Are drug R&D costs ex­ag­ger­at­ed for ef­fect? Re­searchers peg the me­di­an price of piv­otal suc­cess at an eco­nom­i­cal $19M

One of the most fre­quent­ly cit­ed stats in the biotech biz re­volves around the claim that it can take more than a decade and $1 bil­lion-plus to get a drug to mar­ket. For lob­by­ists, it’s a chance to un­der­score the high cost of R&D that goes in­to a new treat­ment — and help con­sumers and pay­ers swal­low the bit­ter pill that comes with big prices at­tached to the ther­a­pies that pass muster at the FDA.

But does it ac­cu­rate­ly rep­re­sent the true cost of R&D to­day?

One set of re­searchers de­cid­ed to take a telling snap­shot of one key met­ric in drug de­vel­op­ment, and you might be sur­prised to learn what they found.

Joseph Ross

Pub­lish­ing in JA­MA In­ter­nal Med­i­cine, the group sized up the 138 piv­otal tri­als that were need­ed to get an ap­proval on 59 nov­el drugs ap­proved in 2015 and 2016. They used a glob­al clin­i­cal tri­al cost as­sess­ment tool used by CROs and phar­mas to make their es­ti­mates. 

The me­di­an es­ti­mat­ed cost of the full range of stud­ies: $19 mil­lion.

The spread start­ed at a low of $5 mil­lion for some very small stud­ies test­ing drugs for very rare dis­eases — with no con­trol group — and soared to $346.8 mil­lion for a non-in­fe­ri­or­i­ty study. Of the 138 to­tal, 26 were un­con­trolled, which is def­i­nite­ly cheap­er. The mean es­ti­mat­ed cost of those un­con­trolled stud­ies was $13.5 mil­lion com­pared to $35.1 mil­lion for a place­bo con­trol or ri­val drug in the mix.

The mantra in the biotech in­dus­try in par­tic­u­lar — where you’ll find the small­est R&D bud­gets — has been small­er, faster, cheap­er when it comes to stud­ies. And that mantra may be play­ing out in new tri­al de­signs that are squeez­ing the cost of clin­i­cal tri­als, par­tic­u­lar­ly for tru­ly nov­el drugs.

The au­thors say the num­bers pro­vide “a dif­fer­ent per­spec­tive to the wide­ly held as­sump­tion that elab­o­rate and ex­pen­sive clin­i­cal tri­als are the main rea­son for the high costs of de­vel­op­ing a new drug.”

In a com­men­tary, Yale’s Joseph Ross cau­tioned against con­sid­er­ing the study a guide to de­vel­op­ment costs, as it’s re­strict­ed to the suc­cess­ful piv­otal tri­als. He adds:

(I)t sug­gests that the stronger the ev­i­dence that is gen­er­at­ed, which is most use­ful to in­form clin­i­cal prac­tice, the more it costs. We get what we pay for, and high qual­i­ty clin­i­cal tri­al da­ta are well worth the in­vest­ment to make sure we pri­or­i­tize spend­ing our health­care re­sources on ther­a­pies that have been shown to ben­e­fit pa­tients.

PhRMA took a look at these num­bers, though, and im­me­di­ate­ly bris­tled at the im­pli­ca­tions. The study, says a spokesper­son, ig­nores the full range of costs that go in­to de­vel­op­ing a new drug, from pre­clin­i­cal through ap­proval. And what about all the fail­ures com­pa­nies have to en­dure along the way? That adds enor­mous­ly to the cost of drug de­vel­op­ment, says a spokesper­son.

This study’s nar­row find­ings should not be used to make sweep­ing gen­er­al­iza­tions about the in­vest­ment bio­phar­ma­ceu­ti­cal com­pa­nies make in the de­vel­op­ment of new ther­a­pies. The study ig­nores the ma­jor­i­ty of costs re­lat­ed to the re­search and de­vel­op­ment (R&D) of a new med­i­cine, rang­ing from ex­ten­sive pre-clin­i­cal re­search, clin­i­cal tri­als, glob­al co­or­di­na­tion of clin­i­cal tri­als, de­vel­op­ment of man­u­fac­tur­ing meth­ods and mul­ti­ple oth­er as­pects of de­vel­op­ment, sug­gest­ing a nar­row view of the R&D process and risk com­pa­nies face at the out­set of an un­cer­tain project.

More fun­da­men­tal­ly, the study ex­cludes the sig­nif­i­cant cost as­so­ci­at­ed with un­suc­cess­ful drug can­di­dates and tri­als. De­vel­op­ing in­no­v­a­tive new med­i­cines is a long and com­plex process fraught with more set­backs than suc­cess­es. Less than 12 per­cent of med­i­cines en­ter­ing a phase one clin­i­cal tri­al will ul­ti­mate­ly be ap­proved for use by pa­tients. Set­backs are an in­evitable part of the R&D process, and they must be fac­tored in­to the cost of dis­cov­er­ing new med­i­cines.

Maybe the moral to this sto­ry is that fail­ure is pricey, but late-stage suc­cess can be rel­a­tive­ly cheap. And that puts a dif­fer­ent spin on the big val­ues we’ve been see­ing for ex­per­i­men­tal drugs with some hu­man da­ta to back them up.

 

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Deborah Dunsire

The fourth CGRP mi­graine drug is here. Time for Lund­beck to prove it's worth $2B

They may be late, but Lundbeck is now officially in the game for preventing migraine with CGRP drugs.

The FDA has OK’d eptinezumab, the prize in Lundbeck’s $2 billion acquisition of Alder. Like rival offerings from Amgen/Novartis, Eli Lilly and Teva, the antibody blocks the calcitonin gene-related peptide, which is believed to dilate blood vessels in the brain and cause pain.

It will now be sold as Vyepti. The company has yet to announce a price. Amgen and Novartis had set the wholesale acquisition cost of their pioneering Aimovig at $6,900 for a year’s supply before raising it slightly this year; Lilly and Teva had followed suit with Emgality and Ajovy.

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

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Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

“We’re kind of like the old comfortable shoe,” Esperion’s chief commercial officer Mark Glickman remarked in an interview with Endpoints News ahead of the decision date. “It’s an oral product, once-daily and nontitratable — these are things that just resonate so true with patients and physicians and I think we’ve kind of forgotten about that.”

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

As it stands, the antibiotic market is cursed — it harbors the stink of multiple bankruptcies, a dearth of innovation, and is consequently barely whetting the voracious appetites of big pharma or venture capitalists. Enter artificial intelligence — the biopharma industry’s cure-all for the pesky process of making a therapeutic, including data mining, drug discovery, optimal drug delivery, and addressable patient population.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Today, the US Patent and Trademark Office ruled that Gilead was likely to lose the last two of those challenges as well. The USPTO ruled against Gilead on the first two patents earlier this month.

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Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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