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.”

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

Laurent Fischer, Adverum CEO

Ad­verum faces murky fu­ture af­ter re­view turns up deep­er safe­ty is­sues for gene ther­a­py

Three months after revealing that a patient lost significant vision in one eye after receiving its experimental gene therapy, Adverum announced it found the safety issues were more widespread: Five of 12 patients who received a high dose of the therapy saw “similar clinically-relevant events.”

Three required surgery on their treated eye. And all 12 are being recommended “aggressive immunomodulatory treatments” to prevent further injury.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Bio­gen has a shaky end to H1 with a $542M write-off adding to its woes — but an­a­lysts see big rev­enue ahead for Aduhelm

All eyes at Biogen’s Q2 earnings call Thursday were on Aduhelm, but investors also got a glimpse of what Biogen would have faced had the FDA not opted to approve their controversial Alzheimer’s drug.

That glimpse, revealing a combination of declining sales, growing competition and failed medicines, underscores the stakes of the big biotech’s Aduhelm efforts, as execs punch back at the criticism they’ve engendered in the political and medical world and vigorously pushes its sales staff to roll out the drug as fast as possible.

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Mol­e­c­u­lar Di­ag­nos­tics Can Trans­form Can­cer Care. Let’s Make It Hap­pen.

Like so many people around the world, my life has been profoundly shaped by cancer. Those personal experiences, along with a deep love of clinical laboratory science and a passion to apply the power of genomics in medicine, motivated me to launch a company that would improve cancer care through better diagnostics. Thirteen years later, I am proud that we are delivering more accurate information at multiple points along the patient journey, with a focus on eight of the 10 cancers that are most commonly diagnosed in the United States.