Skep­tics pounce af­ter Bris­tol-My­ers scores an ear­ly hit on Op­di­vo-Yer­voy com­bo for lung can­cer

Bris­tol-My­ers Squibb’s close­ly watched study dubbed Check­mate-227 hit ear­ly, with re­searchers tout­ing a suc­cess for their com­bi­na­tion of Op­di­vo and Yer­voy in treat­ing front­line non-small cell lung can­cer cas­es.

Gio­van­ni Caforio

In a state­ment the com­pa­ny $BMY says that re­searchers tracked a “high­ly” sig­nif­i­cant pro­gres­sion-free sur­vival rate for pa­tients with a high tu­mor mu­ta­tion bur­den (TMB), re­gard­less of PD-L1 ex­pres­sion. Their com­bi­na­tion was com­pared with chemo in the study, which is still track­ing for over­all sur­vival re­sults.

That’s a sig­nif­i­cant group, an­a­lysts note, point­ing to Bris­tol-My­ers’ pro­jec­tion that the TMB crowd ac­counts for 45% of all front­line pa­tients. Bris­tol-My­ers re­designed the study to go af­ter the bio­mark­er af­ter stum­bling on a piv­otal tri­al that in­volved a pa­tient pop­u­la­tion that was not so nar­row­ly de­fined. All the de­vel­op­ers are shift­ing to a bio­mark­er fo­cus as they duke it out for spe­cif­ic slices of a mega block­buster-sized mar­ket.

Skep­tics, though, be­gan to re­tal­i­ate ear­ly, and af­ter a sharp jump ear­ly in the day, shares are trad­ing down 3% as crit­ics won­der if Bris­tol-My­ers can fol­low through with con­vinc­ing da­ta. We asked lung can­cer ex­pert Jack West for his take, which you can see here, ques­tion­ing the way the bio­mark­er was han­dled and not­ing that prac­ti­tion­ers will need to see more be­fore chang­ing the way they treat pa­tients.

Hus­tling along in search of pos­i­tive da­ta, Bris­tol-My­ers es­sen­tial­ly in­te­grat­ed two par­al­lel stud­ies in­volv­ing more than 1,700 pa­tients. And R&D chief Tom Lynch told an­a­lysts this morn­ing that there’s more work to be done on TMB-de­fined stud­ies, with up­com­ing da­ta read­outs on gas­tric, lung and head and neck can­cers.

Some an­a­lysts had been won­der­ing if Bris­tol-My­ers might just call a suc­cess to­day, with its Q4 re­port com­ing up. Past mishaps for  Op­di­vo in the all-im­por­tant NSCLC group cost it big time as Mer­ck surged ahead with a com­bi­na­tion of Keytru­da and chemo.

Just a few days ago Sea­mus Fer­nan­dez at Leerink not­ed:

While suc­cess at the OS in­ter­im rep­re­sents a very high bar, this would be a huge­ly pos­i­tive sur­prise. We be­lieve a win here would sug­gest that Op­di­vo + Yer­voy could have a crit­i­cal­ly im­por­tant place in the treat­ment of NSCLC.

Bris­tol-My­ers CEO Gio­van­ni Caforio called it a “break­through in can­cer re­search and a mean­ing­ful step for­ward in de­ter­min­ing which first-line lung can­cer pa­tients may ben­e­fit most from the com­bi­na­tion of Op­di­vo and Yer­voy.”

“TMB has emerged as an im­por­tant bio­mark­er for the ac­tiv­i­ty of im­munother­a­py. For the first time, this Phase 3 study shows su­pe­ri­or PFS with first-line com­bi­na­tion im­munother­a­py in a pre­de­fined pop­u­la­tion of NSCLC pa­tients with high TMB,” said Matthew Hell­mann, study in­ves­ti­ga­tor and med­ical on­col­o­gist at Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter. “Check­Mate-227 showed that TMB is an im­por­tant, in­de­pen­dent pre­dic­tive bio­mark­er that can iden­ti­fy a pop­u­la­tion of first-line NSCLC pa­tients who may ben­e­fit from the nivolum­ab plus ip­il­i­mum­ab com­bi­na­tion.”

Not every­one was im­pressed by the top-line re­sults, though.

The win here is al­so a plus for Foun­da­tion Med­i­cine $FMI, which pro­vid­ed the test used to pick pa­tients with a high TMB.

As­traZeneca — which ear­li­er record­ed a ma­jor fail for its com­bi­na­tion of its check­point drug Imfinzi and treme­li­mum­ab, an­oth­er PD-1/L1 check­point com­bined with an ex­per­i­men­tal CT­LA-4 drug — failed the first step on PFS with their com­bo. The OS da­ta is due out lat­er in the year.

The im­pli­ca­tions for Bris­tol-My­ers are con­sid­er­able. An ear­ly leader in the field, the R&D team on Op­di­vo have been work­ing fever­ish­ly to get their PD-1 back on track fol­low­ing a key miss in lung can­cer. But a suc­cess here on PD-1/CT­LA-4 will like­ly trig­ger fresh chat­ter of a pos­si­ble takeover bid by Pfiz­er, which has nev­er lost its ap­petite for a mega-merg­er. On the oth­er hand, such a takeover would al­so threat­en one of the most in­no­v­a­tive of the big bio­phar­ma com­pa­nies.

Op­di­vo earned close to $5 bil­lion last year, a 31% in­crease over 2016, mak­ing this their biggest sell­ing fran­chise drug. Eliquis is now their num­ber two ther­a­py, high­light­ing Op­di­vo’s over­sized role in the com­pa­ny’s fu­ture.

 

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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