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

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Sen­ate Fi­nance Com­mit­tee lobs more bi­par­ti­san pres­sure on­to PBMs

Congress is honing in on how it wants to overhaul the rules of the road for pharmacy benefit managers, with a Senate Finance Committee hearing Thursday serving as the latest example of the Hill’s readiness to make changes to how pharma middlemen operate.

While pledging to ensure patients and pharmacies “don’t get a raw deal,” Finance Committee Chair Ron Wyden (D-OR) laid out the beginning of what looks like a major bipartisan effort — moves the PBM industry is likely to challenge vigorously.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Nicklas Westerholm, Egetis Therapeutics CEO

Ac­qui­si­tion talks on­go­ing for Swedish rare dis­ease biotech Egetis, shares up al­most 40%

Shares of the Sweden-based rare disease biotech Egetis Therapeutics skyrocketed on Thursday afternoon as the company said it’s engaged in “ongoing discussion” with external parties regarding a “potential acquisition.”

Egetis confirmed rumors with a statement on Thursday while noting that there is no certainty that a takeover offer will be made.

Nonetheless, the possibility of an acquisition has shot up Egetis’ share price. By the afternoon on Thursday, its stock price was {$EGTX.ST} up over 38%. An Egetis spokesperson told Endpoints News in an email that it has no further comments.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Lu­pus drug de­vel­op­ment mar­ket heat­ing up, while FDA links with ad­vo­ca­cy group to fur­ther ac­cel­er­ate re­search

The long-underserved systemic lupus erythematosus (SLE) market is suddenly buzzing with treatment possibilities. Less than two years after AstraZeneca’s approval for Saphnelo — the first new SLE drug in a decade and joining just one other approved in GSK’s Benlysta – the pipeline of potential drugs numbers in the dozens.

Although most are very early stage — Spherix Global Insights estimates five in Phase II/III — the pharma R&D enthusiasm is catching on among doctors, patients and advocacy groups. On Wednesday, the Lupus Research Alliance and the FDA formed a novel private-public partnership called Lupus Accelerating Breakthroughs Consortium (Lupus ABC) to help advance lupus clinical trial success.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Af­ter safe­ty re­view, EMA mir­rors FDA with up­dat­ed rec­om­men­da­tions for JAK in­hibitors

The EMA released updated recommendations today for the use of JAK inhibitors (JAKi) after reviewing data from several clinical trials that showed increased incidents of issues in certain patients who have rheumatoid arthritis and other risk factors.

The EMA noted malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality in some patients.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.