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.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

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Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

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Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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CEO Fred Aslan (Artiva)

NK cell ther­a­py play­er Arti­va makes some more noise, pulling in $120M Se­ries B less than a month af­ter Mer­ck deal

Not even one month after Big Pharma took notice of Artiva when Merck signed a collaboration worth nearly $2 billion in milestones, the off-the-shelf NK cell biotech already has its next big fundraise.

Artiva returns from the venture well Friday with a $120 million Series B round, money they will use to get their first program into the clinic and to file INDs for another two candidates. The raise marks the latest development in a rapidly expanding footprint for Artiva, which, in addition to the Merck deal last month, has now raised almost $200 million since its Series A last June.

The path to NASH: un­der­stand­ing the role of se­vere obe­si­ty in a com­plex, mul­ti-sys­tem dis­ease

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We often think a person’s transition from a healthy to a diseased state is binary. But that’s often not the case. In reality, the onset of a disease is not something that occurs overnight, and the majority lie on a continuum that is impacted by a multitude of factors. Some of these factors are in a patient’s control. Others are not.

This is the case in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), two of the most complex diseases that “live” on this proverbial continuum. The clinical onset of NAFLD — and ultimately NASH — is a complex process that is closely related to obesity, insulin resistance and impaired adipose tissue metabolism.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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