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.

Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Michel Vounatsos, Biogen CEO (Biogen via YouTube)

Damn the crit­ics, Bio­gen CEO Vounatsos or­ders full speed ahead on prep­ping a con­tro­ver­sial ad­u­canum­ab launch as FDA de­ci­sion looms

Right now one of the most interesting parlor games on Wall Street is offering odds on Biogen’s chances of getting an FDA OK on their controversial Alzheimer’s drug aducanumab.

For most objective players, it looks about like a coin toss, maybe a little worse than 50/50, as the Street balances the bull case of a full, mega blockbuster approval, a restricted approval or a disastrous order to go back to the clinic and mount a new Phase III. That last option was clearly the guidance most of the outside experts in the panel review offered the agency, as the industry is still puzzling out the question of whether or not the FDA is getting tougher in its oversight of drug development.

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Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Why re­mote drug man­u­fac­tur­ing eval­u­a­tions won't re­al­ly re­duce FDA's back­log of in­spec­tions

For the first several months of the pandemic last spring, the FDA continued to plow through its user fee-enabled work on new drug and biologic applications, meeting nearly all of its goal dates.

But by last fall and into the winter, complete response letters and other delays began arriving in companies’ mailboxes as the agency struggled to catch up to a growing backlog of both domestic and foreign drug manufacturing inspections.

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Bay­er plots a ma­jor facelift at Berke­ley cam­pus, un­cork­ing a 30-year, $1.2B plan to dri­ve cell and gene ther­a­pies

Bayer first set roots in Berkeley back in 1974, when it was still operating as Miles Labs. The site has pumped out three hemophilia A treatments for distribution worldwide; but now, as the pharma continues its cell and gene therapy push, it has something bigger in mind.

Bayer is planning a 30-year revamp at the campus, which includes 918,000 square feet in new buildings and double the jobs, according to a report by the Bay Area Council Economic Institute.

LLS backs 5 new can­cer drug projects with up to $50M; Trodelvy con­tin­ues to im­press with more TNBC da­ta

The Leukemia and Lymphoma Society has tapped 5 new early-stage projects to back with up to $10 million each in fresh investments. The 5 biotechs are:

— Caribou, headed by Rachel Haurwitz and co-founded by Jennifer Doudna, is working on next-gen, off-the-shelf CAR-Ts to replace the patient-derived cells now in use.

— The LLS supported NexImmune’s IPO, helping fund its work on nanoparticles that can gin up an immune response directed at cancer cells. The biotech has 2 projects now in Phase I trials.