Saturday, August 6, 2016

A Recap -- FDA Approved Indications For Keytruda®: As Of August 6, 2016


Kenilworth got some important additional good news late yesterday, just two hours before the celebration of the opening of the Summer Olympics got underway, with a Samba party, and segments on some of the planet's more vexing problems -- in Rio. And so, instead of yet another graphic with the Keytruda® wordmark, I'll run a picture of the first refugee squad to compete in a modern Olympics, at right. It reminds us all that despite what Mr. Trump says, we are all citizens of the same planet. It reminds us, as Maya Angelou so mellifluously intones "we are more alike, my friends, than we are unalike." And we are "each our brother's and our sisters' keepers," in the Gospel of Matthew 25: 31-45.

In a not entirely unrelated vein (stretching all the life we can, from this time on the planet), then -- we will note that Merck's immuno oncology agent, pembrolizumab, won yet another new indication -- after the NYSE closed last evening. This time it was for second line recurrent or metastatic head and neck squamous cell carcinoma, during or after chemo. This is decidedly good news. And it widens Merck's footprint here, nicely.

Having said all that, I've set out below the cancers for which pembrolizumab already is approved -- and we all may accept that it is being used "off-label" in several others. Just as BMS's nivolumab is being used. So, as you look at the below, remember that perhaps 15 to 20 per cent of all sales revenue, for both BMS and Merck in this space is "off-label".

In that context, we may more readily accept that nivolumab, or Opdivo® as it is branded, will continue to outsell pembrolizumab about two-to-one, as it is approved for several more indications, and being used by oncologists, in more off label. The fact that Checkmate 026 missed its end-point primarily means that BMS will not generate five to eight times Merck's sales, in 2017-18 (and I'd argue that the pre-Friday NYSE price never gave BMS full credit for those sales that had not yet been booked). So again, I think the 15 per cent downturn in BMS's NYSE price yesterday was at least a bit of Chicken Little. I'd look for it to recover most of that, in the coming weeks, as cooler heads prevail. Here's a bit from Merck's latest press release:

. . . .Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks.

Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy, at a dose of 2 mg/kg every three weeks. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab). This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy at a fixed dose of 200 mg every three weeks. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. . . .


As ever, I think this is all good for cancer patients everywhere generally, and for Merck's fortunes, particularly -- but it is not too terribly negative for BMS, either. One's gain need not always be another's loss. Opdivo is still a first in class best in class agent. Off now, to a secluded lake in the north woods, for some tent and kayak time. . . back Sunday evening -- smile. Be one anothers' keepers, one and and all -- "whatsoever you do for the least of my children. . . ."

6 comments:

Anonymous said...

More alike, than not alike... smile -- mornin'...

Anonymous said...

I usually am in full agreement with you but not this time. This is a big deal, bigger than you make us believe. Underlying this story is the fact that BMS consistently has de-emphasized the value of a biomarker(s), even an imperfect one like PD-L1, to guide patient selection, thereby ignoring the science that should drive decision making. In this case BMS paid a steep price. It looks like Merck on the other hand stuck with the science and the outcome apparently is very different.

Although BMS will likely recover, it highlights what happens if one moves away from core principles - in this case scientific rigor

Condor said...

Well-put.

I do still think BMS will be fine with Opdivo. But I agree about reaching for too much, from the science perspective -- a la Icarus -- flying too close to the Sun...

Namaste

Anonymous said...

Agree with Anon - this is a bigger deal than not and post-ESMO the docs are starting to discuss that Opdivo and Keytruda are more non-alike than alike.

Condor said...

I do hear you -- I just think testing for all patients is the new normal in NSCLC... for all three (including off-label -- for Tecentriq).

So with three potential therapies... it will be a reimbursement question.

We shall see.

Namaste -- do stop back.

Anonymous said...

I agree that it comes down to a question of reimbursement, as you note.