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

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Sanofi takes a $260M hit to ex­tri­cate it­self from a dis­as­trous al­liance with Lex­i­con

Sanofi spent $300 million in cash to get into a $1.7 billion alliance with Lexicon on their SGLT1/2 diabetes drug sotagliflozin. And now that the drug has been spurned by the FDA after burning through a program that provided mixed late-stage data and a late shot at a last-place finish, the French pharma giant is forking over another $260 million to get out of the deal.

Sanofi’s unhappiness was already apparent when the company — now under new CEO Paul Hudson — posted a statement back in July that they were dropping the deal. But it wasn’t that simple. 

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.