#AACR17 roundup: Bris­tol-My­ers, Mer­ck KGaA and Pfiz­er in the spot­light, mark­ing progress with check­points

PHO­TO: © AACR/Todd Buchanan 2017

Julie Brah­mer, Johns Hop­kins
Bris­tol-My­ers IDs a sub­set of pa­tients who see a durable, 5-year re­sponse to Op­di­vo

Wash­ing­ton, DC — Now that the first wave of PD-1 check­point in­hibitors have been in use for awhile, we’re start­ing to see just how durable they can be for some pa­tients. In an up­date on Op­di­vo at AACR, Bris­tol-My­ers Squibb re­ports that they tracked a 5-year sur­vival rate of 16% for pa­tients with ad­vanced cas­es of non-small cell lung can­cer.

Based on his­tor­i­cal da­ta, Bris­tol-My­ers says that pa­tients in that cat­e­go­ry once could on­ly ex­pect a sur­vival rate of less than 5%.

“This is the first re­port of the long-term sur­vival rate in pa­tients with metasta­t­ic NSCLC treat­ed with an im­mune check­point in­hibitor. Our study re­sults show that for a small sub­set of pa­tients, im­munother­a­py can work for a very long time,” said Julie Brah­mer, as­so­ciate pro­fes­sor of on­col­o­gy at the Bloomberg~Kim­mel In­sti­tute for Can­cer Im­munother­a­py at Johns Hop­kins.

Fouad Namouni, Bris­tol-My­ers Squibb

What dis­tin­guish­es these pa­tients?

Bris­tol-My­ers Squibb’s Fouad Namouni, who runs the on­col­o­gy de­vel­op­ment group, tells me that they’re still work­ing on that, try­ing to un­der­stand the bio­mark­ers that could flag which pa­tients are most like­ly to get the most durable re­spons­es. One like­ly an­swer, he notes, is that the pa­tients with the most in­flam­ma­to­ry tu­mors, with the largest mu­ta­tion bur­den, could be ben­e­fit­ing dis­pro­por­tion­ate­ly.

More mu­ta­tions, he says, means that the tu­mors be­come “more vis­i­ble to the im­mune cell,” tar­get­ing them for de­struc­tion.

Pfiz­er, Mer­ck KGaA spruce up Baven­cio’s pro­file with a da­ta up­date
Howard Kauf­man, Rut­gers

Mer­ck KGaA and its part­ner Pfiz­er turned up at AACR over the week­end with some im­proved out­comes for their check­point drug avelum­ab, re­cent­ly ap­proved as Baven­cio for rare cas­es of Merkel cell car­ci­no­ma.

Ev­i­dence of a slight­ly amped up and more durable re­sponse will help these new ar­rivals on the check­point scene make quick progress as it works its way in­to an in­creas­ing­ly crowd­ed field. Start­ing with this rare form of skin can­cer, they now have 30 tri­als un­der­way in var­i­ous in­di­ca­tions, com­ing in be­hind Mer­ck, Bris­tol-My­ers and Roche.

As­traZeneca will be the next to ar­rive, as it leaps in­to a block­buster field with dur­val­um­ab. And be­hind As­traZeneca lie a whole new wave of check­points that are be­ing hur­ried along, as the pi­o­neers start a slew of com­bi­na­tion stud­ies — as our lat­est sto­ry on the IDO1 com­bos in­di­cate — to ad­vance their work.

The re­searchers for these two com­pa­nies re­port­ed that:

(A)fter longer fol­low-up, the num­ber of pa­tients to have a re­sponse in­creased to 29, for an over­all re­sponse rate of 33 per­cent af­ter a me­di­an of 16.4 months of fol­low-up. In ad­di­tion, the num­ber of pa­tients to have a com­plete re­sponse in­creased to 10 be­cause one of the par­tial re­spons­es had im­proved to a com­plete re­sponse, and an­oth­er pa­tient new­ly record­ed to have a re­sponse had a com­plete re­sponse.

At the time of da­ta cut­off, 21 of the re­spons­es were on­go­ing and the me­di­an du­ra­tion of re­sponse had not been reached. The re­searchers es­ti­mat­ed that 74 per­cent of pa­tients will have a re­sponse that lasts one year or longer.

Mer­ck KGaA sped through clin­i­cal tri­als in three-and-a-half years to get this first ap­proval, a mile­stone that Pfiz­er helped make hap­pen with a record $850 mil­lion up­front for its part­ner­ship arrange­ment with the Ger­man Mer­ck, which has gone well over a decade with­out a block­buster ad­di­tion from its R&D ops.

Howard Kauf­man, a sur­gi­cal on­col­o­gist at Rut­gers Can­cer In­sti­tute of New Jer­sey, not­ed:

The find­ings of long-term re­spons­es and well-tol­er­at­ed safe­ty pro­file sug­gest that avelum­ab could be an im­por­tant new agent for pa­tients with Merkel cell car­ci­no­ma who have failed pri­or chemother­a­py. Giv­en these re­sults, it will be in­ter­est­ing to de­ter­mine whether re­sponse rates could be in­creased by giv­ing avelum­ab pri­or to chemother­a­py or in com­bi­na­tion with oth­er treat­ments.

