Psy­che­del­ic re­search gains mo­men­tum, as ear­ly tri­al sug­gests mi­cro-dos­ing LSD is safe

Psy­che­delics have been long ne­glect­ed as the sub­ject of vig­or­ous sci­en­tif­ic re­search af­ter gov­ern­ments brand­ed them as il­le­gal he­do­nis­tic com­pounds with no ther­a­peu­tic po­ten­tial. But in re­cent years, de­spite tricky reg­u­la­tions, a resur­gence of in­ter­est from re­searchers has cul­mi­nat­ed in an FDA ap­proved ke­t­a­mine-de­rived de­pres­sion treat­ment, clin­i­cal tri­als test­ing the po­ten­tial of psilo­cy­bin in ‘mag­ic mush­rooms,’ and the set­ting up of a psy­che­del­ic re­search cen­ter at Johns Hop­kins.

The col­or­less, odor­less and taste­less drug, ly­ser­gic acid di­ethy­lamide (LSD) — or acid, as it is fond­ly known — is part of this re­search re­nais­sance. On Wednes­day, a small pri­vate­ly held com­pa­ny — Eleu­sis Ben­e­fit Cor­po­ra­tion — un­veiled da­ta from an ear­ly study in healthy old­er vol­un­teers that test­ed its mi­cro-dos­ing ap­proach with LSD. And if it all goes ac­cord­ing to plan — nev­er a sure thing in biotech — they’ve got plans to tar­get Alzheimer’s with the ap­proach.

Neilo­u­far Fam­i­ly

In the study, 48 vol­un­teers (mean age = 62.9 years) re­ceived ei­ther 5 μg, 10 μg, or 20 μg of LSD, or place­bo  — ad­min­is­tered in wa­ter — every four days in six ses­sions. Over­all, the LSD was well tol­er­at­ed, and the fre­quen­cy of ad­verse events was no high­er than the place­bo, the com­pa­ny said, while claim­ing this is the first ever pub­li­ca­tion of clin­i­cal study da­ta on mi­cro-dosed LSD.

PK da­ta showed that the half-life of the LSD dos­es was short. “So at 12 hours post-dose, there was no drug in the blood at any of the dos­es,” Neilo­u­far Fam­i­ly, the tri­al’s lead in­ves­ti­ga­tor, told End­points News. “And there al­so wasn’t any drug in the blood at base­line on the sixth dose.”

The da­ta sup­port fur­ther clin­i­cal de­vel­op­ment of LSD, whose psy­choac­tiv­i­ty is un­der­stood to be me­di­at­ed pri­mar­i­ly through the 5-HT2A re­cep­tor, Eleu­sis said. The com­pa­ny even plans to de­vel­op the drug to treat and pre­vent Alzheimer’s dis­ease, a field lit­tered with fail­ure and a pauci­ty of promis­ing ther­a­peu­tics in the late-stage pipeline.

But the brim­ming en­thu­si­asm comes with a healthy dose of skep­ti­cism. Crit­ics wor­ry that the bur­geon­ing psy­che­del­ic re­search could in­cen­tivize un­bri­dled use of non-phar­ma­ceu­ti­cal ver­sions of these drugs and that clin­i­cal tri­al da­ta could be cloud­ed by the fact that place­bo-con­trolled stud­ies are not nec­es­sar­i­ly dou­ble-blind­ed, be­cause it is far too easy to de­ter­mine which group of pa­tients have been giv­en a place­bo.

“The one thing that we did ex­pect — but is still re­mark­able — is the high place­bo re­sponse,” Fam­i­ly said. “Peo­ple were re­port­ing per­cep­tions of psy­choac­tive ef­fects, when lat­er on we found out they were on place­bo…but in any case, any per­cep­tions of psy­choac­tive ef­fects were very mild and they sub­sided by the end of the day, both in the ac­tive dose groups and the place­bo groups.”

Eleu­sis has a plan to hedge its Alzheimer’s bet, and to deal with the pesky prob­lem of di­ver­sion.

Be­fore div­ing in­to a Phase II ef­fi­ca­cy study in Alzheimer’s, the com­pa­ny is plan­ning an ear­ly-stage study with a com­pound — a “not-so-psy­che­del­ic” psy­che­del­ic sero­tonin 5-HT2A ag­o­nist — in oph­thal­mol­o­gy. At the mo­ment, the eye drug is at the pre­clin­i­cal stage of de­vel­op­ment.

Shlo­mi Raz

The Phase I tri­al, which is ex­pect­ed to kick off in ear­ly 2021, will pro­vide a key mech­a­nis­tic in­sight in­to how psy­che­delics could pre­vent neu­rode­gen­er­a­tion as­so­ci­at­ed with in­flam­ma­tion, Eleu­sis chief Shlo­mi Raz told End­points.

“The eye is a win­dow to the soul but al­so to the brain,” he said.”The reti­na, in par­tic­u­lar, gives us a very neat way of as­sess­ing how psy­che­delics could po­ten­tial­ly man­age neu­ro­pro­tec­tion, neu­roin­flam­ma­tion and pro­vides us a cost-ef­fec­tive proof-of-con­cept be­fore go­ing in­to — by all mea­sures —what seems to be the most ex­pen­sive type of clin­i­cal tri­al around, which is in Alzheimer’s dis­ease.”

The hope is to de­vel­op an LSD com­pound for ther­a­peu­tic use that can be used in the out­pa­tient set­ting, but psy­choac­tiv­i­ty is a risk that must be mon­i­tored, he said. The com­pa­ny says it is de­vel­op­ing a non­in­va­sive safe­ty mon­i­tor­ing tech­nol­o­gy that will be used in its clin­i­cal tri­als, and if the com­pound is ap­proved, for pa­tient use.

“In all cas­es, there’s a cal­cu­lus of safe­ty, ver­sus un­met need, and clin­i­cal util­i­ty,” he said.  “I think in the case of Alzheimer’s dis­ease, should we demon­strate that LSD in fact, is ef­fec­tive in slow­ing or halt­ing the pro­gres­sion of the dis­ease, then I think that there’s a clear jus­ti­fi­ca­tion for tak­ing that risk.”

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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