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.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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No stranger to gene ther­a­py woes, Astel­las runs in­to an­oth­er safe­ty-re­lat­ed clin­i­cal hold

Astellas Pharma, which has been at the forefront of uncovering the risks associated with gene therapies delivered by adeno-associated viruses, must take another safety alarm head-on.

The FDA has slapped a clinical hold on Astellas’ Phase I/II trial of a gene therapy candidate for late-onset Pompe disease, after investigators flagged a serious case of peripheral sensory neuropathy.

It marks the latest in a streak of setbacks Astellas has encountered since making a splashy entry into the gene therapy space with its $3 billion buyout of Audentes. But the lead program, AT132 for the treatment of X-linked myotubular myopathy (XLMTM), had to be halted more than once after a total of four patients died in the trial — and the scientific community still doesn’t have all the answers of what caused the deaths.

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Albert Bourla, Pfizer CEO (Gian Ehrenzeller/Keystone via AP Images)

Up­dat­ing the Covid-19 vac­cine: FDA of­fers a qual­i­fied thumbs-up ahead of ad­comm

The FDA’s adcomm of outside vaccine experts will meet tomorrow to discuss how to protect the US from a likely coming wave of Omicron cases in the fall and winter, and whether to deploy vaccines that specifically target the Omicron variant.

While the data so far are limited, the FDA sounded an upbeat tone in the briefing documents on Pfizer/BioNTech’s candidates, released this weekend ahead of the VRBPAC meeting.

Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

As court case looms, Bris­tol My­ers touts la­bel ex­pan­sion for Breyanzi

As Bristol Myers Squibb braces for a court battle over a costly delay — at least for Celgene shareholders — for its CAR-T lymphoma treatment Breyanzi, the pharma giant is touting a label expansion in the second-line setting.

Breyanzi, also known as liso-cel, snagged a win on Friday in adults with large B-cell lymphoma (LBCL) who: don’t respond to chemotherapy, or relapse within 12 months; don’t respond or relapse after 12 months; or are not eligible for hematopoietic stem cell transplant after chemo due to their age or comorbidities.

Deborah Dunsire, Lundbeck CEO

Af­ter a 5-year re­peat PhI­II so­journ, Lund­beck and Ot­su­ka say they're fi­nal­ly ready to pur­sue OK to use Rex­ul­ti against Alzheimer's ag­i­ta­tion

Five years after Lundbeck and their longtime collaborators at Otsuka turned up a mixed set of Phase III data for Rexulti as a treatment for Alzheimer’s dementia-related agitation, they’ve come through with a new pivotal trial success they believe will finally put them on the road to an approval at the FDA. And if they’re right, some analysts believe they’re a short step away from adding more than $500 million in annual sales for the drug, already approved in depression and schizophrenia.

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A Mer­ck part­ner is sucked in­to the fi­nan­cial quag­mire as key lender calls in a note

Another biotech standing on shaky financial legs has fallen victim to the bears.

Merck partner 4D Pharma has reported that a key lender, Oxford Finance, shoved the UK company into administration after calling in a $14 million loan they couldn’t immediately make good on. Trading in their stock was halted with a market cap that had fallen to a mere £30 million.

“Despite the very difficult prevailing market conditions,” 4D reported on Friday, the biotech had been making progress on finding some new financing and turned to Oxford with an alternative late on Thursday and then again Friday morning.

Members of the G7 from left to right: Prime Minister of Italy Mario Draghi, European Commission President Ursula von der Leyen, President Joe Biden, German Chancellor Olaf Scholz, British Prime Minister Boris Johnson, Canadian Prime Minister Justin Trudeau, Prime Minister of Japan Fumio Kishida, French President Emmanuel Macron and European Council President Charles Michel (AP Photo/Susan Walsh)

Biden and G7 na­tions of­fer funds for vac­cine and med­ical prod­uct man­u­fac­tur­ing project in Sene­gal

Amidst recently broader vaccine manufacturing initiatives from the EU and European companies, the G7 summit in the mountains of Bavaria has brought about some positive news for closing vaccine and medical product manufacturing gaps around the globe.

According to a statement from the White House, the G7 leaders have formally launched the partnership for global infrastructure, PGII. The effort will aim to mobilize hundreds of billions of dollars to deliver infrastructure projects in several sectors including the medical and pharmaceutical manufacturing space.