Bris­tol-My­ers with­draws Op­di­vo/Yer­voy lung can­cer EU ap­pli­ca­tion — but oth­ers are in­com­ing

Ear­ly in 2019, Bris­tol-My­ers Squibb re­scind­ed an FDA ap­pli­ca­tion to mar­ket its check­point in­hibitor Op­di­vo in com­bi­na­tion with its CT­LA-4 ther­a­py Yer­voy for front­line use in pa­tients with the most com­mon form of lung can­cer. One year lat­er — the com­pa­ny is tak­ing the same step with the Eu­ro­pean reg­u­la­tor.

De­spite a head start, when Bris­tol-My­ers’ 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. The drug­mak­er has since suf­fered a se­ries of blows in its quest to take a big slice of the lu­cra­tive mar­ket, pep­pered with some suc­cess­es.

This Op­di­vo/Yer­voy com­bo was meant to claw back some of that lost ground. Orig­i­nal­ly filed in 2018, the EU ap­pli­ca­tion was de­signed to al­low the use of the Op­di­vo/Yer­voy as a first-line reg­i­men in pa­tients with non-small cell lung can­cer (NSCLC) with high tu­mor mu­ta­tion­al bur­den (TMB) on the ba­sis of the Check­Mate-227 study.

In one arm of the tri­al, which com­pared the com­bo to chemother­a­py, 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, post­ed 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.

Since the OS da­ta came lat­er, the EU ap­pli­ca­tion was amend­ed ac­cord­ing­ly. A full as­sess­ment of the ap­pli­ca­tion by the EU reg­u­la­tor was not pos­si­ble fol­low­ing mul­ti­ple pro­to­col changes the com­pa­ny made, Bris­tol-My­ers’ said, cit­ing its re­sponse from the EU agency.

The com­pa­ny — which with­drew a sim­i­lar US ap­pli­ca­tion in Jan­u­ary 2019 af­ter it was un­able to con­vince the FDA of the con­nec­tion be­tween TMB and PD-L1 — has no plans to re­file this ap­pli­ca­tion in the EU, it said on Fri­day.

In­stead, Bris­tol-My­ers has tak­en a slight­ly dif­fer­ent ap­proach. Last month, the FDA grant­ed the com­pa­ny’s ap­pli­ca­tion for the Op­di­vo/Yer­voy com­bo for the first-line treat­ment of pa­tients with metasta­t­ic or re­cur­rent NSCLC with no EGFR or ALK ge­nom­ic tu­mor aber­ra­tions pri­or­i­ty re­view, on the ba­sis of the same Check­Mate-227 study.

In ad­di­tion, Bris­tol-My­ers plans to file ap­pli­ca­tions across the At­lantic fol­low­ing the re­sults of a Phase III open-la­bel study — Check­Mate -9LA — which eval­u­at­ed the im­pact of Op­di­vo/Yer­voy ad­min­is­tered con­comi­tant­ly with a lim­it­ed course of chemother­a­py for the first-line treat­ment of NSCLC.

Lung can­cer is the most lu­cra­tive on­col­o­gy mar­ket — and as such, check­point in­hibitors of all hues have been scram­bling to gain ground in the field. For now, Mer­ck’s Keytru­da re­mains way in front. Ac­cord­ing to 2024 pro­jec­tions com­piled by Cowen an­a­lysts, Op­di­vo is ex­pect­ed to gen­er­ate a meaty $12.4 bil­lion that year, while king Keytru­da is ex­pect­ed to reap a hefty $20.6 bil­lion.

Bris­tol-My­ers hunt for adop­tion in the small­er small cell lung can­cer (SCLC) mar­ket has al­so been punc­tu­at­ed with fail­ure. 2018 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 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 SCLC 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, whose can­cer has pro­gressed af­ter plat­inum-based chemother­a­py and at least one oth­er line of ther­a­py.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Christian Itin, Autolus CEO (UKBIO19)

Au­to­lus tips its hand, bags $220M as CAR-T show­down with Gilead looms

The first batch of pivotal data on Autolus Therapeutics’ CAR-T is in, and execs are ready to plot a path to market.

With an overall remission rate of 70% at the interim analysis featuring 50 patients, the results set the stage for a BLA filing by the end of 2023, said CEO Christian Itin.

Perhaps more importantly — given that Autolus’ drug, obe-cel, is going after an indication that Gilead’s Tecartus is already approved for — the biotech highlighted “encouraging safety data” in the trial, with a low percentage of patients experiencing severe immune responses.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

Endpoints Premium

Premium subscription required

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

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

Scoop: Gilead ter­mi­nates ear­ly-stage FLT3 tri­al in sol­id tu­mors

Gilead chopped a Phase Ib dose escalation study in recent days, with an update to the federal trials database saying the premature termination followed an “internal safety assessment.”

The IV-administered FLT3 agonist, dubbed GS-3583, was being tested as a monotherapy in 13 patients with advanced solid tumors. The goal of the trial was to find out what dose to test in a Phase II, or maximum tolerated dose.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

As­traZeneca’s Su­san Gal­braith high­lights twin wins for the can­cer drug pipeline at SABCS, as oral SERD ex­cels

It’s a good time to be the head of R&D for oncology at AstraZeneca. And no one gets that quite like Susan Galbraith.

Today, Galbraith is at the San Antonio Breast Cancer Symposium, highlighting the data on two key drugs in the cancer pipeline: mid-stage results for its oral SERD camizestrant among patients after one line of therapy, and the AKT drug capivasertib, wrapping the Phase III. Both fall neatly into the range of successes, beating out fulvestrant in hormone receptor-positive, HER2-negative breast cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,300+ biopharma pros reading Endpoints daily — and it's free.