The Sarep­ta dilem­ma: Bioethics ex­pert Arthur Ca­plan says it’s time to re­think how to reg­u­late com­pas­sion

Arthur Ca­plan was nev­er en­thu­si­as­tic about the idea of an FDA ap­proval for Ex­ondys 51 (eteplirsen) for Duchenne mus­cu­lar dy­s­tro­phy. When it came through, the not­ed NYU bioethics ex­pert saw it as a de­vi­a­tion from the FDA’s poli­cies on how drugs should be stud­ied and re­viewed, fo­cus­ing on safe­ty and a clear sig­nal of ef­fi­ca­cy.

But there were a lot of things wrong with it.

“The tri­al was poor,” Ca­plan tells me, “and even with small num­bers I think it could have been done bet­ter.” The ve­he­ment pub­lic lob­by­ing by Duchenne fam­i­lies to get it across the fin­ish line al­so didn’t con­vince him that the agency need­ed to make it avail­able.

“Some­times, peo­ple see what they want to see,” he says. “And some­times they’re right. It’s an iffy ba­sis for ap­prov­ing things.”

But this isn’t a sto­ry about a promi­nent bioethi­cist ob­ject­ing to the FDA’s con­tro­ver­sial rul­ing, which hinged en­tire­ly on Janet Wood­cock’s will­ing­ness to over­ride her col­leagues.

At this point, says Ca­plan, de­bat­ing over whether the FDA should or should not have ap­proved the drug is dis­tract­ing from the re­al is­sues at hand. Sarep­ta, he says, was a shot across the bow of the FDA and bio­phar­ma.

“Let’s use the Sarep­ta bat­tle to re­vis­it where we are with com­pas­sion­ate use, what con­sti­tutes ev­i­dence, what will be ac­cept­ed as ev­i­dence and who pays for col­lec­tion of the ev­i­dence and ul­ti­mate­ly ear­ly ac­cess,” says Ca­plan.

Be­cause the next Sarep­ta will be right around the next cor­ner. Fol­lowed by the next, the next and.…

“The FDA should be think­ing hard about this,” says Ca­plan. “This is the first in what will be a long pa­rade of dis­eases that af­fects small num­bers of pa­tients.

“We’re try­ing to bal­ance the chal­lenge of com­pas­sion­ate use against ap­proval and I think we have to re­vis­it the whole sub­ject,” says Ca­plan. “This is a trig­ger to re-ex­am­ine what are we go­ing to do down the road. Are ex­pand­ed ac­cess guide­lines ad­e­quate? Is it time to start re­think­ing what sort of in­for­ma­tion can be pro­vid­ed as ev­i­dence? What about ul­tra rare dis­eases, where the num­bers are small?   What should reg­u­la­tors ex­pect in terms of ‘ev­i­dence’”

Just con­sid­er gene ther­a­py, which is tar­get­ing path­ways where the num­bers are of­ten tiny.

“We have to start to re­think what con­sti­tutes ‘ad­e­quate’ and ‘suf­fi­cient’ ev­i­dence,” do we need more manda­to­ry ex­ten­sive Phase 4 mon­i­tor­ing than now oc­curs he says.

How should de­vel­op­ers and the FDA think about eval­u­at­ing hope­ful ear­ly signs of ef­fi­ca­cy? What tar­gets should you go af­ter? Where should sur­ro­gate end­points play a big role?

“To­day’s tri­al de­signs are not up to what has been ex­pect­ed in terms of ev­i­dence,” says Ca­plan, “and do­ing this on the fly doesn’t make a lot of sense.”

The FDA is be­hind the curve on where the sci­ence is and where con­sumer pres­sures are be­ing ap­plied. If they had been up to speed, says Ca­plan, Sarep­ta could have been guid­ed much ear­li­er to pro­vide more rel­e­vant da­ta with what they had.

“I don’t think they col­lect­ed enough sys­tem­at­ic in­for­ma­tion,” says the ethi­cist. “The FDA might have de­mand­ed more ear­li­er. The com­pa­ny could have done more.”

