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.

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

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Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

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No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

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No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

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As­traZeneca gains EU nod for di­a­betes triple; Am­gen and Duke launch re­al-world PC­SK9 ob­ser­va­tion­al study

→ Weeks after winning EU approval to start marketing dapagliflozin as Forxiga, AstraZeneca has racked up another OK for a triplet combo involving the SGLT2 diabetes drug. Named Qtrilmet, the pill combines Forxiga with the DPP-4 inhibitor Onglyza (saxagliptin) and the bedrock drug metformin in a modified-release format. That 3-in-1 approach proved superior in reducing average blood glucose levels to a number of other dual combinations across 5 Phase III trials, including Forxiga plus metformin, Onglyza with metformin, or glimepiride with metformin.

Five drugs, in­clud­ing two No­var­tis ther­a­pies, win EMA en­dorse­ment

As is custom, an EMA panel on Friday issued its weekly recommendations on marketing applications submitted by drug developers. This week, the agency backed the use of five new therapies — including two Novartis drugs — but issued no negative reviews.

Novartis’ S1P drug for relapsing forms of multiple sclerosis (MS) drug, Mayzent (known chemically as siponimod), which was approved by the FDA in March — has been given the nod by the EMA. The Swiss drugmaker already sells its other MS drug, Gilenya, in both regions.

Atom­wise's X-37 spin­out gets $14.5 mil­lion to launch AI dis­cov­ery ef­forts

The folks behind Atomwise’s spinout X-37 like to think in cosmological metaphors, and you can think of their AI drug development model as probes sent into space from a central station. That station just got $14.5 million in Series A funding from DCVC Bio, Alpha Intelligence Capital and Hemi Ventures to back those missions.

X-37 uses Atomwise’s AI platform to identify drug targets and – unlike the parent company, which largely sticks to computers  – bring those into a wet lab and preclinical testing.  In addition to AI professionals, it’s led in by part by drug developers from Velocity Pharmaceutical Development.

Ab­bott Lab­o­ra­to­ries CEO Miles White pass­es ba­ton down to suc­ces­sor; Lon­za CEO Marc Funk hits the ex­it

→ Abbott Laboratories has named a successor to CEO Miles White after he announced that he was stepping down in March after 21 years of service. Robert Ford, the company’s COO and president, will take the helm. Ford is known for his work in the $25 billion merger between St. Jude Medical into Abbott in January 2017. White will remain with the company as executive chairman of the board. 

→ After snapping up Novartis’ Swiss facility, Novartis Center of Excellence, in July, Lonza has announced that their CEO, Marc Funk, is hitting the exit for “personal reasons.” Funk has been the CEO of the company for less than a year — brought onto the company back in March. In the meantime, chairman Albert Baehny will serve as interim CEO. 

UCB adds on more pos­i­tive PhI­II da­ta for IL-17A/17F in­hibitor bimek­izum­ab, clear­ing a path to the FDA

A month after posting positive top-line data from their first Phase III trial of the IL-17A/17F inhibitor bimekizumab, Belgium’s UCB says they’ve added more upbeat results from their second late-stage test in moderate-to-severe plaque psoriasis.

That leaves the company on track for regulatory submissions in the middle of next year, says CMO Iris Loew-Friedrich.
Their drug beat out a placebo on the co-primaries — a 90% improvement in PASI 90 (the Psoriasis Area and Severity Index) and Investigator Global Assessment (IGA) response of clear or almost clear (IGA 0/1) at week 16, compared to placebo. Investigators also boasted of hitting some key secondaries.
UCB is angling to enter an increasingly crowded market space.
In their first of 3 Phase III studies for bimekizumab, researchers touted top-line wins on statistically significant results on clearing plaque psoriasis, including a victory over J&J’s IL-23 contender Stelara on key endpoints. The drug targets both IL-17A and IL-17F, a modification on the IL-17A strategy laid out for Taltz (Eli Lilly) and Cosentyx (Novartis). And the new group also includes J&J’s Tremfya and AbbVie’s Skyrizi.

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