Op­di­vo, Yer­voy com­bo scores high­er sur­vival rate for melanoma, with worse ad­verse events

Bris­tol-My­ers, which has been work­ing on bol­ster­ing its case for a com­bi­na­tion of Op­di­vo and Yer­voy in treat­ing can­cer, al­so turned up at AACR with new da­ta that high­lights im­proved sur­vival rates for melanoma rates.

James Larkin, On­col­o­gist

On­col­o­gist James Larkin and col­leagues en­rolled 945 first-line pa­tients with ad­vanced melanoma and ran­dom­ly as­signed them in equal groups to nivolum­ab plus ip­il­i­mum­ab, nivolum­ab, or ip­il­i­mum­ab.

Af­ter a min­i­mum fol­low-up of 28 months, in­ves­ti­ga­tors re­port­ed, me­di­an over­all sur­vival among those pa­tients ran­dom­ly as­signed ip­il­i­mum­ab was 20 months. The me­di­an OS had not been reached for the nivolum­ab plus ip­il­i­mum­ab or the nivolum­ab plus place­bo arms.

A to­tal of 64% in the com­bo arm achieved two-year sur­vival, the high­est rate. The rate was 59% and 45% among those ran­dom­ly as­signed nivolum­ab plus place­bo and ip­il­i­mum­ab alone. But the com­bo arm al­so ex­pe­ri­enced worse ad­verse events.

Re­searchers added:

A sim­i­lar trend was seen for me­di­an du­ra­tion of re­sponse. Me­di­an du­ra­tion of re­sponse had not been reached in the nivolum­ab plus ip­il­i­mum­ab arm, while it was 31.1 months and 18.2 months for the nivolum­ab plus place­bo arm and ip­il­i­mum­ab alone arm, re­spec­tive­ly. In de­scrip­tive analy­ses, mean­ing the study was not pow­ered for this com­par­i­son, pa­tients ran­dom­ly as­signed nivolum­ab plus ip­il­i­mum­ab had a 12 per­cent low­er risk of death com­pared with those ran­dom­ly as­signed nivolum­ab plus place­bo.

“It is ex­cit­ing to see that ini­tial re­sults sug­gest that the nivolum­ab plus ip­il­i­mum­ab com­bi­na­tion pro­vides fa­vor­able sur­vival out­comes com­pared with ip­il­i­mum­ab alone,” said Larkin. “How­ev­er, the com­bi­na­tion al­so re­sults in a high­er rate of se­vere ad­verse events than nivolum­ab or ip­il­i­mum­ab alone, so it is im­por­tant to con­sid­er this when mak­ing treat­ment de­ci­sions for pa­tients.”

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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A low-pro­file biotech bests Re­gen­eron in high-pro­file patent suit

For nearly a decade now, the low-profile Cambridge biotech Kymab has been battling in US, UK, Japanese and Australian courts with the biotech behemoth Regeneron.

Regeneron has turned itself into a $70 billion company off of a platform of transgenically humanized mice they can use to make antibodies for anything from Ebola to colorectal cancer. The technology took decades and billions to build, 20 years from the company’s founding to the first approved drug. And the company guards and touts it zealously, breaking their production process down into various branded components — Velocimmune, Velocigene, Velocimouse and four other Velocis — and sometimes suing would-be copycats. In 2014, most notably, they sued two Pfizer-backed entities for patent infringement.

Credit: AP Images

Covid-19 roundup: BAR­DA sup­ports Op­er­a­tion Warp Speed with big $628M con­tract to ser­vice Amer­i­ca's vac­cine pro­duc­tion needs

Another BARDA contract designed to service America’s Covid-19 vaccine needs has been deployed.

The White House-led initiative designed to bankroll development to bring a vaccine to the American public by this fall — Operation Warp Speed — has via BARDA handed a meaty contract to the maker of an FDA-licensed anthrax vaccine to open up its manufacturing apparatus to shore up production of Covid-19 vaccines.

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Ken Frazier, AP Images

Why Mer­ck wait­ed, and what they now bring to the Covid-19 fight

Nicholas Kartsonis had been running clinical infectious disease research at Merck for almost 2 years when, in mid-January, he got a new assignment: searching the pharma giant’s vast libraries for something that could treat the novel coronavirus.

The outbreak was barely two weeks old when Kartsonis and a few dozen others got to work, first in small teams and then in a larger task force that sucked in more and more parts of the sprawling company as Covid-19 infected more and more of the globe. By late February, the group began formally searching for vaccine and antiviral candidates to license. Still, while other companies jumped out to announce their programs and, eventually and sometimes controversially, early glimpses at human data, Merck remained silent. They made only a brief announcement about a data collection partnership in April and mentioned vaguely a vaccine and antiviral search in their April 28 earnings call.

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