Af­ter kick­back from the FDA, Bris­tol-My­ers yanks its Op­di­vo/Yer­voy BLA for high TMB ap­proach to lung can­cer

Bris­tol-My­ers Squibb has had a hard time win­ning an­a­lysts over to its strat­e­gy for carv­ing out a high­er mar­ket share for its check­point com­bo in non-small cell lung can­cer. And now you can add the FDA to the list of skep­tics re­quir­ing more da­ta to con­vince them.

In their Q4 re­lease Thurs­day morn­ing Bris­tol-My­ers Squibb says it is yank­ing its BLA for Op­di­vo com­bined with Yer­voy for front­line NSCLC cas­es with high tu­mor mu­ta­tion­al bur­den — or TMB — af­ter talks with the agency con­vinced them they need­ed more da­ta to high­light the con­nec­tion be­tween TMB and PD-L1.

Their state­ment:

This analy­sis will re­quire avail­abil­i­ty of the fi­nal da­ta from Check­mate -227, Part 1a (Op­di­vo plus low-dose Yer­voy or Op­di­vo monother­a­py ver­sus chemother­a­py in pa­tients whose tu­mors ex­press PD-L1), which the com­pa­ny an­tic­i­pates will be avail­able in the first-half of 2019. Since these da­ta from Check­mate -227, Part 1a, will not be avail­able with­in the re­view cy­cle of the cur­rent ap­pli­ca­tion the com­pa­ny de­cid­ed to with­draw.

Bris­tol-My­ers’ stock took a 2.4% hit in trad­ing ahead of the open­ing bell.

Long­time ob­servers have been puz­zling out the whole TMB ap­proach, which As­traZeneca has al­so been turn­ing to in the wake of its own PD-L1/CT­LA-4 set­backs with Imfinzi and treme­li­mum­ab. Bris­tol-My­ers re­designed its crit­i­cal late-stage tri­al to shift to TMB, and it has not played out in their fa­vor — so far.

Af­ter Mer­ck seized the lead in lung can­cer with its su­pe­ri­or Keytru­da/chemo com­bo, Bris­tol-My­ers’ team led by R&D chief Tom Lynch has been strug­gling to make a come­back. Typ­i­cal­ly, the FDA has been wide open — at least in re­cent years — to ac­cel­er­at­ed ap­provals for can­cer drugs. In this case, Bris­tol-My­ers found that the bar has been raised as physi­cians em­ploy a grow­ing num­ber of PD-1/L1s in their prac­tice.

Cred­it Su­isse’s bio­phar­ma team took at look at the news and con­clud­ed that, on bal­ance, Bris­tol-My­ers’ move rais­es fresh con­cerns.

We did not think an ap­proval for that fil­ing would have made much of a near-term com­mer­cial im­pact any­way, but it does raise new ques­tions on the com­pa­ny’s over­all strat­e­gy and ap­proach in 1L NSCLC.

In an up­date last Oc­to­ber, re­searchers for Bris­tol-My­ers not­ed that the haz­ard ra­tio for their com­bo was roughy iden­ti­cal for high and low TMB groups get­ting the com­bo, but the over­all sur­vival rate was 23 months for high TMB pa­tients at 16.7 months in a chemo arm with high TMB. There was al­so a dif­fer­ence of a few months for the low TMB group.

The set­back comes just weeks af­ter Bris­tol-My­ers an­nounced its plan to ac­quire Cel­gene for $74 bil­lion. And to­day there was a big fo­cus on the top late-stage drugs they will gain from Cel­gene: Ozan­i­mod, with a Q1 re­fil­ing plan; the CAR-T Liso-cel (JCAR017 from the Juno buy­out), with an H2 2019 fil­ing plan; and the an­ti-BC­MA CAR-T bb2121 part­nered with blue­bird, fil­ing in H1 2020. All that has to counter ques­tions re­volv­ing around the IP for Revlim­id.

