Peter Marks (Greg Nash/Pool via AP)

Even FDA's Pe­ter Marks is wor­ried about the com­mer­cial vi­a­bil­i­ty of gene and cell ther­a­pies

When blue­bird bio’s gene ther­a­py to treat be­ta tha­lassemia won Eu­ro­pean ap­proval in 2019, the near­ly $2 mil­lion per pa­tient price tag for the po­ten­tial cure seemed like a sur­mount­able hur­dle.

Fast for­ward two years lat­er, and blue­bird has with­drawn Zyn­te­glo, the be­ta thal drug, along with the rest of its gene ther­a­py port­fo­lio from Eu­rope, which the com­pa­ny said is gen­er­al­ly un­will­ing to pay a fair price for the treat­ment.

In Ger­many, the on­ly coun­try for which blue­bird dis­closed de­tails, au­thor­i­ties of­fered $790,000 for the one-time treat­ment, with the pay­out mov­ing to $950,000 if the ther­a­py is still work­ing af­ter five years. That’s rough­ly in line with the $900,000 price tag Wall Street an­a­lysts ex­pect­ed blue­bird to put on the ther­a­py pri­or to launch. But blue­bird want­ed $1.8 mil­lion paid over 5 years, with pay­outs con­di­tioned on a pa­tient’s re­sponse.

This and oth­er ex­am­ples (see Gly­bera) have raised ques­tions about the vi­a­bil­i­ty of the gene and cell ther­a­py space, par­tic­u­lar­ly as it’s able to tar­get small­er and small­er groups of pa­tients.

Pe­ter Marks, di­rec­tor of the cen­ter at FDA that reg­u­lates these ther­a­pies, ad­dressed this is­sue of fi­nan­cial vi­a­bil­i­ty head on at a con­fer­ence on Tues­day morn­ing, par­tic­u­lar­ly as it re­lates to in­di­ca­tions where there may on­ly be sev­er­al dozen pa­tients world­wide.

The prob­lem is spon­sors are see­ing this group of on­ly 20 to 40 pa­tients per year for one ther­a­py as com­mer­cial­ly non­vi­able, Marks ex­plained. If there was bet­ter man­u­fac­tur­ing of small­er batch­es of AAV vec­tors for gene ther­a­pies, for ex­am­ple, he said, there might be a way to put to­geth­er a port­fo­lio of these small­er-pop­u­la­tion prod­ucts that would then be vi­able.

While it’s un­ortho­dox for any se­nior FDA of­fi­cial to ad­dress the com­mer­cial vi­a­bil­i­ty of any med­ical prod­ucts, and the FDA re­cent­ly ad­dressed some of the safe­ty ques­tion marks around gene and cell ther­a­pies, Marks specif­i­cal­ly ad­dressed these small­er groups of gene ther­a­pies, not­ing, “We’re all a lit­tle gun-shy when we see pro­grams be­ing dropped, and that means we have to find a way for­ward to re­store con­fi­dence for these small­er pop­u­la­tions.”

Part of the path for­ward in­cludes fig­ur­ing out how to price these ex­pen­sive and ex­pen­sive-to-make ther­a­pies, he said.

“Re­im­burse­ment is the 800 pound go­ril­la in the room,” Marks told the crowd vir­tu­al­ly on Tues­day at the AS­GCT’s 25th an­nu­al meet­ing in Wash­ing­ton, DC, not­ing that some of the ac­cel­er­at­ed ap­provals “make peo­ple shud­der be­cause of con­cerns” about pric­ing and risk-shar­ing mod­els.

“Once there are 5 to 8 gene ther­a­pies, things will work them­selves out,” Marks added, of­fer­ing the ex­am­ple of No­var­tis’ spinal mus­cu­lar at­ro­phy gene ther­a­py Zol­gens­ma as a case where:

the val­ue propo­si­tion is so over­whelm­ing, it’s hard to think of not to cov­er that. But for oth­ers, where it’s not a life or death is­sue, it will be more chal­leng­ing and will be sim­i­lar to what our Eu­ro­pean col­leagues see. How that gets re­solved will com­plete­ly af­fect how many peo­ple go in­to this field to de­vel­op ther­a­pies.

He al­so sug­gest­ed a much more in­ter­na­tion­al­ly har­mo­nized ap­proach for reg­u­lat­ing these gene ther­a­pies for small­er, rare dis­ease pa­tient groups, which might have dozens of pa­tients glob­al­ly.

