The lat­est up­date on NK­TR-214/Op­di­vo from Nek­tar and Bris­tol-My­ers will keep the con­tro­ver­sy burn­ing over the ORR rate

Nek­tar Ther­a­peu­tics $NK­TR man­aged to slide 1 out of its 38 evalu­able stage 4 melanoma pa­tients in­to the win col­umn with its close­ly-watched 3-month up­date on Op­di­vo/NK­TR-214’s ob­jec­tive re­sponse rate. That man­aged to nudge up the ORR from 50% — a fig­ure that rout­ed Nek­tar’s stock at AS­CO — to 53%, which isn’t like­ly to con­vince any of the crit­ics that the biotech and its part­ners at Bris­tol-My­ers Squibb have come up with the kind of com­bo that can change the stan­dard of care in the field.

But if you ex­pect any­one di­rect­ly in­volved in this study to step back from the en­thu­si­as­tic pro­jec­tions that were made on the first op­ti­mistic da­ta points, you’d be flat wrong.

Adi Diab

While the cru­cial ORR bare­ly budged, Adi Diab from MD An­der­son point­ed straight to a high­er com­plete re­sponse rate, at 24% — “which is not seen with an­oth­er com­bi­na­tion.” He’s al­so of­fer­ing a thumbs up to a 76% dis­ease con­trol rate — up from 71% at AS­CO — as ev­i­dence that they’re on to some­thing spe­cial.

Sev­er­al an­a­lysts — in­clud­ing some in the Ever­cor­eISI team — had been look­ing for some­thing in the 60%-plus range for the ORR to win back the en­thu­si­asm that has drained away for NK­TR-214, a drug that a needy Bris­tol-My­ers Squibb paid $1.85 bil­lion up­front to part­ner on ear­li­er in the year. The drug is de­signed to bind to the CD122 re­cep­tor on the sur­face of CD-8 and CD-4 pos­i­tive im­mune cells to whip up an at­tack on var­i­ous can­cers.

And Diab says they can see ex­act­ly that re­sponse in pa­tients with pos­i­tive bio­mark­er re­sults for the tu­mor mi­croen­vi­ron­ment.

As it stands, the re­searchers have a drug that ap­pears to have clear­ly waned in the more ma­ture 7.2-month me­di­an fol­lowup time for PIV­OT-02, drop­ping from 64% at the first cut of the da­ta at SITC last year. And just days ago Bris­tol-My­ers out­lined im­pres­sive 4-year over­all sur­vival re­sults from Check­Mate-067: 53% for Op­di­vo plus Yer­voy com­bo, 46% for Op­di­vo alone, and 30% for Yer­voy alone.

Diab, though, be­lieves that with bet­ter ex­pe­ri­ence us­ing the drug, and bet­ter ed­u­ca­tion for physi­cians and pa­tients, the re­sponse rate can climb back up to 60%-plus. As for Yer­voy, he adds, the CT­LA-4 has a well known tox pro­file that leads to a high rate of ad­verse events that of­ten pre­vent pa­tients from com­plet­ing treat­ment.

“We should not do com­par­isons with oth­er tri­als, it’s not kosher,” Diab tells me at one point in our con­ver­sa­tion. “But of course we’re go­ing to do it.”

There’s been some in­tense con­tro­ver­sy over their chances with this IL-2 drug, which us­es pe­gy­la­tion tech to elim­i­nate the draw­backs of the orig­i­nal ther­a­py – Pro­leukin — that made it too tox­ic to use at full mea­sure, in turn lim­it­ing its ef­fi­ca­cy.

One like­ly take­down of the Nek­tar de­fense should come soon from Aaron Wed­lund, the ex-Ker­ris­dale an­a­lyst who wrote a lengthy di­a­tribe on NK­TR-214, which he con­sid­ers will make IL-2 the next IDO, an­oth­er drug class once wide­ly hailed as the next big thing in can­cer drug com­bos now bad­ly tar­nished fol­low­ing a cat­a­stroph­ic Phase III com­bo fail­ure with Keytru­da.

Bris­tol-My­ers en­thu­si­as­ti­cal­ly bought in­to the next-gen IL-2 drug ap­proach as it’s been un­suc­cess­ful­ly de­fend­ing its PD-1/L1 crown against a hard-charg­ing Mer­ck, which has pushed Keytru­da and chemo com­bos in­to the fore­front of the lung can­cer mar­ket. IL-2, they said, would be the next log­i­cal step to PD-1 and CT­LA-4, with Yer­voy.

Any­thing that puts this drug back in the Pro­leukin cat­e­go­ry, with more IL-2 suc­ces­sors in the pipeline, won’t be wel­come by the de­vel­op­ers.

It’s im­por­tant to keep in mind that a bunch of short in­vestors had fun — and made mon­ey — pulling Nek­tar’s stock down from some stun­ning highs that it had en­joyed. Rais­ing doubts is good for spurring cor­rec­tions, and Nek­tar’s stock has tum­bled bad­ly. The ju­ry will re­main out, though, un­til the Phase III pro­gres­sion-free sur­vival da­ta comes due around the spring of 2020.

Un­til then, and maybe even af­ter, this de­bate will con­tin­ue to rage.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.