And how can you even run tri­als when a drug is made avail­able ear­ly to small pa­tient groups with very rare dis­eases through com­pas­sion­ate use, which might be a bet­ter way to go for pa­tients than a place­bo tri­al?

Un­der the old so­cial con­tract be­tween drug com­pa­nies and pa­tients, says Ca­plan, if pa­tients were will­ing to run the risk of be­ing in the con­trol arm, they could sign up for a tri­al to help prove if a drug worked or not — and might get it. In the process, they were will­ing to take a big risk to gain ac­cess and help the process of drug de­vel­op­ment.

That kind of arrange­ment no longer works for pa­tients.

“The new deal is, I want the drug,” says Ca­plan, “I want to help me. So pa­tient groups praise these new drugs, say­ing every­thing is great, I want the drug.”

And they don’t want to be left pay­ing for it out of pock­et, ei­ther, es­pe­cial­ly if you’re talk­ing about a $300,000 a year bill for a rare dis­ease ther­a­py like Ex­ondys 51. But then, nei­ther do in­sur­ers like An­them, which an­nounced late last week that they wouldn’t re­im­burse for a drug the in­sur­er has de­ter­mined is still ex­per­i­men­tal.

“Of course it’s an ex­per­i­men­tal drug,” Ca­plan re­sponds. “They’re not go­ing to be bound by that kind of an FDA de­ci­sion un­til they think there’s ad­e­quate ev­i­dence. And this is es­pe­cial­ly true since it’s very ex­pen­sive.”

So who does pay for these? Of­ten, small biotechs like Sarep­ta can’t af­ford to pay. So when Ca­plan hears state and Fed­er­al law­mak­ers talk about the right to try, he won­ders why they don’t im­me­di­ate­ly start dis­cussing how they pro­pose to pro­vide the funds to pay for it.

That’s an­oth­er part of the dis­cus­sion that’s miss­ing in ac­tion in this de­bate, says the ethi­cist. And it’s past time for the in­dus­try, the FDA, law­mak­ers and pa­tient groups to grap­ple with the re­al­i­ty of cost and all the sci­en­tif­ic is­sues now.

Time has run short for tak­ing a com­pre­hen­sive look at one of the most dif­fi­cult top­ics in the in­dus­try—how best to reg­u­late com­pas­sion.

IDC: Life Sci­ences Firms Must Em­brace Dig­i­tal Trans­for­ma­tion Now

Pre-pandemic, the life sciences industry had settled into a pattern. The average drug took 12 years and $2.9 billion to bring to market, and it was an acceptable mode of operations, according to Nimita Limaye, Research Vice President for Life Sciences R&D Strategy and Technology at IDC.

COVID-19 changed that, and served as a proof-of-concept for how technology can truly help life sciences companies succeed and grow, Limaye said. She recently spoke about industry trends at Egnyte’s Life Sciences Summit 2022. You should watch the entire session, free and on-demand, but here’s a brief recap of why she’s urging life sciences companies to embrace digital transformation.

Martin Landray, Protas CEO (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Those big bil­lion-dol­lar PhI­II stud­ies? Mar­tin Lan­dray says they can be done for a tiny frac­tion of the cost

Martin Landray knows what controversy in clinical drug development feels like, from first-hand experience.

Landray was the chief architect of RECOVERY, a study that pitted a variety of drugs against Covid-19. And he offered some landmark data that would help push dexamethasone out into broader use as a cheap treatment, while helping ice hydroxy’s reputation as a clear misfire.

“Lots of people told us we shouldn’t use it,” Landray says about dexamethasone and Covid-19. “It was dangerous. We shouldn’t even do a trial. They also cared about hydroxychloroquine and lots of people said we shouldn’t do a trial because it must be used. I’ve got the letters from both sets of people.”

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Geoffrey Porges, new Schrödinger CFO

Long­time an­a­lyst Ge­of­frey Porges de­parts SVB to lead fi­nances at a drug dis­cov­ery shop

Geoffrey Porges has ended his two-decade run as a biotech analyst, as the former SVB Securities vice chair began as CFO of Schrödinger on Thursday.

