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.”

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Patrik Jonsson, the president of Lilly Bio-Medicines

Who knew? Der­mi­ra’s board kept watch as its stock price tracked Eli Lil­ly’s se­cret bid­ding on a $1.1B buy­out

In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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Ab­b­Vie do­nates $1M+ of the HIV drug that Chi­na is now rec­om­mend­ing for coro­n­avirus treat­ment

AbbVie is donating more than $1 million worth of an HIV drug to help combat the fast-spreading coronavirus outbreak in China, the company announced on Friday.

China’s National Health Commission has suggested Aluvia, a pill containing lopinavir and ritonavir, as one of two possible treatments for the symptoms of the virus currently known as 2019-nCoV in the absence of effective antiviral medications. The other part is nebulized alpha-interferon.

Ab­b­Vie and Al­ler­gan di­vesti­tures are in, and an old As­traZeneca drug comes home

When AbbVie announced their $63-billion Allergan acquisition last year, executives acknowledged the two companies would have to divest some drugs to satisfy regulators. The two main assets in discussion have now been sold off – and one of them is coming home.

AstraZeneca will acquire brazikumab, Allergan’s late-stage IL-23 candidate for Crohn’s disease and ulcerative colitis. The drug was originally developed by AstraZeneca’s defunct subsidiary MedImmune, in collaboration with Amgen. Allergan licensed it for $250 million upfront and $1.27 billion in milestones.

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As­traZeneca makes case for use of blood thin­ner Bril­in­ta in stroke pa­tients

AstraZeneca’s extravagant projections for its clot fighter Brilinta may have fizzled in the face of underwhelming trial data — but a new pivotal study is set to expand its use substantially.

On Monday, the British drugmaker said the drug, when taken in conjunction with aspirin, induced a statistically significant reduction in the risk of the primary composite endpoint of stroke and death, compared to aspirin alone, in 11,000 patients that have suffered minor acute ischaemic stroke or a high-risk transient ischemic attack (TIA).

Samantha Truex (file photo)

Bruce Booth and Saman­tha Truex's lat­est ven­ture aims just above Hu­mi­ra

In 2000, about a year after the first trial data on Humira came out, a Japanese team identified a new gene that appeared to prevent GI cancer in mice: gasdermin, they called it, after the particular proteins it expressed.

Over the next decade-and-a-half, researchers found five more genes in the same family – often identified as gasdermin A, B, C, D, E and F – and yet their purpose baffled scientists. Mutations in appeared to make mice bald (alopecia), but deleting it had no effect. Mutations in F and A were linked to deafness. Mutant E caused human cells to self-destruct.

“The exact biological function of these proteins remained unknown for more than 15 years,” three of the field’s top researchers wrote in a  Nature review in November.

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FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back — this time flunk­ing fu­til­i­ty test — as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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