So it is highly likely that Merck will win the approval after priority review is complete, in January at FDA. In any event, here's the latest from the wires -- but do go read it all:
. . .Merck’s KEYNOTE-A18 clinical trial showed that Keytruda plus chemoradiotherapy outperformed concurrent chemoradiotherapy. The endpoint offered a statistically significant improvement in progression-free survival.
The FDA circled January 20, 2024, as the target action date for a decision on the priority review. Keytruda is already approved in the U.S. in combination with chemotherapy and as a mono-therapy, for patients with cervical cancer whose tumors harbor the PD-L1 biomarker. . . .
All good news, to be sure.
And now, if I might editorialize a bit -- it is true that all these clinical trials are wildly expensive -- and the ten year development arc for pembrolizumab likely cost close to $2 billion if fairly valued in today's dollars. All that is true.
And Keytruda is one of dozens of projects like it at Merck -- though in fairness it is the largest, in dollars spent.
Having said that, Keytruda is also the most successful therapy in Merck's long history -- now generating almost $22 billion a year in revenue, globally -- and still growing at over 15 per cent a year, on the back of great study results in new arenas, like the above. It will enjoy exclusivity at the patent office until well after 2035 (with even moderately aggressive additional filings).
It is not hyperbole to call that. . . a life or death choice. And that is simply. . . wrong. And Mr. Davis well-knows it.
He should voluntarily dismiss his silly strike suit -- and sit down to negotiate sensible prices on these old (long paid for) drugs, with HHS and CMS. Out.
नमस्ते
6 comments:
I think you're off by a factor of 10-20x on the total development cost for Keytruda.
Thanks Anon. -- if you have figures as endorsed by Rahway, I'd love to see them.
My understanding is that it was -- far and away -- the most expensive set of studies involving one drug -- in Merck's history.
They must have about 45 clinical trials running, on various cancers, still.
That said, those are crimes of opportunity, right? I mean, once it got first approved in one cancer -- in 2016, if memory serves -- the oncologists could all use it off-label on all other cancers.
But to be sure, having a clinical trial in melanoma, for example, that was world-beating meant that former Pres. Jimmy Carter could be given it with confidence. And he is still doing well, seven years later (at least on the oncology front -- his overall decline looks to be one related to growing ever nearer the 100 year mark).
My point is that larding on the top, all those clinical trials that juice up sales... hardly seems fair.
Yes, I've seen that Merck thinks it will have spent nearly $80 billion, all in when all the trials have reported out.
But to get the first, original approval (the go / no go, at FDA) was closer to $4 billion, tops.
Please share if you have credible information that is public domain, to the contrary.
In any event, thanks for the fact checking! I think we are talking differing definitions, here.
Namaste. . . .
Off-label use rarely gets payer reimbursement, generally just indication specific regulatory approvals with appropriate differentiation over standard of care do. On that item you're wholly wrong. If you want to get paid by a government or an insurer to use Keytruda in an indication, you need the regulatory label, and that generally requires you to run the Ph3 study.
I don't know off-hand of a an accurate public number for total Keytruda investment by Merck. I can point you to clinicaltrials.gov where the numbering for Keytruda protocols passed 999 several years ago (I hope you noted the prefix 'A' on the protocol number on this specific post as emphasis to that point)
I can do some back of the envelope math, clinicaltrials.gov lists 186 Ph3 Keytruda studies as active or complete as of my searching today. Benchmarking a conservative cost of $100MM per Ph3 study, that's just over $18B. That doesn't factor the other hundreds of Ph1 and 2 studies which are ongoing or complete, or the ones which Merck hasn't started yet.
Your point about the frivolity of Merck's suit against HHS remains extremely valid, and no amount of research cost justifies Merck's flawed legal position, but diminishing the amount of money spent on turning Keytruda into the financial juggernaut that it is doesn't do your argument any favors.
Thanks Anon. -- these are all very valid points, but having been the lawyer on several old school oncology agent clinical trials. . . very few of the studies need an "n" large enough to support your $100 million per trial guess.
Those are the exception rather than the rule. And given that progression free survival in oncology is the golden ticket to FDA accelerated approval (as it ought to be!), getting to statistical significance with a wonder drug like Keytruda is simply a matter of time. Usually under two years.
