What's the hard cost of a piv­otal drug tri­al? A lot less than you might ex­pect

Of all the num­bers cit­ed by bio­phar­ma com­pa­nies to de­fend drug costs, $2.6 bil­lion — the es­ti­mat­ed cost of bring­ing a pre­scrip­tion drug to mar­ket — is by far the most pop­u­lar and res­o­nant. But per­haps less well-known was the Tufts re­searchers’ es­ti­mate of the av­er­age cost of Phase III tri­als, the most ex­pen­sive and ar­guably im­por­tant com­po­nent to scor­ing an OK: $255 mil­lion in 2014 dol­lars.

A new study is out to chal­lenge that.

Thomas Moore

Af­ter plug­ging de­tails about 101 new drugs ap­proved be­tween 2015 and 2017 in­to a clin­i­cal tri­al cost es­ti­ma­tor cre­at­ed by IQVIA, the au­thors con­clud­ed that the es­ti­mat­ed me­di­an piv­otal tri­al cost was $48 mil­lion, with an in­terquar­tile range of $20 mil­lion to $102 mil­lion. When you look at the 225 in­di­vid­ual tri­als, the me­di­an cost was $19 mil­lion (IQR $12 mil­lion to $33 mil­lion).

Per­haps more im­por­tant­ly, the re­search pa­per, pub­lished in the BMJ, of­fered a break­down of the fac­tors con­tribut­ing to costs.

Chief among them is the num­ber of pa­tients re­quired to es­tab­lish the treat­ment ef­fects — which var­ied wide­ly from just 4 to 8,442. The num­ber of tri­al clin­ic vis­its (2-166) al­so mat­tered, as did the type of treat­ment.

Tri­als for dis­eases where com­mer­cial drugs that have been proven to be ef­fec­tive typ­i­cal­ly re­quire more pa­tient en­roll­ment, they not­ed. Led by Thomas Moore, the sci­en­tists work at the In­sti­tute for Safe Med­ica­tion Prac­tices, a non­prof­it that mon­i­tors drug safe­ty. On av­er­age, the tri­als with an ac­tive con­trol group had 653 pa­tients, com­pared with 547 for place­bo-con­trolled stud­ies and 145 for un­con­trolled ones.

In a nod to the FDA’s in­creas­ing will­ing­ness to speed through new meds serv­ing pa­tients with few op­tions, the au­thors not­ed that 45 out of 101 drugs were ap­proved with a sin­gle tri­al — which trans­lat­ed to a low­er me­di­an cost of $28 mil­lion (IQR $13 mil­lion to $62 mil­lion). Those bur­dened with a repli­ca­tion re­quire­ment of two tri­als had an es­ti­mat­ed me­di­an cost of $45 mil­lion (IQR $28 mil­lion to $69 mil­lion).

While by no means rep­re­sen­ta­tive of the full pic­ture, the num­bers can un­der­cut phar­ma’s ar­gu­ments about the high cost of de­vel­op­ing drugs, since the piv­otal tri­als ac­count for a sig­nif­i­cant por­tion of the R&D spend­ing.

Ex­pect the usu­al de­bates and dis­cus­sions to fol­low. As the au­thors them­selves ad­mit, the num­bers are mere­ly their best es­ti­mates and not ac­tu­al costs. They al­so weren’t able to as­cer­tain all tri­al fea­tures, falling back on de­fault val­ues that could be in­ac­cu­rate. Since it fo­cused on CRO costs, it ex­clud­ed spon­sor costs for tri­al de­sign, mon­i­tor­ing or pro­vid­ing the drug it­self.

Drug de­vel­op­ers might al­so add that in pric­ing new drugs, they fac­tor in failed projects — vir­tu­al­ly al­ways out­num­ber­ing the suc­cess­ful ones — and cost of cap­i­tal.

Still, the es­ti­mat­ed costs are mod­est for es­tab­lish­ing what amounts to the path guid­ing a drug to thou­sands or mil­lions of fu­ture pa­tients. Count­ing by per pa­tient en­rolled, the cost would just be $41,413. From the BMJ pa­per:

Note that these costs-per-pa­tient for these tri­als are some­times sim­i­lar to what phar­ma­ceu­ti­cal com­pa­nies charge for these same drugs to treat a sin­gle pa­tient or a hand­ful of pa­tients af­ter mar­ket­ing ap­proval.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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In­cyte’s PD-(L)1 in­hibitor head­ed for an ODAC show­down next month

The FDA’s Oncologic Drugs Advisory Committee will spend a half day on June 24 reviewing Incyte’s PD-(L)1 inhibitor retifanlimab as a treatment for locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) for those who have progressed on or who are intolerant of platinum-based chemotherapy.

The eighth PD-(L)1 entrant in January nabbed a priority review and an orphan designation from the FDA, which sets the agency’s final decision date as July 25.