#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.”

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

Paul Hudson (Getty Images)

Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

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SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

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No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

In­cyte keeps rolling on top­i­cal cream for JAK in­hibitor, pass­ing two PhI­II tests in vi­tili­go

As Incyte prepares to potentially hit the market with a topical formulation of its cash cow ruxolitinib in atopic dermatitis, the Wilmington, DE-based company is beefing up its data package for another indication: vitiligo.

Incyte released Phase III results from two of its clinical vitiligo programs Monday morning, saying both studies met their primary endpoints of patients achieving at least 75% improvement from baseline in repigmentation of the face. The data will likely lead Incyte to ask for approval in both the US and Europe for those older than 12 before the end of the year.

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.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

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Days ahead of Am­gen split, Cy­to­ki­net­ics reads out post-hoc da­ta sug­gest­ing heart drug works bet­ter in sick­er pa­tients — but can the CEO win over skep­tics?

While Cytokinetics’ heart drug technically met its primary endpoint back in November, it missed a key secondary endpoint — reduction in cardiovascular death — which eventually cost the company two partnerships. Now the team is back with data suggesting the drug works better in sicker patients, and it’s planning a trip to the FDA.

In a post-hoc analysis, which can be a very difficult sale at the FDA, Cytokinetics separated patients from the Phase III GALACTIC-HF study into four quartiles based on ejection fraction, a measurement of how well the left ventricle pumps blood with each heartbeat. Patients in the lower two quartiles — those with an EF of 22% or lower, and between 29% to 32% — saw a 15% and 17% relative risk reduction of heart failure events and cardiovascular death combined, Cytokinetics reported at ACC. No difference was seen in the upper two quartiles.