Compare that to the (mostly failed) cholesterol studies on Vytorin, where it might take 65,000 patients over five years duration. That was a $100 million failure, obviously.
But my point remains: these later studies simply super-charge the annual sales in new tumor arenas.
And you neglect to mention that -- as has always been true -- the wealthiest 2% in every nation will get Keytruda off label, and pay cash without batting an eye. It is the ticket to many months or years (if not decades) of meaningful symptom. . . free life.
I really appreciate the point/counterpoint. . . and don't mean to seem snippy.
We certainly agree that refusing to even talk price to perhaps its largest customer base (all the federal payors, broadly grouped). . . is a show of rather disgusting hubris, industry wide.
Pharma as an industry is among the most profitable group of businesses on Earth. It is pure sophistry to argue that having hold a line on price will kill innovation.
The vast profit incentive for innovative drugs and biologics will draw them back -- even if Januvia is required to stop raising prices to a level beneath the US inflation rate each year. And at over $65,000 per year, for a Keytruda regimen, per patient. . . Merck will never, ever lose money on that franchise. To borrow a catch-phrase:
"If you build it, they WILL come. . . ."
In fact -- the entire pharma industry. . . already has, in fine "Field of Dreams" style.
Cheers -- and I greatly appreciate the differing perspectives, here!
G'night.
Wholly agreed that the profit motive for drug development doesn't disappear under US pricing pressure and any argument to the contrary is posturing. Just noting that the regulatory state requires the level of investment Merck has chased with Keytruda, profit mining the same, there's been no other way to regularly reach most patients other than to continue to run Ph3 studies in more and more indications.
As far as your view on the cost, duration, and size of oncology trials, I'm sorry to say, your view is...dated.
https://clinicaltrials.gov/study/NCT04221945?term=3475%20A18&rank=1
Review the study details for Keynote A18, your topic for this post, patient n= ~980 with treatment and follow-up duration of 3 years. PFS/OS outcomes regularly take more than 2 years.
You also posted recently about the miss in Head and Neck, that study is here:
https://clinicaltrials.gov/study/NCT05523323?term=leap-010&rank=1
150 patients with an originally estimated 6 year follow-up period. I'll note it succeeded within 2 years on PFS but failed on OS, which means this won't get a label.
You also recently posted about Keytruda's promise combining with Moderna's personalized cancer vaccine. That Ph3 is here:
https://clinicaltrials.gov/study/NCT05933577?cond=melanoma&term=Adjuvant%20&intr=Keytruda&rank=3
again, >1000 patients and half a decade of expected patient follow-up given the OS bar it likely needs to clear.
Ironically, with the profound success of Keytruda, the bar for approvals was raised by both the marketplace and by the FDA several years ago. Gone are the days of a $50MM oncology pivotal trial.
Well... even a 1,000 person trial is not... a 65,000 person trial.
I am sure (having done at least some, myself!) that creative accounting, on cost allocation might be tortured to allow Merck to absorb the bulk of the cost of new corporate HQ as "clinical trials" costs-related... but that doesn't make it. . . true -- that each 1,000 person trial actually costs... even $20 million. It just doesn't -- if the follow up runs less than seven years.
A 65,000 person trial (as I mentioned) costs about $100 million. The daunting task of tracking that many over a half-decade or more. . . is a real, out of pocket expense.
Not so much, when cancer patients are being seen almost weekly at a large university teaching hospital, and closely monitored by their participating oncologists.
Compared to the cholesterol management studies -- with 65,000 blue collar working stiffs who only are compliant with the meds sporadically, and may miss even an annual physical date from time to time. You need an army of sleuths, to figure out what 65,000 otherwise pretty healthy middle aged people are up to. Or, not up to.
But I will let it go, here and now -- then.
We will (I suppose) agree to disagree: I think Merck generally overstates what it costs to develop drugs. But so do almost all larger multinational pharma concerns.
We agree on the important part -- that's that drugs in the US have been priced well beyond any actual measure of the cost to make them.
Cheers!
And, thanks again -- for refining my thinking!
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