Can CBD tem­per Parkin­son's-re­lat­ed psy­chosis? UK re­searchers will look for an­swers in PhII study

Cannabid­i­ol (CBD), the cannabi­noid com­pound found in the cannabis plant, has been tried and test­ed in pa­tients with rare forms of epilep­sy, in­spir­ing the ap­proval of GW Phar­ma’s $GW­PH land­mark plant-de­rived Epid­i­olex. Its resur­gence in re­search — and its ubiq­ui­tous pres­ence in oils, creams, and gum­my bears — is on the ba­sis that it is not ad­dic­tive, like its in­tox­i­cat­ing cousin THC, and re­tains the ther­a­peu­tic po­ten­tial for a plant that was once tout­ed as a cure-all in In­dia. Re­searchers at King’s Col­lege Lon­don have been study­ing the ef­fect of CBD on psy­chosis, and on Mon­day sig­naled they are prep­ping to be­gin a large-scale Phase II tri­al in pa­tients with Parkin­son’s-re­lat­ed psy­chosis, char­ac­ter­ized by hal­lu­ci­na­tions and delu­sions.

The re­search team, led by Pro­fes­sor Sag­nik Bhat­tacharyya from the In­sti­tute of Psy­chi­a­try, Psy­chol­o­gy & Neu­ro­science, will as­sess the safe­ty and ef­fec­tive­ness of CBD by track­ing psy­chot­ic, mo­tor and non-mo­tor symp­toms, along­side brain imag­ing.

The emer­gence of dopamine D2 re­cep­tor an­tag­o­nists in the 1950s trans­formed the treat­ment of psy­chot­ic dis­or­ders — and they per­sist as one of the main tools in the treat­ment ar­se­nal for psy­chosis. How­ev­er, tra­di­tion­al an­tipsy­chotics car­ry a litany of side ef­fects and a sig­nif­i­cant pro­por­tion of pa­tients do not de­rive ad­e­quate ben­e­fit from the class of drugs.

CBD casts a wide net be­cause it acts through en­do­cannabi­noid re­cep­tors; CB1 and CB2, as well as oth­er re­cep­tors, such as GPR18, GPR55, GPR 119, 5HT1A, and TR­PV2. This sug­gests ther­a­peu­tic val­ue in a pletho­ra of con­di­tions due to its neu­ro­pro­tec­tive and im­munomod­u­la­to­ry prop­er­ties.

Pre­clin­i­cal stud­ies sug­gest CBD may have an­tipsy­chot­ic prop­er­ties, al­though cannabis use, in gen­er­al, is as­so­ci­at­ed with an in­creased risk of de­vel­op­ing psy­chosis. Bhat­tacharyya, of King’s Col­lege Lon­don, has been un­pack­ing the ev­i­dence sup­port­ing CBD’s ben­e­fit in psy­chosis pa­tients.

In a study pub­lished last year, Bhat­tacharyya et al in­ves­ti­gat­ed the neu­rocog­ni­tive mech­a­nisms that un­der­lie the pur­port­ed ther­a­peu­tic ef­fects of CBD in psy­chosis in a small place­bo-con­trolled tri­al (n=16 par­tic­i­pants with a clin­i­cal high risk (CHR) of psy­chosis re­ceived a sin­gle oral dose of 600 mg of CBD; n=17 such par­tic­i­pants re­ceived a place­bo, and n=19 con­trol par­tic­i­pants were not giv­en any drug). Each par­tic­i­pant was then stud­ied us­ing func­tion­al mag­net­ic res­o­nance imag­ing while per­form­ing a ver­bal learn­ing task. The re­searchers found that CBD could par­tial­ly nor­mal­ize al­ter­ations in parahip­pocam­pal, stri­atal, and mid­brain func­tion as­so­ci­at­ed with the CHR state.

Now, with a $1.2 mil­lion grant from Parkin­son’s UK, Bhat­tacharyya will lead the Parkin­son’s study, sched­uled to start in ear­ly 2020. There are cur­rent­ly 145,000 peo­ple liv­ing with Parkin­son’s in the Unit­ed King­dom, and da­ta sug­gest more than half will suf­fer from psy­chosis at some point.

The tri­al will be­gin with a six-week pi­lot to as­sess the safe­ty, tol­er­a­bil­i­ty, and ef­fec­tive­ness of phar­ma­ceu­ti­cal-grade CBD in pa­tients with Parkin­son’s-re­lat­ed psy­chosis.

CBD will be de­liv­ered oral­ly in cap­sules at a dose of up to 1,000 mg/day — in a bid to find an op­ti­mum dose. In the sec­ond tranche of the study, 120 pa­tients will be re­cruit­ed to a 12-week dou­ble-blind, place­bo-con­trolled study.

Re­cent­ly, there was one an­tipsy­chot­ic ap­proved for Parkin­son’s dis­ease psy­chosis, which is de­signed to work by in­ter­act­ing with 5HT2A re­cep­tors and to a less­er ex­tent 5HT2C re­cep­tors — in­stead of tar­get­ing the over­pro­duc­tion of dopamine.

Aca­dia’s $ACAD Nu­plazid was ap­proved in 2016, al­though an in­de­pen­dent pan­el to the FDA sug­gest­ed its ef­fi­ca­cy was not as ro­bust as it would have liked. It was al­so ap­proved with a black box warn­ing — which most an­tipsy­chotics car­ry — high­light­ing the high­er risk of death as­so­ci­at­ed with its use in the el­der­ly.

Nu­plazid, which gen­er­at­ed sales of about $146 mil­lion in the first half of this year, gained no­to­ri­ety af­ter a se­ries of re­ports sug­gest­ed its mak­er had mis­rep­re­sent­ed the dan­gers of us­ing the drug and em­ployed ques­tion­able tac­tics to mar­ket it, prompt­ing an FDA re­view, which even­tu­al­ly reaf­firmed the drug’s safe­ty pro­file.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

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.

Endpoints News

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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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UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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UP­DAT­ED: 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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Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.

Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.