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.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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UP­DAT­ED: Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Covid-19 roundup: Af­ter promis­ing US its sum­mer sup­ply, Gilead in talks with EU over remde­sivir ac­cess; First in­haled remde­sivir study un­der­way

It wasn’t lost on European journalists or European doctors that the “amazing deal” the Trump Administration said it signed with Gilead to buy up remdesivir meant that they would have severely limited access to one of only two drugs proven to treat Covid-19. “This is the first major approved drug, and where is the mechanism for access?” Andrew Hill, a research fellow at Liverpool University, told The Guardian. “Once again we’re at the back of the queue.”

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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FDA bars the door — for now — against Mer­ck’s star can­cer drug af­ter Roche beat them to the punch

Merck has been handed a rare setback at the FDA.

After filing for the accelerated approval of a combination of their star PD-1 drug Keytruda with Eisai’s Lenvima as a first-line treatment for unresectable hepatocellular carcinoma, the FDA nixed the move, handing out a CRL because Roche beat them to the punch on the same indication by a matter of weeks.

According to Merck:

Ahead of the Prescription Drug User Fee Act action dates of Merck’s and Eisai’s applications, another combination therapy was approved based on a randomized, controlled trial that demonstrated overall survival. Consequently, the CRL stated that Merck’s and Eisai’s applications do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies for the treatment of unresectable or metastatic HCC with no prior systemic therapy for advanced disease. Since the applications for KEYNOTE-524/Study 116 no longer meet the criteria for accelerated approval, both companies plan to work with the FDA to take appropriate next steps, which include conducting a well-controlled clinical trial that demonstrates substantial evidence of effectiveness and the clinical benefit of the combination.

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Roger Tung, Concert Pharmaceuticals CEO (Concert)

Con­cert gets BTD for alope­cia drug, set­ting up a late-stage show­down with gi­ant ri­val Pfiz­er

Concert Pharmaceuticals’ path to developing a drug that treats alopecia areata has been bumpy, but the pharma company scored a win Wednesday.

The FDA granted Concert a Breakthrough Therapy Designation (BTD) for its oral Janus kinase inhibitor, named CTP-543, paving the way for a Phase III study of the drug to begin in the fourth quarter of 2020. The news follows positive Phase II results from last September, which saw the drug meet its primary endpoint in both 8 mg and 12 mg twice-daily doses.

Covid-19 roundup: Mod­er­na sticks to Ju­ly for its Phase III as ru­mors swirl; Fol­low­ing US lead, EU buys up Covid-19 treat­ments

The Phase III might be delayed from its original early July goal, but Moderna says it will still kick off the pivotal study for what could ultimately be the first Covid-19 vaccine before the end of the month.

A day after Reuters reported that squabbling between the Cambridge biotech and government regulators had held up the trial by about two weeks, Moderna released a statement saying that they had completed enrollment of their 650-person Phase II trial and were on track to begin Phase III by the end of the month. The protocol for that study, which is meant to prove whether or not the vaccine can prevent people from becoming sick, has been finalized, they said.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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GSK sets the stage for a toe-to-toe mar­ket show­down with Gilead­'s HIV cham­pi­on Tru­va­da

ViiV Healthcare and majority owner GlaxoSmithKline have cleared another important hurdle on a long-running quest to challenge Gilead’s dominance in preventative HIV treatments.

The final analysis of a new study shows the GSK subsidiary’s long-lasting injection, cabotegravir, proved 66% more effective in HIV prevention than Gilead’s breakthrough Truvada pill. And they now intend to carve away some of the blockbuster revenue that Gilead has enjoyed for years.