Marks sug­gest­ed a way to move to a more com­mon ap­pli­ca­tion process glob­al­ly, not­ing, “Maybe we won’t get some of the pre­clin­i­cal in­fo we do care about, but can live with­out, and in turn, pa­tients get ac­cess in home coun­tries with­out hav­ing to trav­el” to gain ac­cess to these ther­a­pies. “We have to give se­ri­ous con­sid­er­a­tion to these prod­ucts. If it’s de­signed to 10-20 per 100 mil­lion peo­ple, any one coun­try won’t have enough pa­tients to sus­tain com­mer­cial­iza­tion,” he said.

Marks pre­vi­ous­ly penned an NE­JM ed­i­to­r­i­al on these in­di­vid­u­al­ized treat­ments and how to reg­u­late them in 2019.

On ques­tions re­lat­ed to ac­cel­er­at­ed ap­proval re­forms, which have been in the news as Con­gress at­tempts to tack sev­er­al of these re­forms on­to must-pass FDA user fee leg­is­la­tion, Marks said there’s a need for the AA path­way in the cell and gene ther­a­py space. Some neu­rode­gen­er­a­tive dis­eases, for in­stance, he said, “If we take away the abil­i­ty to use sur­ro­gate end­points, we would have a lot of trou­ble see­ing these prod­ucts de­vel­oped.”

But he did ac­knowl­edge that the ac­cel­er­at­ed ap­proval path­way “has been used like an off-ramp” lead­ing to prob­lems in the past.

“Sur­pris­es are not need­ed here in the gene ther­a­py field. The idea here is agree­ing up­front on the sur­ro­gate, there’s less a chance for sur­pris­es. What we will be do­ing is mov­ing these dis­cus­sions up­front,” Marks said.

In re­sponse to a ques­tion from the au­di­ence on what the timetable might look like for get­ting back to tele­con­fer­enc­ing be­tween CBER and spon­sors, Marks ac­knowl­edged the staff short­ages and that this “is not an op­ti­mal sit­u­a­tion. Even pri­or to the pan­dem­ic, we were un­der­staffed. My key for 2022 is a re­cov­ery theme — my hope is that as we ease in­to the next cal­en­dar year, more ro­bust ex­changes with the agency oc­cur, in­clud­ing tele­con­fer­ences.”

Paul Hudson, Sanofi CEO (Cyril Marcilhacy/Bloomberg via Getty Images)

FDA side­lines Paul Hud­son's $3.7B MS drug af­ter es­tab­lish­ing link to liv­er dam­age

One of Sanofi CEO Paul Hudson’s top picks in the pipeline — picked up in a $3.7 billion buyout 2 years ago — has just been sidelined in the US by a safety issue.

The pharma giant put out word early Thursday that the FDA has put their Phase III studies of tolebrutinib in multiple sclerosis and myasthenia gravis on partial clinical hold, halting enrollment and suspending dosing for patients who have been on the drug for less than 60 days. Patients who have completed at least 60 days of treatment can continue therapy as researchers explore a “limited” — but unspecified in Sanofi’s statement — number of cases of liver injury.

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Phar­ma re­acts to post-Roe; Drug­mak­ers beef up cy­ber de­fense; Boehringer, Roche qui­et­ly axe drugs; 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.

As a reminder, we are off on Monday for the Fourth of July. I hope this recap will kick off your (long) weekend well and that the rest of it will be just what you need. See you next week for a shortened edition!

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Eric Hughes, incoming Teva EVP of global R&D and CMO

Te­va chief raids Ver­tex for his new glob­al head of re­search and de­vel­op­ment

Teva CEO Kåre Schultz has found his new R&D chief and CMO in Vertex’s ranks.

The global generics giant, which has some 3,500 staffers in the R&D group, has named Eric Hughes to the top research spot in the company. He’ll be replacing Hafrun Fridriksdottir, who held the role for close to five years, on Aug. 1.

Hughes hasn’t been at Vertex for long, though. He jumped from Novartis less than a year ago, after heading the immunology, hepatology & dermatology global development unit. Before that, he completed a five-year stint as head of early clinical research for the specialty discovery medicine department in the exploratory clinical & translational research group at Bristol Myers Squibb, according to his LinkedIn profile.

