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.

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,600+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,600+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,600+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,600+ biopharma pros reading Endpoints daily — and it's free.

As­traZeneca gains EU nod for di­a­betes triple; Am­gen and Duke launch re­al-world PC­SK9 ob­ser­va­tion­al study

→ Weeks after winning EU approval to start marketing dapagliflozin as Forxiga, AstraZeneca has racked up another OK for a triplet combo involving the SGLT2 diabetes drug. Named Qtrilmet, the pill combines Forxiga with the DPP-4 inhibitor Onglyza (saxagliptin) and the bedrock drug metformin in a modified-release format. That 3-in-1 approach proved superior in reducing average blood glucose levels to a number of other dual combinations across 5 Phase III trials, including Forxiga plus metformin, Onglyza with metformin, or glimepiride with metformin.

Five drugs, in­clud­ing two No­var­tis ther­a­pies, win EMA en­dorse­ment

As is custom, an EMA panel on Friday issued its weekly recommendations on marketing applications submitted by drug developers. This week, the agency backed the use of five new therapies — including two Novartis drugs — but issued no negative reviews.

Novartis’ S1P drug for relapsing forms of multiple sclerosis (MS) drug, Mayzent (known chemically as siponimod), which was approved by the FDA in March — has been given the nod by the EMA. The Swiss drugmaker already sells its other MS drug, Gilenya, in both regions.

Atom­wise's X-37 spin­out gets $14.5 mil­lion to launch AI dis­cov­ery ef­forts

The folks behind Atomwise’s spinout X-37 like to think in cosmological metaphors, and you can think of their AI drug development model as probes sent into space from a central station. That station just got $14.5 million in Series A funding from DCVC Bio, Alpha Intelligence Capital and Hemi Ventures to back those missions.

X-37 uses Atomwise’s AI platform to identify drug targets and – unlike the parent company, which largely sticks to computers  – bring those into a wet lab and preclinical testing.  In addition to AI professionals, it’s led in by part by drug developers from Velocity Pharmaceutical Development.

Ab­bott Lab­o­ra­to­ries CEO Miles White pass­es ba­ton down to suc­ces­sor; Lon­za CEO Marc Funk hits the ex­it

→ Abbott Laboratories has named a successor to CEO Miles White after he announced that he was stepping down in March after 21 years of service. Robert Ford, the company’s COO and president, will take the helm. Ford is known for his work in the $25 billion merger between St. Jude Medical into Abbott in January 2017. White will remain with the company as executive chairman of the board. 

→ After snapping up Novartis’ Swiss facility, Novartis Center of Excellence, in July, Lonza has announced that their CEO, Marc Funk, is hitting the exit for “personal reasons.” Funk has been the CEO of the company for less than a year — brought onto the company back in March. In the meantime, chairman Albert Baehny will serve as interim CEO. 

UCB adds on more pos­i­tive PhI­II da­ta for IL-17A/17F in­hibitor bimek­izum­ab, clear­ing a path to the FDA

A month after posting positive top-line data from their first Phase III trial of the IL-17A/17F inhibitor bimekizumab, Belgium’s UCB says they’ve added more upbeat results from their second late-stage test in moderate-to-severe plaque psoriasis.

That leaves the company on track for regulatory submissions in the middle of next year, says CMO Iris Loew-Friedrich.
Their drug beat out a placebo on the co-primaries — a 90% improvement in PASI 90 (the Psoriasis Area and Severity Index) and Investigator Global Assessment (IGA) response of clear or almost clear (IGA 0/1) at week 16, compared to placebo. Investigators also boasted of hitting some key secondaries.
UCB is angling to enter an increasingly crowded market space.
In their first of 3 Phase III studies for bimekizumab, researchers touted top-line wins on statistically significant results on clearing plaque psoriasis, including a victory over J&J’s IL-23 contender Stelara on key endpoints. The drug targets both IL-17A and IL-17F, a modification on the IL-17A strategy laid out for Taltz (Eli Lilly) and Cosentyx (Novartis). And the new group also includes J&J’s Tremfya and AbbVie’s Skyrizi.

Social image: UCB