FDA re­leas­es PDU­FA VI pro­gram re­port on com­bi­na­tion prod­ucts

A new in­de­pen­dent re­port on the FDA’s re­view prac­tices for com­bi­na­tion prod­ucts un­der the Pre­scrip­tion Drug User Fee Act (PDU­FA VI) gives the agency gen­er­al­ly pos­i­tive marks but finds room for re­fine­ments in com­mu­ni­ca­tion and tech­nol­o­gy to im­prove the pre-sub­mis­sion and re­view process.

The re­port, com­mis­sioned by FDA as part of its PDU­FA VI com­mit­ments, was con­duct­ed by East­ern Re­search Group and looked at FDA staff and spon­sor ex­pe­ri­ences with com­bi­na­tion prod­ucts re­views dur­ing the pre-re­quest for des­ig­na­tion (pre-RFD), RFD, in­ter-cen­ter con­sult re­quest (IC­CR) and ap­pli­ca­tion sub­mis­sion stages.

FDA first de­tailed its pre-RFD pro­gram in draft guid­ance in 2017 be­fore fi­nal­iz­ing the guid­ance the fol­low­ing year. The pre-RFD process is in­tend­ed to al­low com­bi­na­tion prod­uct spon­sors a flex­i­ble, in­for­mal way to get feed­back about the iden­ti­ty or clas­si­fi­ca­tion of a med­i­c­i­nal prod­uct be­fore en­gag­ing in the for­mal RFD process.

Ac­cord­ing to the re­port, spon­sors and FDA staff found the pre-RFD and RFD process­es to be gen­er­al­ly “ef­fec­tive and ef­fi­cient de­spite some chal­lenges.” Spon­sors great­ly pre­ferred the pre-RFD route, with 46 pre-RFD and 3 RFD re­views com­plet­ed dur­ing the re­view pe­ri­od.

Spon­sors pre­ferred the pre-RFD process “for two main rea­sons: the pre-RFT process pro­vides more op­por­tu­ni­ties for in­ter­ac­tion with FDA, and sub­mis­sion re­quire­ments are more flex­i­ble.” The re­port al­so found that FDA need­ed to email spon­sors for more in­for­ma­tion for more than half (57%) of the pre-RFDs in or­der to have suf­fi­cient in­for­ma­tion to re­view.

Most of the re­quests for ad­di­tion­al in­for­ma­tion were “for fur­ther ex­pla­na­tion of how the prod­uct works and prod­uct com­po­nents, in­gre­di­ents, or spec­i­fi­ca­tions,” though the re­port notes that in some cas­es spon­sors may have been re­luc­tant to pro­vide in­for­ma­tion that would work against their “de­sired rec­om­men­da­tion for clas­si­fi­ca­tion and cen­ter as­sign­ment.”

The re­port al­so found the time from re­ceipt of a pre-RFD to ac­cep­tance for re­view ranged from 0-287 days with a mean and me­di­an time to ac­cep­tance of 27 and 9 days, re­spec­tive­ly. FDA typ­i­cal­ly re­spond­ed to pre-RFDs with­in its 60-day goal win­dow.

While some spon­sors said they ap­pre­ci­at­ed the op­por­tu­ni­ty to have in­for­mal tele­con­fer­ence calls via the pre-RFD process, some did not re­al­ize they had to re­quest the calls. FDA staff al­so point­ed out that the in­for­mal tele­con­fer­ences were, “Not worth­while if used by the spon­sor to present clin­i­cal da­ta out­side the scope of the pri­ma­ry mode of ac­tion de­ter­mi­na­tion or to ar­gue le­gal top­ics.”

The re­port had less to say about the RFD process, not­ing that FDA filed all three RFDs in the sam­ple with­in its goal of five busi­ness days af­ter re­ceipt and is­sued des­ig­na­tion let­ters with­in 60 cal­en­dar days.

When it came to in­ter-cen­ter co­or­di­na­tion, the re­port found the IC­CR process “was ef­fec­tive in en­abling the lead cen­ter to ob­tain in­for­ma­tion and ex­per­tise from the con­sult­ed cen­ter de­spite many in­stances of rec­om­mend­ed IC­CR process time­lines not be­ing met,” with de­lays main­ly at­trib­uted to tech­no­log­i­cal and com­mu­ni­ca­tion chal­lenges.

Just over half (56%) of IC­CRs from the Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) to the Cen­ter for De­vices and Ra­di­o­log­i­cal Health (CDRH) were sent with­in 7-14 days of ap­pli­ca­tion re­ceipt, with CDER at­tribut­ing the late sub­mis­sions to de­layed no­ti­fi­ca­tion from a lead cen­ter sub­mis­sion con­tact to the lead cen­ter con­sult re­questor and sub­mis­sions be­ing sent to the wrong group in CDRH.

“Sub­se­quent­ly, CDRH as­signed 53% of IC­CRs to re­view­ers with­in 2-3 days of IC­CR form sub­mis­sion; be­cause 44% of ICR forms were sub­mit­ted lat­er than rec­om­mend­ed, this meant that CDRH as­signed 38% of the IC­CRs to re­view­ers with­in the rec­om­mend­ed 9-17 days of ap­pli­ca­tion re­ceipt,” the re­port finds.

“When CDRH took more than 2-3 days to as­sign re­view­ers to IC­CRs, staff at­trib­uted de­lays to in­suf­fi­cient in­for­ma­tion in the IC­CR form to de­cide who best to re­spond … and in­con­sis­tent ac­cess to lead cen­ter data­bas­es to re­view de­tails need­ed to as­sign the IC­CR.”

On the whole, the re­port finds that CDRH on­ly com­plet­ed one-third (34%) of IC­CRs by the date re­quest­ed by CDER, though CDER staff re­port­ed that IC­CR prac­tices were, “rea­son­ably smooth, time­ly, and high qual­i­ty once CDRH as­signed a re­view­er.” CDER staff al­so point­ed to a switch from a Share­Point-based sys­tem to a Sales­force-based sys­tem as a ma­jor source of in­ef­fi­cien­cy in the process.

CDRH staff, on the oth­er hand, char­ac­ter­ized the IC­CR process as “ad­e­quate­ly ef­fi­cient,” cit­ing dif­fi­cul­ties ac­cess­ing da­ta from CDER data­bas­es that slowed things down.

As for the sub­mis­sion and re­view of new drug ap­pli­ca­tions (NDAs), bi­o­log­ics li­cense ap­pli­ca­tions (BLAs) and in­ves­ti­ga­tion­al new drug ap­pli­ca­tions (INDs), the re­port finds most were “gen­er­al­ly sim­i­lar to those for non­com­bi­na­tion prod­uct ap­pli­ca­tions.”


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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.

#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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 151,400+ biopharma pros reading Endpoints daily — and it's free.