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.

 

Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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J&J team shows off 'break­through' BC­MA CAR-T da­ta, and that could cause a big headache at blue­bird and Bris­tol-My­ers

Just hours after J&J’s oncology team bragged about scoring a breakthrough therapy designation for their BCMA CAR-T drug, they pulled the wraps off of the multiple myeloma data for JNJ-4528 that impressed the FDA. And it’s easy to see why they may well be on a short path to a landmark approval — which may well be making the rival team at bluebird/Bristol-Myers more than a little nervous.

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J&J's Mathai Mammen at an Endpoints News event in Boston, June 2018 (Photo: Rob Tannenbaum for Endpoints News)

J&J fronts $750M cash to grab a failed can­cer drug that’s been re­pur­posed as a pow­er­ful an­ti-in­flam­ma­to­ry

J&J has stepped up with one of its blockbuster drug buys, agreeing to pay Austin-based XBiotech $XBIT $750 million in cash and up to $600 million more in milestones for their late stage-ready anti-inflammatory drug bermekimab — which some longtime biotech observers may recognize as a failed cancer therapy with a disaster-prone past.

The drug targets the IL-1a pathway. J&J $JNJ R&D chief Mathai Mammen is cutting a check for a drug that has produced positive mid-stage data in patients suffering from a skin condition called hidradenitis suppurativa with another mid-stage program underway for atopic dermatitis.

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Sangamo CEO Sandy Macrae

Pa­tient #9 has been a con­cern, but Sang­amo and Pfiz­er are bull­ish about win­ning the marathon he­mo­phil­ia A gene ther­a­py race

Patient number 9 has given Sangamo and its partners at Pfizer some heart palpitations in their high profile hemophilia A gene therapy program.

After watching his Factor VIII level rise following treatment like the rest, the crucial efficacy gauge they track saw a sudden and significant plunge. At week 13, the FVIII level had dropped below normal. Then it began to rise again.

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Un­lock the full End­points ex­pe­ri­ence for your com­pa­ny — and sup­port our mis­sion of in­de­pen­dent bio­phar­ma re­port­ing

I want to give readers a quick update on the most important part of our business model — premium subscriptions. We have some crucial financial goals we hope to achieve by the end of the year, and the team here in Lawrence is ready to ship some swag to kick off this limited December promotion.

We offer two premium plans — Enterprise for companies ($1,000/year, unlimited people), and Insider for individuals ($200/year). This month of December will be the last chance to enroll at the original rates — which have remained flat since we launched them in 2017.

One of Wall Street’s most high-pro­file hedge funds push­es Alex­ion's CEO to the auc­tion block — and he's not budg­ing

Fresh off buying Barnes & Noble and prodding AT&T with some heavy-handed criticism after picking up a $3.2 billion stake in the company, the activist — and supremely high profile — hedge fund Elliott Management has stepped up with some M&A advice for Alexion’s management team.
And the execs on the team $ALXN are giving them a polite — but very firm — stiff arm Friday morning.
In a release out early Friday, the big biotech said that the Elliott team had been in touch to encourage them to sell the company. But that’s not on the agenda.

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Samantha Budd Haeberlein. Biogen via YouTube

UP­DAT­ED: Skep­tics pounce as Bio­gen de­tails pos­i­tive sub­group analy­sis on ad­u­canum­ab — and both sides are dig­ging in

“Exhilarating.” “A major advance.” “A milestone achievement.” If one had just tuned into the panel comments on Biogen’s presentation at CTAD, it would seem that the biotech had an impressive, disease-modifying Alzheimer’s drug in aducanumab.

But off the stage, reactions to their admittedly complicated dataset and the biotech’s explanation for resurrecting a drug that failed its futility analysis were a lot more mixed, with analysts continuing to question whether the evidence is substantial enough to warrant an FDA approval and raising new doubts on the safety side.

In an investor call later in the day, execs noted that they are not planning another study and stood by their intention, publicized in October to much surprise, to submit regulatory filings based on what they have.

“We don’t file willy nilly,” said Al Sandrock, head of R&D. “We only go to filing when we believe that there is a benefit-risk argument based on science, based on data. And if you look at our history, we haven’t done filings right and left without good reason.”

Biogen had a theory going into the Clinical Trials on Alzheimer’s Disease meeting.

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Vas Narasimhan, Getty Images

No­var­tis CEO Vas Narasimhan's R&D up­date spot­lights next wave of drug stars as well as late-stage fa­vorites

As one of the biggest spenders in biopharma R&D, Novartis execs love to tout the scope of its late-stage pipeline, spotlighting the winners most likely to create blockbuster revenue streams in the near future.

Building on the 5 drug approvals the pharma giant expects to end the year with, Novartis CEO Vas Narasimhan — who’s done a slate of acquisitions topped by the recent $9.7 billion MedCo buyout — tapped the top emerging drugs as:

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Jeff Jonas, Sage

UP­DAT­ED: Sage's star ex­per­i­men­tal de­pres­sion drug fails the cru­cial MOUN­TAIN study — shares crash

Sage Therapeutics’ crucial MOUNTAIN study for Sage-217 has failed, setting the stage for a quick and ugly investor backlash.

Widely viewed by analysts as the critical clinical study $SAGE needed to win on major depression, researchers say the drug failed to beat out a placebo at day 15, falling well short of the mark for statistical significance on the primary endpoint. And investors reacted with alacrity, fleeing the stock and gutting the price with a 60% instantaneous drop — erasing about $4.6 billion in market cap in an instant.

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