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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Terrie Curran, Phathom CEO (Credit: Arcutis)

Phath­om's old Take­da drug bests Pre­vacid in a PhI­II GI tri­al. Next stop? The FDA

There’s no time for rest in biopharma — at least not at Phathom Pharmaceuticals. Just over a month after submitting two NDAs for its lead acid-fighter vonoprazan, the biotech is already lining up a third, and collecting an extra $50 million to push things along.

Vonoprazan met its primary non-inferiority endpoints in a Phase III study comparing it to standard-of-care Prevacid in a type of gastroesophageal reflux disease (GERD) called erosive esophagitis (EE). It also proved superior to the popular heartburn drug by multiple measures, including healing rate and maintenance of healing.

Thomas Lingelbach, Valneva CEO

Small biotech says its Covid-19 vac­cine spurs more an­ti­bod­ies than As­traZeneca’s. Will sup­ply deals come now?

In a first, a small runner-up vaccine developer says its own Covid-19 jab has induced “superior neutralizing antibody titer levels” over AstraZeneca’s AZD1222 when pitted head-to-head in a Phase III trial.

That and non-inferiority in seroconversion rate were the co-primary endpoints of the trial, which recruited 4,012 adult volunteers across the UK.

But on the exploratory endpoint of Covid-19 case counts, Valneva notes that both treatment groups saw a similar number of infections.