Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

De­spite a head start, when Bris­tol-My­ers Squibb and its pi­o­neer­ing check­point in­hibitor Op­di­vo suf­fered a key lung can­cer set­back in 2016, they found them­selves rel­e­gat­ed to the back­seat as Mer­ck’s Keytru­da seized the wheel on the road to im­munother­a­py star­dom. Bris­tol-My­ers has since suf­fered blow af­ter blow in its quest to take a big slice of the lu­cra­tive mar­ket, pep­pered with some small suc­cess­es. On Tues­day, the New Jer­sey drug­mak­er tout­ed pos­i­tive da­ta from a Phase III open-la­bel study in a bid to carve it­self a piece of the front­line lung can­cer mar­ket.

The study, dubbed Check­Mate -9LA, test­ed Bris­tol-My­ers’ Op­di­vo in com­bi­na­tion with its CT­LA-4 Yer­voy in ad­di­tion to chemother­a­py (two cy­cles) ver­sus chemother­a­py alone (up to four cy­cles fol­lowed by op­tion­al peme­trexed main­te­nance ther­a­py if el­i­gi­ble) as a first-line treat­ment in pa­tients with ad­vanced non-small cell lung can­cer (NSCLC) re­gard­less of PD-L1 ex­pres­sion.

The PD-L1 drug met the main tri­al goal of su­pe­ri­or over­all sur­vival at a pre­spec­i­fied in­ter­im analy­sis, the com­pa­ny said, adding that de­tailed da­ta will be pre­sent­ed at a fu­ture med­ical con­fer­ence. The com­pa­ny’s shares $BMY rose more than 5% to $55.94 in Tues­day pre­mar­ket trad­ing.

Sec­ondary end­points in­clud­ed pro­gres­sion-free sur­vival, over­all re­sponse rate, and ef­fi­ca­cy mea­sures ac­cord­ing to bio­mark­ers.

In Jan­u­ary, the com­pa­ny re­scind­ed its ap­pli­ca­tion to mar­ket the Op­di­vo/Yer­voy com­bo in front­line NSCLC cas­es with high tu­mor mu­ta­tion­al bur­den (TMB), af­ter dis­cus­sions with the agency sug­gest­ed they need­ed more da­ta to re­in­force the con­nec­tion be­tween TMB and PD-L1.

The ap­pli­ca­tion was based on the Check­Mate-227 study, in which re­searchers said they had ob­served a “high­ly” sig­nif­i­cant pro­gres­sion-free sur­vival rate in pa­tients with high TMB, re­gard­less of PD-L1 ex­pres­sion. The high TMB group ac­counts for 45% of all front­line pa­tients, the com­pa­ny es­ti­mat­ed at the time. Bris­tol-My­ers had re­designed the study to fo­cus on TMB af­ter stum­bling on a piv­otal tri­al that in­volved a broad­er pa­tient pop­u­la­tion.

Over­all sur­vival da­ta, pre­sent­ed months lat­er, showed that the haz­ard ra­tio in pa­tients get­ting the Op­di­vo/Yer­voy com­bo was com­pa­ra­ble whether they were high or low TMB pa­tients. How­ev­er, the me­di­an over­all sur­vival in pa­tients with high TMB was 23.03 months on the Op­di­vo/Yer­voy arm, ver­sus 16.72 months in the chemother­a­py group. In the low TMB group, the me­di­an OS was 16.20 months and was 12.42 months on the com­bi­na­tion and chemother­a­py arms, re­spec­tive­ly.

The re­sults of Check­Mate-227 sug­gest­ed that Yer­voy has ac­tiv­i­ty in lung can­cer when com­bined with Op­di­vo — but the da­ta sug­gest that pa­tients have to wait for some pe­ri­od of time for the ben­e­fit to man­i­fest, Wolfe Re­search’s Tim An­der­son wrote in a note.