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#BIO22: Man­ag­ing a biotech in tur­bu­lent times. 'There's a per­fect shit­show out there'

On Tuesday, June 14, Endpoints News EIC John Carroll sat down with a group of biotech execs to discuss the bear market for industry stocks and how they were dealing with it. Here’s the conversation, which has been lightly edited for brevity.

Martin Meeson, sponsor opening:

Thank you, John. Hello everyone. My name’s Martin Meeson, I’m the CEO of Fujifilm Diosynth. For those of you who don’t know Fujifilm Diosynth, we operate in the development of clinical and commercial product scale up, we have facilities in Europe and the US, and around about 4,000 employees. We run on average about 150 programs, so when it comes to managing in turbulent times over the last two years, we’ve had quite a lot of experience of that. Not just keeping the clinical pipelines and the commercial pipelines open, but also our response to the pandemic and the molecules that we’ve had within there. One of the phrases that I coined probably about a year ago when we were talking at JP Morgan, was I talked about managing through turbulent times. Well, it’s become the fact that we are not managing and leading through these times, we are managing in them, which is why that’s really the purpose of and the topic that we’ve got today.

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Emer Cooke, ICRMA chair (AP Photo/Geert Vanden Wijngaert)

ICM­RA to launch sev­er­al reg­u­la­to­ry pi­lot pro­grams cen­tered around man­u­fac­tur­ing in­spec­tions

As regulatory agencies look to catch up on inspections amid the Covid-19 pandemic, ICMRA is unveiling several pilot programs to address industry applications and inspections.

ICMRA, which is made up of the world’s top drug regulators, is launching multiple pilot programs, including two regulatory pilots addressing facility inspections for chemistry and manufacturing controls (CMC) and post-approval change (PAC) submission assessments and related regulatory actions.

Bo Cumbo, AavantiBio CEO

Scoop: A small gene ther­a­py biotech, flush with ex-Sarep­ta and blue­bird lead­ers, guts CMC

En route to entering the clinic with its first AAV-based gene therapy for a rare neuromuscular disease, AavantiBio has let go of 30 employees, Endpoints News has learned.

The move comes after a year stacking its executive bench with ex-Sarepta and bluebird bio leaders and inking multiple partnerships with the likes of Aldevron, Catalent and Resilience. The biotech also formed a scientific advisory board in February.

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FDA slaps warn­ing let­ter on Min­neso­ta API fa­cil­i­ty af­ter em­ploy­ee de­stroys clean­ing log

A manufacturing facility belonging to the Netherlands-based API producer Fagron Group has entered the FDA’s crosshairs after an employee destroyed a cleaning log, among other violations.

One of its plants in Saint Paul, MN received a warning letter on June 14, following an inspection last November that uncovered cross-contamination concerns.

“In your response, you provided a follow-up cleaning validation report in which you only assessed the carryover of niacin swab samples but not progesterone, which was included in your initial cleaning validation,” FDA says in the letter. “The lack of progesterone (b)(4) [commercially confidential information] is concerning considering the failing residue results you provided to investigators would yield unacceptable levels of progesterone cross-contamination.”

Amgen's taking social media followers around the globe as it introduces the many different

From Tam­pa to Mu­nich, Am­gen’s ‘Places’ cam­paign in­tro­duces its lo­ca­tions around the world

Amgen is taking social media followers around the world with its latest corporate campaign. Called “Places of Amgen,” the twice monthly posts highlight the biopharma’s different offices and sites – and the people who work there.

Each post runs on LinkedIn, Facebook and Instagram with details about the work Amgen does in that location, when it was established, comments from people who work there and other interesting facts. The most recent one about Paris, France, for example, notes that Amgen France last year signed a French association charter committed to the inclusion of LBGT+ people in the workplace.

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On Friday, Lonza announced plans to construct a large-scale commercial drug product fill and finish facility in the town of Stein, Switzerland.

Lon­za to in­vest $500M+ on fill-fin­ish fa­cil­i­ty on its home turf

Lonza has been expanding its reach across the globe, bringing sites in China and the US online this year, but now they are looking closer to home for their next major investment.

The Swiss manufacturer on Friday announced plans to construct a large-scale commercial drug fill and finish facility in the town of Stein, Switzerland. The new facility will be delivered through an investment of approximately CHF 500 million, or $519 million, and is expected to be completed in 2026. The facility will also be constructed on the same campus as Lonza’s current clinical drug product facility.