” she said. While FDA has gen­er­al­ly met most of its PDU­FA re­view per­for­mance goals over the last decade, it has fared less well with its meet­ing and com­mu­ni­ca­tions goals.

Ad­di­tion­al­ly, BIO would like to see FDA es­tab­lish new mech­a­nisms and time­lines for com­mu­ni­ca­tion with in­dus­try, such as pro­vid­ing an op­por­tu­ni­ty for spon­sors to ask clar­i­fy­ing ques­tions af­ter mile­stone meet­ings and set­ting struc­tured time­lines for com­mu­ni­ca­tion for la­bel­ing, post­mar­ket re­quire­ment (PMR) and post­mar­ket com­mit­ment (PMC) process­es and pe­di­atric study plans.

Es­ham added that it will be crit­i­cal­ly im­por­tant to “con­tin­ue to ad­vance mod­ern man­u­fac­tur­ing qual­i­ty and in­spec­tions method­ol­o­gy and process­es,” and called for risk-based ap­proach­es to preap­proval in­spec­tions.

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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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