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

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.