Charles Nichols, LSU School of Medicine

Could psy­che­delics tack­le the obe­si­ty cri­sis? A long­time re­searcher in the field says his lat­est mouse study sug­gests po­ten­tial

Psy­che­delics have ex­pe­ri­enced a re­nais­sance in re­cent years amid a tor­rent of pre­clin­i­cal and clin­i­cal re­search sug­gest­ing it might pro­vide a path to treat mood dis­or­ders con­ven­tion­al reme­dies have on­ly scraped at. Now a pre­clin­i­cal tri­al from a young biotech sug­gests at least one psy­che­del­ic com­pound has ef­fects be­yond the mind, and — if you be­lieve the still very, very ear­ly hype — could pro­vide the first sin­gle rem­e­dy for some of the main com­pli­ca­tions of obe­si­ty.

A study in mice fund­ed by Eleu­sis and pub­lished in Sci­en­tif­ic Re­ports found a long-known drug called (R)-DOI could be used to treat car­dio­vas­cu­lar dis­ease, re­duc­ing in­flam­ma­tion in the aor­ta, de­creas­ing over­all and HDL cho­les­terol lev­els, and po­ten­tial­ly curb­ing di­a­betes by in­creas­ing glu­cose tol­er­ance.

Lead au­thor Charles Nichols says di­a­betes and high cho­les­terol, though of­ten re­sults of the same un­der­ly­ing con­di­tion, re­quire sep­a­rate drugs and a re­strict­ed di­et.

“This mod­el that treats car­dio­vas­cu­lar dis­ease and meta­bol­ic dis­ease — it’s all-en­com­pass­ing,” Nichols, a pro­fes­sor of phar­ma­col­o­gy at LSU, told End­points News. “Trans­lat­ed in­to the clin­ic in hu­mans, it would be as if some­one was obese, had di­a­betes, had high cho­les­terol, and was able to take a low dose of this drug at a sub-be­hav­ioral lev­el and re­al­ly treat sev­er­al dif­fer­ent as­pects of the com­pli­ca­tions of be­ing obese.”

They’re bold words, though al­most mut­ed in a psy­che­del­ic field brim­ming with hype. Re­searchers have called the re­sults of some psy­chi­atric stud­ies “mind-blow­ing” as clin­i­cal tri­als hint at the pow­er of psilo­cy­bin (the chem­i­cal in mag­ic mush­rooms) to al­le­vi­ate de­pres­sion and MD­MA to re­lieve PTSD.

David Nichols Pur­due

The no­tion that the same class of drugs might have oth­er phys­i­o­log­i­cal and specif­i­cal­ly an­ti-in­flam­ma­to­ry ef­fects is new­er. Nichols, the son of long­time psy­che­del­ic re­search pro­po­nent David Nichols, un­der­stands the rhetoric can get rosy but points out that the tri­al was tar­get­ed. They test­ed DOI in oth­er types of tis­sue and when it had lit­tle ef­fect, fo­cused on vas­cu­lar in­di­ca­tions.

“This is not a com­plete panacea,” said Nichols, who ear­li­er tout­ed his an­i­mal stud­ies in­di­cat­ing DOI’s po­ten­tial in asth­ma.

Nichols dis­cov­ered that sero­tonin 5-HT2A re­cep­tor ag­o­nists, fol­low­ing a well-un­der­stood path­way psy­che­delics act on, can re­duce in­flam­ma­tion by ac­ci­dent in his LSU lab in 2008. Lat­er, he got a cold call from Shlo­mi Raz, a for­mer Wall Street ex­ec­u­tive who went on to get a mas­ter’s in psy­chol­o­gy at NYU.

Eleu­sis launched in 2013 with a mis­sion, Raz told End­points, of ex­plor­ing the broad pos­si­bil­i­ties for these ag­o­nists, with their work so far rang­ing from a tri­al on the ef­fects of ‘mi­cro-dos­ing’ LSD on time per­cep­tion to fil­ing a patent for the treat­ment of Alzheimer’s with LSD. Nichols has pub­lished sev­er­al pre­vi­ous stud­ies on psy­che­delics and an­ti-in­flam­ma­to­ries, but this was no­table in its abil­i­ty to on­ramp in­to clin­i­cal tri­als.

Raz be­lieves what is com­mon­ly called psy­che­delics have a broad ar­ray of im­pacts be­yond their “psy­che­del­ic” func­tion. He says he has peer-re­viewed re­search com­ing soon that will help bol­ster that claim, and that the cen­tral ques­tion is how to un­lock those ef­fects with­out trig­ger­ing the psy­cho­log­i­cal im­pact.

“If you think of it as an ice­berg,” Raz said, “maybe the tip of the ice­berg is the psy­chi­atrics and the part be­low the sur­face is not psy­chi­atric.”

The vas­cu­lar study showed phys­i­o­log­i­cal with­out any psy­cho­log­i­cal ef­fects (mice giv­en a psy­che­del­ic can some­times show be­hav­ior con­sis­tent with psy­chosis). The re­searchers fat­tened up mice on the “West­ern di­et” for four months and at in­ter­vals ad­min­is­tered DOI to one group and saline to a con­trol.

They found that vas­cu­lar in­flam­ma­tion was low­er in the DOI, as they an­tic­i­pat­ed. They hadn’t an­tic­i­pat­ed that cho­les­terol would be down and glu­cose tol­er­ance up, and they’re still not sure why.

Nichols, though, said the study was trans­lat­able to a clin­i­cal tri­al, and he was hope­ful there would be a drug with­in 10 to 20 years. Reg­u­la­tion, more than the sci­ence, was the bar­ri­er. Raz was mum about what’s next, both in terms of oth­er ap­pli­ca­tions and in busi­ness mod­el, but he left one clue:

“I can tell you it’s not a pill,” he said, “at first.”

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?

Image: Shutterstock

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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Mer­ck scraps their $425M Covid-19 drug in lat­est pan­dem­ic set­back

Seven months after paying $425 million cash to acquire it, Merck is scrapping a Covid-19 drug they hoped could provide one of the only treatments for severe hospitalized patients.

Merck’s decision comes after they faced significant and unexpected regulatory delays in getting the drug, known as MK-7110 or CD24Fc, across the finish line. The Big Pharma licensed the drug under the belief that it had already shown sufficient benefit in severe patients and they could help scale it up far faster than OncoImmune, its former owner, could. But in February, the company reported that the FDA insisted Merck run a new trial before seeking authorization.

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Severin Schwan, Roche CEO (Georgios Kefalas/Keystone via AP Images)

Look­ing to ce­ment its lead in packed MS mar­ket, Roche's Ocre­vus un­corks new da­ta in ear­ly-stage pa­tients

Among a positively jam-packed multiple sclerosis market, Roche’s Ocrevus has managed to stand out for what the Swiss drugmaker is calling the most successful launch in its long history. But in order to press its advantage, Ocrevus is looking to earlier-stage patients, and new interim data should help build its case there.

After 48 weeks on Roche’s Ocrevus, 85% of newly diagnosed primary progressing or relapsing MS patients without a history of disease modifying therapy posted no disease activity, including disease progression or relapse, according to interim data set to be presented this weekend at the virtual American Academy of Neurology meeting.

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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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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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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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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