“Chemother­a­py, when giv­en to lung can­cer pa­tients, of­ten shows a fast ini­tial re­sponse, but one that lacks dura­bil­i­ty.  But by com­bin­ing chemother­a­py+Op­di­vo+Yer­voy, BMY may have (fi­nal­ly) found a cock­tail of drugs that de­liv­ers both near- and longer-term ben­e­fit, lead­ing to an ear­ly re­sponse and im­proved long-term sur­vival.”

How­ev­er, An­der­son was cau­tious about the cock­tail’s safe­ty pro­file in Check­Mate -9LA.

“Op­di­vo+Yer­voy by it­self shows tox­i­c­i­ty and adding chemother­a­py in­to the mix will on­ly in­crease this,” he said.  “The com­mer­cial val­ue of CM-9LA will, there­fore, de­pend on the bal­ance be­tween the clin­i­cal ben­e­fit and the tox­i­c­i­ty.  It will on­ly be once full re­sults are pre­sent­ed that this risk:ben­e­fit as­sess­ment will be pos­si­ble.  Ad­di­tion­al­ly, adding a third drug in­to the mix al­so rais­es the cost of ther­a­py some­what.”

Mean­while, the com­pa­ny’s hunt for adop­tion in small cell lung can­cer (SCLC) mar­ket has al­so been punc­tu­at­ed with fail­ure.

Last year saw an Op­di­vo/Yer­voy com­bo miss the pri­ma­ry end­point for over­all sur­vival in the Check­Mate-451 study, where the Bris­tol-My­ers drugs were be­ing eval­u­at­ed as a main­te­nance ther­a­py for SCLC, fol­low­ing an ini­tial round of chemother­a­py. The re­sults came just over a month af­ter the drug­mak­er un­veiled an Op­di­vo flop in the Check­Mate-331 study, which test­ed the im­munother­a­py against the sec­ond-line small cell lung can­cer stan­dard-of-care.

Still, over the years, Op­di­vo has seen some lung can­cer suc­cess — in­clud­ing the ap­proval of the drug in squa­mous NSCLC pa­tients whose can­cer has pro­gressed de­spite plat­inum-based chemother­a­py as well as pa­tients with metasta­t­ic SCLC pa­tients, whose can­cer has pro­gressed af­ter plat­inum-based chemother­a­py and at least one oth­er line of ther­a­py.

The re­sults of Check­Mate -9LA could have an im­pact on As­traZeneca, which is run­ning the PO­SEI­DON tri­al, An­der­son added.

The tri­al is struc­tural­ly sim­i­lar to CM-9LA but with one key dif­fer­ence — in­stead of on­ly giv­ing a short course of chemother­a­py in ad­di­tion to its own check­point in­hibitor Imfinzi  and CT­LA-4 treme­li­mum­ab, it gives chemother­a­py con­tin­u­ous­ly, he said.

“This may or may not be a good thing – it can be pre­dict­ed that more chemother­a­py like­ly yields more tox­i­c­i­ty, but will it yield more ben­e­fit?  Fur­ther­more, AZN’s an­ti-CT­LA4 ther­a­py (treme­li­mum­ab) has yet to show it works in any tu­mor type (by con­trast, BMY’s Yer­voy is al­ready ap­proved in dif­fer­ent set­tings) po­ten­tial­ly re­flec­tive of the fact that it has slight­ly dif­fer­ent prop­er­ties ver­sus Yer­voy.”

Op­di­vo, which is al­so ap­proved for use in a host of oth­er can­cers, gen­er­at­ed about $3.6 bil­lion in the first half of this year. By 2025, Op­di­vo is set to be the fourth best-sell­ing drug in the world with an­nu­al sales fore­cast­ed to hit $12 bil­lion. King Keytru­da, how­ev­er, is ex­pect­ed to take top spot and rake in more than $22 bil­lion, ac­cord­ing to Glob­al­Da­ta cal­cu­la­tions.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.

Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.

Genen­tech plots $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Genentech has committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Roche’s big South San Francisco hub will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.