Thursday, February 6, 2014

We Love The Audacity! Merck Is Making Astoundingly Big Bets On Lambrolizumab -- MK-3475

I think some assume we are eternal Merck scolds, here (that's the Royal "we" by the way). We are not. We were Schering-Plough critics. But it has almost bodily vanished into the mists of eternity. We are, and remain, more than occassionally -- just a little skepical of big pharma, generally. But now, I am in recovery -- from these afflictions -- on all fronts. Truly. I am. Heh.

Exhibit A? I am flat out jazzed, for Whitehouse Station! More precisely, I am just frothy with anticipation -- about the future prospects of MK-3475, or lambrolizumab, if you prefer. It is a stunningly new way of fighting cancer. It does so essentially by removing the natural "brake" built in to our own immune systems (see graphic at right; it was derived from this fine article). MK-3475, it is thought, blocks a specific T-Cell "down regulator" -- and that allows our bodies' immune system to fire machine-gun fashion, at specific tumor cells. Rather than cock and reload and aim and fire -- this (it is thought) converts the bodies' own anti-cancer weapons into a "Gatling gun", on the fly. That is, it amps up our own counter-attacks -- and leaves healthy cells unpreturbed (or so the early data might suggest). [Now, to be fair, Bristol Myers Squibb has a prior in time anti-PD-1 candidate in its pipe, one called nivolumab, and it may actually beat Merck to market -- clear FDA review -- as to at least some oncology indications.] Even so, there will be "plenty of pie," to go around -- if this approach works as well as it would seem it might. The oncology markets currently targeted by the two companies, independently, rake in perhaps $45 billion per year, in the aggregate -- with what appear to be significantly less effective on-market drugs. [Backgrounder here.]

Of course, as with any biotech approach, a million things could still go wrong -- for example, the longer term effect might be that the patient's immune system goes haywire, generally, over time -- and starts attacking healthy cells, indiscriminately. That's not likely (given graphic at right), but it is at leat remotely possible. The reply would be that in end-stage cancer patients (where the bio-tech will be initially deployed), these patients are likely to die within six months, in any event. And if the treatment works, they may gain a minimum of two to five more good years.

That sort of survival benefit will compel the world's various versions of reimbursement machinery to pay a perhaps quite hefty premium for nivolumab and/or lambrolizumab. But let's not get too far ahead of the story. The story right now is a horse race -- and in a nice piece by the U.K. based PharmaTimes, we are treated to some of the detail, about Merck's three additional entries:
. . . .With Pfizer, Merck will assess in Phase I/II clinical studies the safety and efficacy of MK-3475 in combination with the former's small molecule kinase inhibitor Inlyta (axitinib) in patients with renal cell carcinoma, and separately MK-3475 plus PF-05082566 (PF-2566), an investigational immuno-oncology agent that targets the human 4-1BB receptor, in multiple cancer types.

Incyte and Merck will collaborate on a randomised, double-blind placebo controlled Phase I/II study to evaluate the safety and efficacy of a regimen combining MK-3475 with Incyte’s investigational immunotherapy agent INCB24360 in patients with previously-treated metastatic and recurrent NSCLC, among other advanced or metastatic cancers.

Amgen and Merck will look at MK-3475 in combination with Amgen’s investigational oncolytic immunotherapy talimogene laherparepvec in a Phase I/II study in patients with previously untreated advanced melanoma.

MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy which is designed to restore the natural ability of the immune system to recognise and target cancer cells, and analysts are expecting the drug to make peak sales of at least $2 billion if it makes it to market. . . .

To be sure, this spend in the near term, at Merck, is not small. The three above, plus the two previously-announced, likely place the quarterly spend on the MK-3475 clinical trials at $1 billion. Or about $4 billion on the year 2014. If Merck hits solid doubles in four or five of these, though -- that $2 billion a year in projected revenue might be closer to $6 or $8 billion, a year. Overall most analysts still figure BMS's nivolumab will reach between $6 and $12 billion. A year. And (if approved at FDA) it is not likely that the pie will shrink much, when Merck enters. There is just that much pent up demand for a truly effective, time-of-survival enhancing approach -- for cancer patients in the renal, melanoma and lung (and later -- in the bone and blood) cancer arenas. Now we wait for the end of May/first of June, 2014, and ASCO in Chicago -- when the next big data sets, on anti-PD-1, will be out.


