An­oth­er opi­oid pain drug, re­al­ly? FDA staff sound sour on Nek­tar anal­gesic

The cri­sis of opi­oid abuse, mis­use, and over­dose in the Unit­ed States has made the FDA a tough crit­ic of any opi­oid painkiller up for re­view. Nek­tar’s anal­gesic, NK­TR-181, is no ex­cep­tion.

The drug is a re­duced form of the wide­ly-abused oxy­codone — it is for­mu­lat­ed in a way that in­creas­es the half-life and di­min­ish­es the rate of en­try in­to the brain, ac­cord­ing to Nek­tar, which be­lieves that NK­TR-181’s 16 times slow­er en­try in­to the brain ver­sus oxy­codone will help de­ter abuse — but in brief­ing doc­u­ments post­ed on Fri­day, FDA staff did not sound con­vinced, high­light­ing that the for­mu­la­tion is not en­gi­neered to fa­cil­i­tate abuse de­ter­rence from phys­i­cal ma­nip­u­la­tion.

In par­tic­u­lar, agency re­view­ers un­der­scored that NK­TR-181 demon­strates an oral abuse po­ten­tial com­pa­ra­ble to oxy­codone and that there was in­suf­fi­cient da­ta to de­ter­mine the abuse po­ten­tial of the anal­gesic to al­low a de­ter­mi­na­tion of abuse po­ten­tial for NK­TR-181 via the in­tra­venous and in­tranasal route of ad­min­is­tra­tion.

Nek­tar — which spun the drug, once tout­ed as a block­buster, off in­to sub­sidiary op­er­a­tion, af­ter ini­tial­ly seek­ing a part­ner — is look­ing for ap­proval in pa­tients with chron­ic low back pain. It test­ed the ef­fi­ca­cy and safe­ty of the anal­gesic in one late-stage tri­al and sub­mit­ted safe­ty da­ta on pa­tients with oth­er chron­ic non­cancer pain.

FDA re­view­ers asked the in­de­pen­dent pan­el of ad­vi­sors who will de­lib­er­ate on the drug on Tues­day to pon­der whether the one piv­otal study back­ing the drug’s ef­fi­ca­cy and safe­ty was enough — con­sid­er­ing Nek­tar was ad­vised to con­duct two tri­als.

Liv­er safe­ty ap­peared to be an­oth­er con­cern — FDA re­view­ers asked pan­elists to dis­cuss whether any ad­di­tion­al safe­ty da­ta are need­ed, con­sid­er­ing pa­tients may use NK­TR-181 at dos­es high­er than those test­ed.

In ad­di­tion, re­view­ers ap­peared to ask pan­elists to de­lib­er­ate whether the drug was nec­es­sary at all, giv­en that opi­oids should not be used as the ini­tial ther­a­py for pa­tients with chron­ic low back pain or those that have not re­spond­ed ad­e­quate­ly to non-opi­oid and non-phar­ma­co­log­ic ther­a­pies.

“Brief­ing doc­u­ments re­leased…read neg­a­tive­ly to us, with lan­guage re­flect­ing a lack of FDA com­fort re­gard­ing the ef­fi­ca­cy and safe­ty of -181 and its po­ten­tial for abuse. Con­sis­tent with the low ex­pec­ta­tions we had for pro­gram, we an­tic­i­pate a ma­jor­i­ty vote against ap­proval,” SVB Leerink’s Daina Gray­bosch wrote on Fri­day.

“We ex­pect a tough re­cep­tion for any opi­oid ap­pli­ca­tion giv­en the on­go­ing pub­lic health cri­sis. There is noth­ing in the brief­ing docs to sug­gest that FDA sees any­thing in NK­TR-181 to jus­ti­fy the safe­ty risk of ap­prov­ing a new opi­oid to mar­ket. There are four draft ques­tions up for de­bate, which the FDA framed, in our opin­ion, to lead to a very crit­i­cal dis­cus­sion of -181’s mer­its.”

The ad­vi­so­ry pan­el will con­vene on Tues­day. The FDA is not bound by the rec­om­men­da­tions of the pan­el but tend to fol­low them.

So­cial im­age: Nek­tar

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

UP­DAT­ED: End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

(This piece was last updated on August 13. Endpoints News will continue to track the latest developments through the FDA’s marketing decisions.)

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

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Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

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James Wilson, WuXi Global Forum at JPM20

FDA puts up a red light for Pas­sage Bio’s first gene ther­a­py pro­gram, de­lay­ing a pro­gram from James Wilson's group at Penn

Gene therapy pioneer James Wilson spearheaded animal studies demonstrating the potential of new treatments injected directly into the brain, looking to jumpstart a once-and-done fix for an extraordinarily rare disease called GM1 gangliosidosis in infants. His team at the University of Pennsylvania published their work on monkeys and handed it over to Passage Bio, a Wilson-inspired startup building a pipeline of gene therapies — with an IND for PBGM01 to lead the way.

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Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Qi­a­gen in­vestors spurn Ther­mo Fish­er’s takeover of­fer, de­rail­ing a $12B+ deal

Thermo Fisher Scientific had announced an $11.5 billion takeover of Dutch diagnostics company Qiagen back in March, but the deal apparently did not sit well with Qiagen investors.

After getting hammered by critics who contended that Qiagen $QGEN was worth a lot more than what Thermo Fisher wanted to spend, investors turned thumbs down on the offer — derailing the buyout even after Thermo Fisher increased its offer to $12.6 billion in July. Qiagen’s share price has been boosted considerably by Covid-19 as demand for its testing kits surged.

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Xuefeng Yu in Hong Kong, 2019 (Imaginechina via AP Images)

CanSi­no reaps $748M wind­fall from Shang­hai IPO — as it warns Covid-19 vac­cine won't be a huge mon­ey mak­er

CanSino began the year with a clear goal to secure a secondary listing on Shanghai’s STAR market. Then something more urgent came along: As a rising vaccine developer on a mission to bring global standard immunizations to China, it heeded the call to make a vaccine to protect against a virus that would paralyze the whole world.

Xuefeng Yu and his team managed to keep doing both.

More than a month after CanSino’s Covid-19 vaccine candidate is authorized for military use in China, the Hong Kong-listed company has made a roaring debut in Shanghai. It fetched $748 million (RMB$5.2 billion) by floating 24.8 million shares, and soared 88% on its first trading day.