Re­call re­port: AvKARE some­how mixed its an­ti­de­pres­sant and erec­tile dys­func­tion meds; Tor­rent pulls throm­bo­cy­to­sis drug

Any num­ber of is­sues can lead to an FDA re­call, but here’s one you don’t see every day: A third-par­ty man­u­fac­tur­er for Ten­nessee-based AvKARE ap­par­ent­ly mixed an an­ti­de­pres­sant and erec­tile dys­func­tion med in­to the same pack­ag­ing, cre­at­ing a po­tent — if ac­ci­den­tal — mix for pa­tients.

The FDA on Wednes­day an­nounced AvKARE launched a vol­un­tary re­call of one lot each of gener­ic tra­zodone, the an­ti­de­pres­sant, and silde­nafil, an erec­tile dys­func­tion med­ica­tion, af­ter dis­cov­er­ing the two med­ica­tions had been mixed to­geth­er.

While no pa­tient is­sues have been re­port­ed from the re­called prod­ucts, in­gest­ing the wrong drug could have po­ten­tial­ly se­ri­ous com­pli­ca­tions — par­tic­u­lar­ly with re­gards to silde­nafil, the FDA said. The drug could in­ter­act neg­a­tive­ly with ni­trates found in blood and low­er blood pres­sure to dan­ger­ous lev­els — po­ten­tial­ly prob­lem­at­ic as con­sumers with di­a­betes, high blood pres­sure or heart dis­ease more of­ten take ni­trates, and those in the age de­mo­graph­ic with such dis­eases are typ­i­cal­ly more like­ly to take med­ica­tion for erec­tile dys­func­tion.

Un­in­tend­ed in­take of tra­zodone, the FDA said, could re­sult in drowsi­ness, se­da­tion, dizzi­ness or blurred vi­sion, of more con­cern to el­der­ly pa­tients due to a pos­si­ble in­creased risk of falling and im­paired dri­ving.

The af­fect­ed lot of silde­nafil 100 mg tablets in­clud­ed 100 bot­tles with an ex­pi­ra­tion date of March 2022, while the af­fect­ed lot of Tra­zodone 100 mg tablets in­clud­ed 1,000 bot­tles with an ex­pi­ra­tion date of June 2022. The prod­ucts were dis­trib­uted to AvKARE dis­trib­u­tors and whole­salers be­fore be­ing fur­ther dis­trib­uted across the coun­try.

Al­so this week, the FDA an­nounced a vol­un­tary na­tion­wide re­call of one lot of Tor­rent Phar­ma­ceu­ti­cals’ ana­gre­lide cap­sules, USP.

The drug, used to treat a blood cell dis­or­der that el­e­vates platelet counts called throm­bo­cy­to­sis, failed a dis­so­lu­tion test dur­ing reg­u­lar qual­i­ty test­ing. This can lead to a slow­er rate and lev­el of drug re­lease in­to the body, which could have po­ten­tial­ly life-threat­en­ing ef­fects for pa­tients with more se­ri­ous cas­es of the dis­or­der, the FDA said.

Pa­tients tak­ing ana­gre­lide are asked to speak with their pre­scrib­ing physi­cian be­fore im­me­di­ate­ly stop­ping tak­ing the med­ica­tion, the FDA said, as the risk of harm in do­ing so may be high­er than the dis­so­lu­tion is­sue.

Tor­rent said the lot of faulty dis­so­lu­tion tablets was doled out in the US na­tion­wide to its whole­sale dis­trib­u­tor and re­tail cus­tomers. It was not clear whether ad­verse ef­fects from the re­called med­ica­tion had been re­port­ed.

The re­call is the lat­est in a string of is­sues for Tor­rent, based in Ahmed­abad, In­dia. Just since ear­ly 2019, the com­pa­ny has is­sued 10 FDA re­calls of var­i­ous drugs due to is­sues rang­ing from trace amounts of car­cino­gens dis­cov­ered in drug el­e­ments, steril­i­ty prob­lems and im­pu­ri­ties dis­cov­ered through qual­i­ty test­ing.

In May 2019, the FDA al­so dis­cov­ered test­ing is­sues at a Tor­rent pro­duc­tion plant in which the plant rou­tine­ly re­port­ed prod­ucts as out of spec­i­fi­ca­tion but fre­quent­ly shipped the drugs to the US any­way.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Chris Gibson (Photo By Vaughn Ridley/Sportsfile for Web Summit via Getty Images)

Re­cur­sion founders gin for­tunes as IPO back­ers show­er $436M on one of the biggest boasts in AI -- based on some very small deals

In the AI drug development world, boasting often comes with the territory. Yet few can rival Recursion when it comes to claiming the lead role in what company execs like to call the industrialization of drug development, with promises of continued exponential growth in the number of drugs it has in the pipeline.

On Friday, the Salt Lake City-based biotech translated its unicorn-sized boasts into a killer IPO, pricing more than 24 million shares at the high end of its range and bringing in $436 million — with a large chunk of that promised by some deep-pocket backers.

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Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Covid-19 vac­cine halt drags on, an FDA ap­point­ment at long last, the great CRO con­sol­i­da­tion, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Conference season is upon us, and while we’d much prefer to be wandering down the hallways and presentation rooms in person, the team is ready to cover the most consequential data coming out of these scientific meetings. Get in touch early if you have news to share.

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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As­traZeneca-Alex­ion merg­er slides through FTC re­view af­ter sup­posed M&A crack­down pos­es no bar­ri­ers

The AstraZeneca-Alexion megamerger received a good sign Friday, despite warning signs of the tides turning against large M&A pharma deals.

US regulators at the FTC have cleared the acquisition for approval, AstraZeneca announced, all but signing off on the deal to go through once it officially closes in the third quarter. AstraZeneca originally said it was planning to buy out Alexion back in December for $39 billion.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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David Stack, Pacira Biosciences CEO

In high­ly un­usu­al move, Paci­ra sues med­ical jour­nal for li­bel over its non-opi­oid painkiller

A New Jersey biotech whose only approved drug is used as a painkiller after surgeries is suing a scientific journal, its editors and a handful of authors for libel after the publication printed numerous papers and editorials that the company says discredited the drug.

Pacira Biosciences filed the complaint against the American Society of Anesthesiologists in the US District Court for New Jersey on Wednesday afternoon. A February issue of the group’s journal Anesthesiology printed three articles and other content full of “bias” that “seriously disparaged” the drug Exparel, Pacira claimed.