The lat­est prob­lem with the Op­di­vo fran­chise over­shad­owed the com­pa­ny’s Q4 and 2018 fi­nan­cial re­port, which high­light­ed a 10% hike in sales. Op­di­vo it­self earned $6.7 bil­lion last year, up from just un­der $5 bil­lion in 2017. The rest of the ap­proved slate pf PD-1/L1s has been strug­gling to get in­to the same league with Mer­ck and Bris­tol-My­ers Squibb.


Im­age: Thomas Lynch at BIO 2018. ROB TAN­NEN­BAUM for END­POINTS NEWS

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Turn­ing the cor­ner on treat­ing the root cause of sick­le cell dis­ease

Early in my career, as a medical resident, I saw first-hand the enormous challenges faced by children and adults with sickle cell disease (SCD), a genetic blood disorder that historically has lacked adequate treatment options. People living with this life-long disease are mainly those with ancestors from sub-Saharan Africa, as well as people of Hispanic, South Asian, Southern European and Middle Eastern descent. These patients suffer from devastating physical symptoms, including progressive, eventually fatal, organ damage and excruciating pain. In addition, they encounter emotional, mental and social burdens – non-physical aspects of living with SCD that also take a serious toll on patients and their caregivers.

Rev­o­lu­tion Med shoots for $100M+ IPO — and di­vulges some se­crets about that Warp Dri­ve buy­out

Biotech investors who like to wager on the race to the front of the KRAS market now have a new team to consider.

Revolution Medicines, which extended its reach on RAS with a deal to acquire Warp Drive Bio about 18 months ago, filed their S-1 in search of $100 million-plus. And they gave up a few secrets in the process.

The main clinical claim to fame that Revolution has centers on the SHP2 inhibitor RMC-4630, partnered with Sanofi back in the summer of 2018 — just after John Reed was named the incoming R&D chief. We already knew that the pharma giant handed over $50 million in cash plus a commitment of hundreds of millions more to align itself with Revolution as it makes a fresh foray into oncology. Now we know that Sanofi is also footing 80% of Revolution’s R&D bill on the program, while setting up a smorgasbord of $235 million in development milestones and $285 million in commercial bonuses.

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Olivier Brandicourt, AP Images

#JPM20 ex­clu­sive: Olivi­er Brandi­court fol­lows the Big Phar­ma CEO path to pri­vate eq­ui­ty, join­ing Black­stone ahead of a mam­moth fund de­but

Nick Galakatos Blackstone

Seven months after Olivier Brandicourt’s surprise “early retirement” from Sanofi, he’s back in the game, this time taking meetings at JP Morgan to discuss his new role at Blackstone, where he’s quietly begun work with Nick Galakatos and the life sciences crew.

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Video Re­play: End­points at #JPM20 — news­mak­ers on deal­mak­ing, pric­ing and man­u­fac­tur­ing

On Monday, we held our fourth annual #JPM event — and the team hit a key milestone that I’d like to share with the entire Endpoints News audience: We live-streamed the conversation and had nearly triple the number of executives watching online than we had in the sold-out crowd of 320.

For a media company on a mission to connect the biopharma world in bigger and better ways, we’re proud of how we were able to extend the reach of our franchise event. Paid subscribers were given access to the stream in real time, and now, two days later, we’re opening it up to everyone in this post.

Endpoints@JPM: (left to right) Steve Pearson, Nick Leschly, Bari Talente, Stephen Ubl, John Carroll

#JPM20: 'The NPV is al­ways wrong.' Take­da preps an­oth­er spin­out — this time on psych

Editor’s Note: Endpoints News is reporting live from #JPM20 after kicking things off with an action-packed event, which you can replay here. What follows is a stream of tidbits we have collected while wandering around Union Square in San Francisco. Check back in throughout the week for updates by John Carroll and Jason Mast.

