FDA of­fi­cials, ex­perts dis­cuss im­pact of Covid-19 on cell and gene ther­a­pies

While the FDA is still re­ceiv­ing in­ves­ti­ga­tion­al new drug ap­pli­ca­tions (INDs) for cell and gene ther­a­pies, of­fi­cials are con­cerned about the im­pact of the Covid-19 pan­dem­ic on clin­i­cal tri­als.

Pe­ter Marks

“It’s clear that COVID-19 has ad­verse­ly af­fect­ed all as­pects of de­vel­op­ment of cell and gene ther­a­pies,” said CBER di­rec­tor Pe­ter Marks at the Al­liance for Re­gen­er­a­tive Med­i­cine’s Meet­ing on the Mesa. “For some of the stud­ies that are on­go­ing there are some re­al chal­lenges to over­come in terms of end­points that may have been missed.”

The pan­dem­ic al­so has dis­rupt­ed glob­al har­mo­niza­tion ef­forts around gene ther­a­pies, Marks said.

“We were on the cusp, in fact, work­ing with glob­al reg­u­la­tors try­ing to get to­wards more har­mo­niza­tion of gene ther­a­py pro­grams in dif­fer­ent coun­tries,” he said. “We’re try­ing to keep it mov­ing but it’s a chal­lenge to do.”

Marks not­ed that be­fore Covid-19 he spent about 75% of his time on cell and gene ther­a­pies, but the pan­dem­ic has forced him to shift pri­or­i­ties. “Some things have less pol­i­cy de­mands at this point in time. At this point in time it’s very much re­versed and it’s prob­a­bly 80% of my time on COVID-re­lat­ed ac­tiv­i­ties.”

Marks al­so not­ed that CBER’s Of­fice of Tis­sues and Ad­vanced Ther­a­pies (OTAT) has been strug­gling to keep up with its work­load even be­fore the pan­dem­ic. With the in­flux of ap­pli­ca­tions for cell and gene ther­a­pies over the last five years, Marks said the of­fice, “Should have dou­bled in size and it’s on­ly mod­est­ly larg­er, 15-20% larg­er in size.”

Marks said he is not sat­is­fied with the lev­el of di­a­logue the agency has been able to have with gene ther­a­py de­vel­op­ers. “Es­pe­cial­ly ear­ly on, we should be able to have this di­a­logue that re­al­ly fa­cil­i­tates set­ting things up well so that our knowl­edge of the en­tire field—we help lever­age that for every spon­sor.”

“We’ve been so strapped in terms of per­son­nel that it’s hard to do that,” Marks said, not­ing that Covid-19 has ex­ac­er­bat­ed things even fur­ther. “Be­cause the num­ber of gene ther­a­py ap­pli­ca­tions hasn’t fall­en off dra­mat­i­cal­ly, some of the tri­als may not be mov­ing as quick­ly, but the ap­pli­ca­tions keep com­ing in.” Marks said that OTAT has al­so had to shift pri­or­i­ties dur­ing the pan­dem­ic and that he hopes the next user fee cy­cle will bring in the re­sources nec­es­sary to staff up fur­ther.

Wil­son Bryan

Speak­ing on a sep­a­rate pan­el with mem­bers of in­dus­try, OTAT Di­rec­tor Wil­son Bryan echoed Marks’ sen­ti­ment.

“We were stretched thin be­fore the pan­dem­ic, and with the flood of work that came in, it re­al­ly had an im­pact,” he said. “Some­times folks don’t like to ad­mit this, but we all know we’ve had de­layed meet­ings, we’ve had to de­lay re­view of some ap­pli­ca­tions be­cause of giv­ing pri­or­i­ty to the pan­dem­ic.”

How­ev­er, Bryan said the of­fice is get­ting its bal­ance and is work­ing to catch up on some of its de­layed ac­tiv­i­ties.

Bryan ex­pressed some wor­ry about the fi­nan­cial well-be­ing of some of the small­er com­pa­nies his of­fice works with. “We’re hear­ing a lot about their strug­gles to stay afloat and con­tin­ue and fin­ish off their de­vel­op­ment pro­grams and whether or not those de­vel­op­ment pro­grams are go­ing to be suf­fi­cient to meet reg­u­la­to­ry stan­dards,” he said.

One of the chal­lenges, said Tim­o­thy Schroed­er, CEO of CTI Clin­i­cal Tri­al & Con­sult­ing, will be deal­ing with gaps in da­ta from clin­i­cal tri­als. “The ques­tion is go­ing to be how do spon­sors, how do reg­u­la­to­ry au­thor­i­ties and how do com­pa­nies such as our­selves fill those gaps?”

On the reg­u­la­tor side, Bryan said his of­fice is work­ing with com­pa­nies on an in­di­vid­ual ba­sis to sort out those is­sues, which dif­fer from one in­di­ca­tion to the next.

Bryan added that one pos­i­tive to come of the pan­dem­ic is greater in­ter­est in re­mote out­come as­sess­ments in clin­i­cal tri­als. “If we have an en­er­gy now to de­vel­op out­come mea­sures and val­i­date out­come mea­sures that al­low us to re­li­ably cap­ture in­for­ma­tion from pa­tients in re­mote lo­ca­tions, that will ul­ti­mate­ly fa­cil­i­tate de­vel­op­ment,” he said.