The long-running analyst, who previously headed up vaccines marketing at Merck before the turn of the millennium, will lead the financial operations of the 700-employee company as Schrödinger broadens its focus from a drug discovery partner to also building out an in-house pipeline, with clinical trial No. 1 set to begin next quarter.

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FDA ap­proves one of the prici­est new treat­ments of all time — blue­bird's gene ther­a­py for be­ta tha­lassemia

The FDA on Wednesday approved the first gene therapy for a chronic condition — bluebird bio’s new Zynteglo (beti-cel) as a potentially curative treatment for those with transfusion-dependent thalassemia.

The thumbs-up from the FDA follows a unanimous adcomm vote in June, with outside experts pointing to extraordinary efficacy, with 89% of subjects with TDT who received beti-cel having achieved transfusion independence.

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James Mock, incoming CFO at Moderna

Mod­er­na taps new CFO from PerkinElmer af­ter for­mer one-day CFO oust­ed

When Moderna hired a new CFO last year,  it didn’t expect to see him gone after only one day. Today the biotech named his — likely much more vetted — replacement.

The mRNA company put out word early Wednesday that after the untimely departure of then brand-new CFO Jorge Gomez, it has now found a replacement in James Mock, the soon-to-be former CFO at diagnostics and analytics company PerkinElmer.

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Bayer's first DTC ad campaign for chronic kidney disease drug Kerendia spells out its benefits

Bay­er aims to sim­pli­fy the com­plex­i­ties of CKD with an ABC-themed ad cam­paign

Do you know the ABCs of CKD in T2D? Bayer’s first ad campaign for Kerendia tackles the complexity of chronic kidney disease with a play on the acronym (CKD) and its connection to type 2 diabetes (T2D).

Kerendia was approved last year as the first and only non-steroidal mineralocorticoid receptor antagonist to treat CKD in people with type 2 diabetes.

In the TV commercial launched this week, A is for awareness, B is for belief and C is for cardiovascular, explained in the ad as awareness of the connection between type 2 and kidney disease, belief that something can be done about it, and cardiovascular events that may be reduced with treatment.

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Joe Jonas (Photo by Anthony Behar/Sipa USA)(Sipa via AP Images)

So­lo Jonas broth­er car­ries Merz's new tune in Botox ri­val cam­paign

As the lyrics of his band’s 2019 pop-rock single suggest, Joe Jonas is only human — and that means even he gets frown lines. The 33-year-old singer-songwriter is Merz’s newest celebrity brand partner for its Botox rival Xeomin, as medical aesthetics brands target a younger audience.

Merz kicked off its “Beauty on Your Terms” campaign on Tuesday, featuring the Jonas brother in a video ad for its double-filtered anti-wrinkle injection Xeomin.

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Marisol Peron, Genmab SVP of communications and corporate affairs

Gen­mab launch­es cor­po­rate cam­paign am­pli­fy­ing its ‘knock your socks off’ an­ti­bod­ies

Genmab often talks about its “knock-your-socks-off” antibodies — and now the term is getting its own logo and corporate campaign.

The teal and purple logo for the acronym KYSO — Genmab pronounces it “ky-so” — debuts on Wednesday and comes on the heels of Genmab’s newly announced 2030 vision. That aspiration aims to expand Genmab’s drug development beyond oncology to include other serious diseases, while also doubling down on its own drug development.

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Joel Dudley, new partner at Innovation Endeavors (Bosch Health Campus)

For­mer Google CEO’s VC is mak­ing a big­ger push in­to the biotech world, hir­ing promi­nent Ther­a­nos skep­tic

Venture capital firm Innovation Endeavors has mainly had its focus on investments across the tech space, but it has been slowly turning its attention to the biotech world. Now, a new partner is coming into the fold showing that its interest in biotech is likely to grow further.

The Silicon Valley-based company, which is headed up by former Google CEO Eric Schmidt, has brought on Joel Dudley as a partner. According to Dudley’s LinkedIn page, he is joining Innovation Endeavors after serving as the chief science officer of biotech startup Tempus Labs since 2020.

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