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.

 

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

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UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

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At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

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Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

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CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.