Anonymous said...

I'm not ready to let go...I don't think I can do this right now. I'm sorry.

Anonymous said...

Anonymous said... @ 9:15 AM

What concrete info do you have on Nivolumab? What timeframe should we see the approval in? There were rumours BMS was delaying his anti-pd1....

-- bijz[redacted characters]

[Editor's Note -- removed your full email address. You don't want that out in the open, here, Anon. Trust me.

Namaste -- Condor

Condor said...

Thanks for stopping in, Anon.! --

You clearly know your stuff. SO let me pay you the compliment of speaking in fairly sophisticated, shorthand prose. A lot of the answer turns on nuances of SEC rules and releases and cases -- which would take a chapter to lay out for a true neophyte. . . but that isn't you. So, here goes:

My most recent, on the record pieces -- with concrete nivolumab updates -- are here, here and here.

Through my own research, and scientific journal readings, attending scientific conferences (and buying the right people drinks!), chats with academic contacts, and other cocktail conversation -- at public company biotech/pharma functions. . .

I have peiced together much, much more. But I won't trade on it. Ever.

The trick -- and frankly SEC problem, here -- is that almost anything on nivolumab that isn't already known to be true and in the public domain (from BMS or a similarly credible source) -- may be material to the securities trading prices of Bristol Myers Squibb common stock.

And I'll never endanger any off-the-record conversant, nor ever ever encourage (nor knowingly allow anyone I talk with) to execute a securities trade, on anything I received from someone who owed anyone else a duty of confidentiality -- as to the information.

As to Merck, that's easy. I only report on -- and analyze, here -- what is already public. My own take on it is no different than any Wall Street analyst. It is just one guy's opinion. Perfectly lawful, and appropriate. [I could even trade on it, though I almost never will.]

As to BMS, I'll rarely ever really know whether what someone has shared with me is simple idle speculation, or based on hard inside information.

And as I say -- very much like a journalist in this respect -- my sources are forever sacrosanct.

So -- all I can tell you, here -- since I do not know you, and know you to be worthy of trust -- is the BMS is far more conservative than Whitehouse Station has been of late, in making predictions about not yet FDA approved biotech cancer candidates, nivolumab chief among them. [And even so, Merck is not officially guessing at an approval date for MK-3475.]

Whitehouse Station is likely a little more cavalier, here because almost no MK-3475 revenue is baked into today's NYSE price. And it is a smaller piece of Merck's pie than Nivolumab will be to BMS, each upon approval. So, no one can really complain if Merck finishes more than six months behind BMS -- if Merck is. . . wrong.

And the truth is, I still believe, based on all I know, that BMS will -- as to the largest/deepest markets, i.e., label indications, here -- beat Merck by six months or more, inside the US (get FDA approval first).

But I could be wrong. And of course, oncologists can always write off-label, if Merck gets a narrow label, at first.

Then the trick will be getting insurers, Medicare/Medicaid and the nascent ACA exchanges to fully reimburse the perhaps $120,000 per patient dosing price -- for either MK-3475, or nivolumab.

More on that, another day. . . .

Thank you so much for the questions!

Do stop back!


Parker Alex said...

The designation will help in expediting the development and review of drugs for serious or life-threatening conditions.

This is an important milestone for Bristol Myers Squibb as they continue the strategic focus on the development of innovative medicines to address areas of high unmet medical need, where potential expedited review can make a critical difference for patients.

Condor said...

Thanks for stopping by, Alex Parker --

I do think nivolumab will be a winner for BMS. TO be lcear, though, the breakthrough designation has been granted to Merck, on MK-3475 (now called pembrolizumab, formerly playfully named lambrolizumab).

That said, I still think the lead belongs to BMS, here. It is theirs to lose.

Do stop back, and. . . as ever. . .


Condor said...

Your link notes that FDA granted BMS breakthrough status on annext gen Hep-C treatment, and nivolumab is an oncology candidate.

Even so, the HCV candidate for BMS is a solid one. And I think it holds the lead over the next gen candidate Merck has in the pipe, as well. So, in both candidates' cases, BMS is ahead -- by my lights.

Do stop back by. . .