Hung ju­ry vote leaves FDA with a dif­fi­cult de­ci­sion on Durec­t's non-opi­oid painkiller

A split ad­vi­so­ry pan­el vote on Durect’s non-opi­oid drug to man­age post-sur­gi­cal pain is on­ly go­ing to make the FDA’s task hard­er.

Af­ter FDA staff re­view­ers is­sued an in­ter­nal re­view that un­der­scored their un­ease with the side-ef­fect pro­file of the long-act­ing anes­thet­ic posimir — on Thurs­day a pan­el of in­de­pen­dent ex­perts could not reach a con­sen­sus on whether to back the ther­a­py.

Six pan­elists en­dorsed ap­proval, while the re­main­ing six dis­sent­ed. The ther­a­py is a for­mu­la­tion of the anes­thet­ic bupi­va­caine and is de­signed to man­age pain up to three days fol­low­ing surgery af­ter be­ing ad­min­is­tered di­rect­ly in­to the sur­gi­cal in­ci­sion.

Posimir has a check­ered past. Durect, which orig­i­nal­ly part­nered with No­var­tis on the pro­gram, first sub­mit­ted an ap­pli­ca­tion to mar­ket on the ba­sis of two piv­otal stud­ies. The FDA spurned the ap­pli­ca­tion in 2014 over safe­ty con­cerns. Durect then con­duct­ed the PER­SIST study, hop­ing to quell the agency’s con­cerns — but that tri­al failed its main ef­fi­ca­cy goal. Nonethe­less, Durect re­sub­mit­ted a mar­ket­ing ap­pli­ca­tion.

The US drug reg­u­la­tor has in­ten­si­fied its ef­forts to stem the tide of opi­oid abuse, over­dose, and ad­dic­tion, fierce­ly scru­ti­niz­ing the phar­ma­ceu­ti­cal ar­chi­tects of the pre­scrip­tion painkiller cri­sis. So de­spite per­sis­tent safe­ty con­cerns as­so­ci­at­ed with posimir, the prospect of ‘opi­oid-spar­ing’ was ap­peal­ing to some pan­elists.

“The da­ta was in­con­sis­tent and there are some un­knowns that don’t make sense with the ra­tio­nale I heard,” said Joseph O’Brien, chief of Mass­a­chu­setts-based Na­tion­al Sco­l­io­sis Foun­da­tion, who en­dorsed posimir.”De­spite all these con­cerns, at the end of the day, we do have a need for opi­oid-spar­ing med­ica­tion,” he said, as cit­ed by Reuters.

Pan­elists against ap­proval ex­pressed their un­ease with posimir’s ef­fi­ca­cy, with some sug­gest­ing the ther­a­py’s du­ra­tion of ac­tion was lim­it­ed to 12 to 24 hours, echo­ing the FDA staff re­view is­sued on Tues­day. Con­cerns about safe­ty lin­gered with pan­elists on ei­ther side of the vote, and some sug­gest­ed ad­di­tion­al stud­ies were war­rant­ed to demon­strate res­cue in the event of ac­ci­den­tal in­tra­venous ad­min­is­tra­tion.

A 50/50 split vote is rare. Last year, a pill for pa­tients with the less com­mon type 1 di­a­betes, who pro­duce no in­sulin, was the sub­ject of an atyp­i­cal hung ju­ry vote at an FDA pan­el. Ex­perts were di­vid­ed even­ly over whether the life-threat­en­ing risk of di­a­bet­ic ke­toaci­do­sis as­so­ci­at­ed with the drug, so­tagliflozin, off­set its ben­e­fit — the FDA even­tu­al­ly re­ject­ed the di­a­betes ther­a­py.

Some pan­elists de­lib­er­at­ing on posimir seemed more open to con­sid­er­ing the ther­a­py’s da­ta as ev­i­dence of opi­oid-spar­ing com­pared to a No­vem­ber 2018 Ad­Com on opi­oid-spar­ing end­points, Cowen’s Boris Peak­er wrote in a note, which drew com­par­isons be­tween posimir and two oth­er bupi­va­caine painkillers: HTX-011 from Heron $HRTX and Ex­par­el from Paci­ra $PCRX.

“De­spite the ques­tion­able da­ta, the ‘yes’ votes were pri­mar­i­ly dri­ven by the time to opi­oid res­cue da­ta,” Peak­er wrote. “If time to opi­oid res­cue does be­come a sig­nif­i­cant end­point, HRTX’s da­ta ap­pears to be stronger than PCRX in cross-tri­al com­par­i­son. As such, we see this as an­oth­er op­por­tu­ni­ty for HTX-011 dif­fer­en­ti­a­tion vs. Ex­par­el.”

Paci­ra’s J&J-part­nered, long-act­ing post-op bupi­va­caine painkiller Ex­par­el gen­er­at­ed net sales of about $331 mil­lion in 2018. Heron’s HTX-011 — a for­mu­la­tion of bupi­va­caine and the non-steroidal an­ti-in­flam­ma­to­ry drug (NSAID) meloxi­cam — re­ceived an un­ex­pect­ed re­jec­tion due to man­u­fac­tur­ing con­cerns last year, but is on track to se­cure ap­proval by March.

Ear­li­er in the week, af­ter an FDA ad­vi­so­ry com­mit­tee vot­ed unan­i­mous­ly against Nek­tar Ther­a­peu­tics opi­oid painkiller — a for­mu­la­tion not en­gi­neered to fa­cil­i­tate abuse de­ter­rence from phys­i­cal ma­nip­u­la­tion — the com­pa­ny aban­doned the drug.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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CDC’s Robert Redford, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.

Laura Shawver (Silverback Therapeutics)

Fol­low­ing a hefty Se­ries B, Sil­ver­back Ther­a­peu­tics quick­ly pulls in $85M for 'an im­por­tant growth phase'

Months after reeling in a $78 million Series B round, Silverback Therapeutics has hooked an even larger Series C.

The Seattle-based company announced Wednesday that it netted $85 million from a slate of new and previous investors. The quick boost could be a sign that an IPO is on the way.

In an email, Silverback CEO Laura Shawver told me she was “not able to provide any additional comments about Silverback” beyond what was shared in the company’s news release. In the prepared statement, she said the company is at “an important growth phase.”

Covid-19 roundup: Op­er­a­tion Warp Speed's 7th vac­cine is live at­ten­u­at­ed; Small biotech touts big suc­cess where gi­ants have failed

Operation Warp Speed is stacking its vaccine portfolio with a “TBD” new candidate: a live attenuated vaccine that can be administered in a single dose, potentially as an oral formulation rather than an injection.

Sound familiar?

That could be because the unannounced candidate appears to match the profile of an inoculation being developed by Merck, according to Bloomberg, which first reported the development based on a presentation by Moncef Slaoui.

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On­ly five months af­ter a Se­ries A launch, Taysha goes pub­lic with $157M IPO

As has been the trend in 2020, Taysha Gene Therapies has become the latest biotech to make a quick ascent from a small, privately-funded company to enjoying its very own Nasdaq ticker.

The Dallas-based biotech raised $157 million for its IPO after pricing shares at $20 apiece Thursday, the high-point of its expected range. Initially pegging $100 million in financing, Taysha offered a little less than 8 million shares and will trade under the $TSHA symbol.

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CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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