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.

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Warren Huff, Reata CEO

Rea­ta sug­gests Friedre­ich's atax­ia pro­gram could be de­layed, send­ing stock plung­ing

Reata Pharmaceuticals $RETA made waves last October when its drug omaveloxolone produced positive trial results in treating a rare neurological disorder, but the candidate’s path forward became much murkier Monday.

In a report of quarterly earnings, the biotech divulged that the FDA is considering delaying omaveloxolone’s NDA pending completion of a second trial. That could push back approval by at least a year given that the target population, individuals with Friedreich’s ataxia, is limited and progression of the hard-to-treat illness is notoriously slow. The Covid-19 pandemic would also hinder Reata’s ability to complete an additional trial.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.

Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.

Vi­da Ven­tures co-leads Dyne's $115M megaround for next-gen oli­go ther­a­pies aimed square­ly at mus­cles

Dyne Therapeutics started out last April with a modest $50 million to mine targeted muscle disease therapies from its in-house conjugate technology. The biotech has now convinced more investors that it’s got gems on its hands, closing $115 million in fresh financing to push its next-gen oligonucleotide drugs into the clinic.

Vida Ventures and Surveyor Capital led the round, joined by a group of other new backers including Wellington Management Company, Logos Capital and Franklin Templeton.

Eli Lil­ly teams with Pieris on HER2+ tu­mors; Op­di­vo + Yer­voy best chemo in mesothe­lioma

Despite the FDA putting a partial clinical hold on its lead program only a few weeks ago, Boston-based Pieris Pharmaceuticals is plowing forward with a new collaboration.

Pieris will work with Eli Lilly to further advance studies on PRS-343, a 4-1BB/HER2 bispecific for HER2-positive tumors, in combination with the latter’s ramucirumab and paclitaxel for the second-line treatment of patients with HER2-positive gastric cancer in a single-arm, Phase II study.

In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

China-based Innovent Biologics and its multinational ally Eli Lilly shared Phase III evidence that their PD-1 inhibitor combo can delay the progression of nonsquamous non-small cell lung cancer.

But the drugmakers will face stiff competition in China from Merck’s Keytruda, the ruling PD-1 which is already approved to treat both squamous and nonsquamous NSCLC and boasts positive overall survival rates.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 86,800+ biopharma pros reading Endpoints daily — and it's free.