SAN FRANCISCO — A year ago Takeda CEO Christophe Weber and R&D chief Andy Plump arrived at JP Morgan right on the heels of closing their big Shire buyout. Now they’re back after shaking up the portfolio, boosting R&D spending by about 50% to $4.5 billion and adjusting the pipeline — a task which isn’t quite finished yet.

Nick Leschly at Endpoints News' panel at the 2020 JP Morgan Healthcare Conference. Credit: Jeff Rumans

At #JPM20, two CEOs, two rad­i­cal­ly dif­fer­ent ther­a­pies, and a fight to chase down sick­le cell

SAN FRANCISCO – Few CEOs tell a story better than bluebird’s Nick Leschly.

He cuts a Jeff Bezos figure on stage at the Colonial Room, the JP Morgan presentation hall for A-list biotechs: lean and bald, fast-talking and vest-wearing. He explains in simple language, apologizing when he has to brush on the data. It helps that he has a good story to tell.

“We treated them one time,” Leschly tells a packed crowd, gesturing to the slide behind him. “Look what happened.”

The slide shows 9 horizontal bars studded with diamonds. Each bar, he explained, represented a sickle cell patient, and each diamond represented a severe medical event, such as a pain crisis. The diamonds stud one side – before the therapy – and vanish on the other, afterward.

“A 99% reduction in these events — this is a functional cure for sickle cell disease,” Leschly says. “This is unprecedented data.”

Upstairs and an hour later, Ted Love stands before a narrow conference room in his suit and polka-dot tie. Love, the CEO of Global Blood Therapeutics, is a 60-year-old physician. His voice trails off at the end of sentences, and the story he tells is less compelling. There are no cured patients.

“This is the first drug that addresses the root cause of sickle cell disease,” Love says, speaking in front of a slide showing a white pill bottle for GBT’s new drug Oxbryta. “Right in the label, it says that this drug inhibits polymerization.”

In the 60 years after scientists discovered the cause of sickle cell, almost no treatments emerged, even as the condition debilitated hundreds of thousands of Americans, most of them black or Hispanic. But the last few years have seen a resurgence of interest as new technologies have made the disease seem newly beatable.

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Neon Ther­a­peu­tics makes one last re­treat, sell­ing it­self cheap in a bar­gain base­ment M&A deal

Crushed by weak data for what had been their lead drug, Neon Therapeutics is being bought for parts this morning.

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Mark Pruzanski

#JPM20: Af­ter a year of NASH col­laps­es, all eyes on two biotechs

SAN FRANCISCO – It’s not quite Dewey defeats Truman, but Goldman Sachs calling 2019 “The Year of NASH” may well go down in the annals of worst biotech predictions.

Goldman Sachs slapped the label on weeks before 2019’s JP Morgan conference, projecting that long-discussed treatments for the obesity-driven condition suspected to lurk in millions of Americans would begin to bear fruit and investors would move accordingly. That did not quite happen.

“If you look at 2019, it was just a string of disappointing news,” Pascal Prigent, CEO of NASH-focused biotech Genfit, told Endpoints News in an interview.

The Year of NASH, or nonalcoholic steatohepatitis, became a year of NASH failures. Gilead failed two large Phase III trials. CymaBay went from a $1 billion company to a $100 million company after they found their drug was killing patients’ liver cells. Cirius withdrew an $86 million IPO bid after a disastrous readout. Industry-wide, there were few acqusitions in a market often projected to be worth $35 billion.

Gilead, after dominating the NASH discussion at the 2019 JPM, gave one quick mention to the program in their 2020 presentation before pivoting to other drugs.

“As promising as some of the mechanisms looked in earlier stages, when push comes to shove in large study settings, they just haven’t proven out,” Mark Pruzanski, CEO of the NASH-focused biotech Intercept, told Endpoints in an interview.

As biotech turns from 2019, the failures have refocused eyes away from Gilead and back toward two startups, both facing key events in the coming months: Intercept, which first alerted investors to NASH at JPM 2014, and the France-based Genfit.

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