Back from the dead: Nek­tar hunts a block­buster deal as opi­oid '181 looks less ad­dic­tive than oxy

Af­ter whip­ping up some up­beat an­a­lyst as­sess­ments in March with a pos­i­tive late-stage ef­fi­ca­cy study for their mu-opi­oid pain ther­a­py NK­TR-181, Nek­tar Ther­a­peu­tics has now put the fin­ish­ing touch­es to its deal pack­age on the drug with more Phase III da­ta to po­si­tion this as a first-of-its-kind opi­oid that ad­dicts can’t abuse, no mat­ter what they do to it, while ef­fec­tive­ly com­bat­ing pain.

With a big fo­cus on on­col­o­gy, Nek­tar $NK­TR has made it clear that they don’t plan to han­dle this so­lo, look­ing to ei­ther li­cens­ing it out com­plete­ly or work­ing on a co-mar­ket­ing pact. But CEO Howard Robin clear­ly wants to do this on the ba­sis that NK­TR-181 is the so­lu­tion to the opi­oid cri­sis that has been grab­bing head­lines from coast-to-coast.

And that calls for a block­buster deal, to hear him tell it.

“We’re go­ing to be fair­ly soon tak­ing all of our da­ta to the FDA,” Robin tells me.  “We have fast track sta­tus and there’s cer­tain­ly a great de­sire at the agency to see our re­sults. The reg­u­la­to­ry au­thor­i­ties un­der­stand that this is po­ten­tial­ly a so­lu­tion to the opi­oid abuse in our coun­try. No oth­er mol­e­cule like this is avail­able.”

In March the news from Nek­tar was that NK­TR-181 beat out a place­bo in re­duc­ing pain. The com­par­i­son da­ta weren’t stel­lar, but it was sig­nif­i­cant. To­day, Nek­tar wants you to know that a wide range of com­par­isons on lik­a­bil­i­ty with a range of dos­es in a head-to-head with oxy demon­strat­ed that there was a con­sis­tent and sig­nif­i­cant­ly low­er at­tach­ment to their opi­oid. Again, the da­ta points didn’t hit the ball out of the park, but they came in pos­i­tive — with the ex­cep­tion of one com­par­i­son with a 40 mg dose of oxy.

Study the end­points, says Robin, and it’s clear that this drug takes much longer than mar­ket­ed opi­oids to take ef­fect. So there’s no im­me­di­ate rush that ad­dicts are look­ing for.

“If some­one wants to abuse a drug,” he says, “they don’t want to wait 3 hours to get there. They want that 10-minute rush.”

That’s some­thing a ma­jor mar­ket­ing group could do well with in the on­go­ing cri­sis en­vi­ron­ment.

“First, you know this is pret­ty much a pri­ma­ry care mar­ket,” says Robin, and Nek­tar’s not in a po­si­tion to mar­ket to a large pri­ma­ry care au­di­ence. We’re an R&D com­pa­ny at this stage, look­ing for a part­ner who can do this. While it is an opi­oid, it’s nov­el and dif­fer­ent.” A deal “could range from a pure out-li­cens­ing agree­ment with a very sig­nif­i­cant up­front and very sig­nif­i­cant back end, or a joint ven­ture and we keep our hand in sales and mar­ket­ing.”

“This is not a for­mu­la­tion or a coat­ing,” adds the CEO. “It’s tak­en as a tablet or liq­uid with the ex­act same ef­fect. There’s re­al­ly no way to al­ter its prop­er­ties. Ap­ply any chem­istry you like. You can make it in­ef­fec­tive but you can’t sep­a­rate the opi­oid from the over­all mol­e­cule. No eu­pho­ria is as­so­ci­at­ed with 181. Chop it up. Dice it up. Turn it in­to a liq­uid. In­ject it… It’s a new opi­oid mol­e­cule that is high­ly ef­fi­ca­cious and just not like­able. For me it is a ma­jor break­through; a crit­i­cal step.”

Re­mark­ably, ‘181 failed a Phase II study in 2013. But Jef­feries’ David Stein­berg not­ed af­ter the ef­fi­ca­cy da­ta came out in March that this one was back from the dead. This pain ther­a­py could be par­tic­u­lar­ly ef­fec­tive deal­ing with chron­ic pain, es­pe­cial­ly low­er back pain. He not­ed:

As such, peak sales could be in the $1B+ range and pos­si­bly much high­er. Our new mod­el as­sumes NDA sub­mis­sion in late 2019, launch in 2H20 and 30% roy­al­ty (sim­i­lar to Amikacin In­hale) with a sig­nif­i­cant up­front and mile­stones in ex­cess of $200M.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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As­traZeneca scores new goal on the pipeline front, adding its first AI-gen­er­at­ed tar­get to the port­fo­lio

As more and more biopharmas develop artificial intelligence platforms, the drug discovery process is being reshaped to fit new goals on cutting down the prodigious amount of time, energy and money that go into a drug program. Now one of the most ambitious players in the drive to improve on ROI, AstraZeneca, is marking a milestone on that front by adding the first target generated by AI to its portfolio.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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