The pan­dem­ic al­so has sig­nif­i­cant­ly dis­rupt­ed FDA’s abil­i­ty to con­duct sur­veil­lance and preap­proval in­spec­tions. While the agency has re­sumed some do­mes­tic in­spec­tions and mis­sion-crit­i­cal for­eign in­spec­tions, it al­so is lever­ag­ing oth­er sources of in­for­ma­tion, in­clud­ing in­spec­tion re­ports from oth­er reg­u­la­tors, and re­quest­ing doc­u­ments from ap­pli­cants and fa­cil­i­ties in lieu of on-site in­spec­tions where pos­si­ble.

“We’re con­sid­er­ing vir­tu­al in­spec­tions, par­tic­u­lar­ly for com­pa­nies where the site has a track record, but if it’s a site that is brand new with no track record or if it’s a site with that has a bad track record, we’re hes­i­tant to do that,” Bryan said.

Bryan al­so raised the prospect of FDA in­spec­tors tag­ging along re­mote­ly for an in­spec­tion be­ing con­duct­ed by oth­er reg­u­la­tors. “Is it pos­si­ble that we could have an in­spec­tion by Eu­ro­pean in­spec­tors and have US reg­u­la­tors go­ing along for a vir­tu­al in­spec­tion at the same time? We think about those things, I don’t know that we’ve done them yet,” Bryan said, adding that he is not sure whether FDA in­spec­tors would be com­fort­able with the in­for­ma­tion they would get.

Cur­ran Simp­son

Cur­ran Simp­son, chief op­er­a­tions and tech­nol­o­gy of­fi­cer at Re­genxbio, said he sees promise in vir­tu­al au­dits and be­lieves the lev­el of doc­u­men­ta­tion a site pro­vides can be in­dica­tive of its com­pli­ance.

“How of­ten have I walked in­to a man­u­fac­tur­ing fa­cil­i­ty that’s well-run but has ter­ri­ble doc­u­men­ta­tion? Al­most nev­er. I think vir­tu­al au­dits, if you do a risk-based ap­proach and the au­dit part­ner has the abil­i­ty to send doc­u­men­ta­tion in an ef­fi­cient way and you have ex­pe­ri­enced peo­ple do­ing this, I think you’re go­ing to get the same fla­vor of an au­dit very quick­ly from the lev­el of the doc­u­men­ta­tion,” he said.

“Of course, you’ll want to ac­com­pa­ny that to the ex­tent pos­si­ble with imag­ing of the fa­cil­i­ty,” Simp­son said, “To see if those prac­tices are be­ing fol­lowed, the over­all clean­li­ness of the fa­cil­i­ty and the man­age­ment of ma­te­r­i­al move­ment … If you don’t get a good im­pres­sion from the doc­u­men­ta­tion that you’re work­ing through, it’s prob­a­bly a big­ger is­sue that you want to es­ca­late.”

Amy DuRoss

Amy DuRoss, co-founder and CEO of Vineti, an en­ter­prise soft­ware com­pa­ny spe­cial­iz­ing in ad­vanced ther­a­pies, ex­pressed some doubts about the cur­rent po­ten­tial for ful­ly re­mote au­dits.

“Cer­tain­ly our piece of the chain be­cause we’re en­ter­prise soft­ware is read­i­ly au­ditable re­mote­ly, but I would say that the over­all sys­tem and in man­u­fac­tur­ing, I’m not sure we’ve evolved as a species yet to adapt our re­mote tech­niques to get a full pic­ture … I don’t think we’re there yet,” she said.


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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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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.

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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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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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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George Church (courtesy EnPlusOne BioSciences)

George Church, Wyss sci­en­tists and North­pond chal­lenge con­ven­tion­al RNA man­u­fac­tur­ing with new biotech

RNA medicine has been at the forefront for the past few years, with the first RNA silencing therapy approved in 2018, and mRNA Covid vaccines following after. But flying under the radar has been the process of actually making RNA for these treatments.

That’s what Daniel Wiegand and Jonathan Rittichier have been working on in George Church’s lab for the past six years.

Friday morning, they unveiled EnPlusOne Biosciences, a biotech built on their RNA synthesis platform. Wiegand will serve as the Watertown, MA-based biotech’s CEO, and Rittichier will be CSO. And no different from his other startups, Church will be acting as scientific advisor. Its fourth co-founder, Dan Ahlstedt, joined through a Harvard Business School program, and will be COO.

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In­dus­try groups call to block WTO IP waiv­er ex­pan­sion to Covid-19 ther­a­peu­tics

The WTO’s TRIPS Council in mid-October is expected to debate whether to extend the IP waiver for Covid-19 vaccines to therapeutics and diagnostics too.

While the Biden administration backed the original vaccine waiver, which critics note has not done much to expand access to vaccines as demand has dried up, US trade officials haven’t offered any perspective yet on whether to expand the waiver to Covid treatments.