FDA staff high­lights neu­ro­log­i­cal safe­ty con­cerns with Durec­t's pain drug

Days af­ter sting­ing tri­al fail­ure forced the Cal­i­for­nia com­pa­ny to aban­don its pso­ri­a­sis pro­gram, FDA staff re­view­ers is­sued a re­view that high­light­ed the risk of neu­ro­log­i­cal side ef­fects with Durect Corp’s long-act­ing anes­thet­ic, posimir, for pa­tients with post-sur­gi­cal anal­ge­sia.

Posimir, an ex­tend­ed-re­lease for­mu­la­tion of the ap­proved anes­thet­ic — bupi­va­caine — has a check­ered past. The com­pa­ny, which orig­i­nal­ly part­nered with No­var­tis on the pro­gram, first sub­mit­ted an ap­pli­ca­tion to mar­ket the drug on the ba­sis of sev­en tri­als, in­clud­ing two piv­otal stud­ies in pa­tients un­der­go­ing her­nia re­pair and shoul­der surgery. The FDA spurned the ap­pli­ca­tion in 2014 over safe­ty con­cerns.

Durect then con­duct­ed an­oth­er study, di­vid­ed in­to two parts: a place­bo arm and a com­para­tor arm (bupi­va­caine). The com­para­tor arm was added at the be­hest of the FDA — and the com­pa­ny elect­ed to dis­con­tin­ue the place­bo arm. (The FDA said it con­sid­ered the two arms as two sep­a­rate stud­ies).

Ei­ther way, posimir failed to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence against the place­bo or bupi­va­caine in the tri­al, dubbed PER­SIST. Some safe­ty con­cerns, par­tic­u­lar­ly neu­ro­log­i­cal ad­verse events, al­so per­sist­ed, FDA staff not­ed in their re­view.

As not­ed in the 2014 com­plete re­sponse let­ter, FDA staff un­der­scored the high­er in­ci­dence of ner­vous sys­tem ad­verse events, such as som­no­lence, dizzi­ness, and dys­geu­sia in pa­tients giv­en posimir.

Al­though Durect pro­vid­ed a ra­tio­nale for the im­bal­ance in­di­cat­ing it was due to the var­ied meth­ods for ad­verse event col­lec­tion, FDA re­view­ers ap­peared un­con­vinced. “This rep­re­sents an­oth­er post-ac­tion analy­sis of da­ta con­duct­ed by the Ap­pli­cant in­stead of a prospec­tive un­bi­ased col­lec­tion of da­ta,” they wrote.

A pan­el of in­de­pen­dent ad­vi­sors is set to de­lib­er­ate on the drug on Thurs­day. The FDA typ­i­cal­ly fol­lows the pan­el’s rec­om­men­da­tions but is not ob­lig­at­ed to.

Stifel an­a­lysts, in a note ear­li­er this month, es­ti­mat­ed posimir has a mea­ger 30% shot at ap­proval in light of its dif­fi­cult reg­u­la­to­ry his­to­ry.

In 2014, the FDA re­ject­ed the drug, cit­ing a pletho­ra of safe­ty con­cerns in­clud­ing side-ef­fects re­lat­ed to the shoul­der joint and sur­round­ing tis­sues; the risk of bruis­ing, hematoma, pru­ri­tus among oth­ers; and a marked in­creased risk of neu­ro­log­i­cal ad­verse events.

Durect ap­pealed the de­ci­sion — and re­ceived an even more bru­tal re­sponse from the agency. “I be­lieve ef­fi­ca­cy is present with Posimir but it is mod­est and in­con­sis­tent across dif­fer­ent sur­gi­cal pro­ce­dures. My con­clu­sion on ef­fi­ca­cy pre­clude com­plete dis­missal of the safe­ty con­cerns raised by the Di­vi­sion,” wrote Mary Thanh Hai Parks, deputy di­rec­tor of the of­fice of drug eval­u­a­tion. Durect then con­duct­ed the PER­SIST study, hop­ing to quell the agency’s con­cerns.

Mean­while, in ear­ly Jan­u­ary, the com­pa­ny’s ex­per­i­men­tal DUR-928 failed a mid-stage plaque pso­ri­a­sis study. Last Ju­ly, Gilead in­ject­ed some con­fi­dence in­to the com­pa­ny’s HIV pro­gram, pay­ing $25 mil­lion up­front and promis­ing mil­lions more in mile­stone pay­ments to latch on­to that plat­form.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

FDA can­cels ODAC meet­ing this week to re­view two more dan­gling ac­cel­er­at­ed ap­provals — but won't ex­plain why

The FDA’s Oncologic Drugs Advisory Committee has decided to cancel a planned meeting on Thursday to discuss two cancer drugs that previously won accelerated approvals but failed to confirm clinical benefit in required follow-up trials or have taken a long time to finish those trials.

The FDA said in a statement that the meeting “is no longer needed” but did not offer further detail on why exactly it was canceled, telling Endpoints News to contact the companies. Attempts to contact both Secura Bio and Acrotech went unreturned. The companies may have decided to pull these treatments from the market, or they’ve come to new agreements with the agency on their confirmatory trials.

How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Mar­ket­ingRx roundup: Ab­b­Vie’s Hu­mi­ra TV turns fo­cus to HS skin con­di­tion; Sanofi amps par­ent­ing pol­i­cy

After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.