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.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

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Democratic presidential candidate, U.S. Sen. Elizabeth Warren (D-MA) speaks during the Nevada Democrats' "First in the West" event at Bellagio Resort & Casino on November 17, 2019 in Las Vegas, Nevada (Getty Images)

Eliz­a­beth War­ren pro­pos­es us­ing com­pul­so­ry li­cens­ing, an­titrust ac­tions to break bio­phar­ma’s con­trol of drug pric­ing — and here are the block­busters she’s tar­get­ing first

Nancy Pelosi’s drug pricing bill may have sparked some industrial strength headaches on the money side of biopharma, but Elizabeth Warren seems determined to become biopharma’s Nightmare on Pennsylvania Avenue.
Warren, one of the top-ranked candidates for the Democratic presidential nomination backing Medicare for all, is circulating a new plan that promises to break the industry’s grip on drug prices — and she has some very specific examples of how she would do it.
The Warren plan would rely on the federal government’s compulsory licensing powers to seize the IP of blockbuster drugs like Truvada and Harvoni to provide them at a fraction of what Gilead sells them for in the US. And she would throw some antitrust actions in as needed to rein in the price of Humira, AbbVie’s cash cow that continues to dominate the list of the most profitable therapeutics on the market.
Notably, she plans to rely on the powers already vested in the federal government, rather than suggest remedies that would require the assent of a deeply divided Congress.
In addition to the blockbusters on the list, Warren sends a clear signal that the same tactics would be used to beef up the supply of cheap antibiotics, as needed. And the same action could befall any other therapy patients can’t afford.

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Mer­ck’s $1B cash gam­ble pays off with a sur­pris­ing PhI­II car­dio suc­cess for Bay­er’s heart drug veri­ciguat

More than 3 years after Merck stepped up and paid $1 billion in cold, hard cash to gain the US commercial rights to Bayer’s high-risk heart drug vericiguat in a broad-ranging cardio alliance, the partners say their Phase III study has come through with promising data and a date with regulators.
We don’t have the data, and won’t until they put it out at an upcoming scientific session, but Merck touted the results, saying that their big Phase III VICTORIA study hit the primary endpoint  — with vericiguat combined with available therapies reducing “the risk of the composite endpoint of heart failure hospitalization or cardiovascular death in patients with worsening chronic heart failure with reduced ejection fraction (HFrEF) compared to placebo when given in combination with available heart failure therapies.”
Depending on the hard data, and how it breaks out with the combinations used, this drug could pose a threat to Novartis’ blockbuster drug Entresto, currently at $1.6 billion while analysts expect peak sales to hit $4 billion.
The drug is a soluble guanylate cyclase (sGC) stimulator, which Bayer and Merck have had high hopes for. Evidently, so did cardiologists. Cowen’s last analysis set potential sales at $400 million in 2024, but that number could go up significantly now.
Cowen’s Steve Scala noted this morning:
Vericiguat could be a lucrative product for Merck, and one with potentially under-appreciated value. At Cowen’s Therapeutics Conference in September 2019, 80% of specialists anticipated a positive result from VICTORIA whereas only 51% of investors shared this optimism.
Investigators recruited more than 5,000 patients at more than 600 centers in 42 countries for this study — one of the most expensive propositions in R&D. Millions of people in the US suffer from heart failure with reduced ejection fraction when the failing heart fails to contract properly to eject blood into the system. Bayer holds ex-US rights to the drug and also stands to earn cash from the $1.1 billion in milestones Merck agreed on for their collaboration.
Remarkably, the drug was pushed into Phase III despite failing the mid-stage trial — though investigators flagged a success at the high dose of 10 mg. In VICTORIA, researchers started patients at 2.5 mg and then titrated up to 5 and then 10 mg.

Alk­er­mes forges $950M biotech buy­out deal in a bold bet on an ear­ly-stage CNS drug plat­form

Alkermes $ALKS is investing $100 million cash and committing up to $850 million more in milestones in a big wager on a very early-stage CNS discovery platform. And the biotech is adding $20 million more to fund next year’s new research work on the platform it’s acquiring in today’s buyout with an eye to expanding the research work in oncology.

The biotech, helmed by Richard Pops, is buying Rodin Therapeutics, which had focused early on Alzheimer’s disease. Pops’ buyout, though, isn’t focused solely on the most troublesome sector in pharma R&D.

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(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.

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Left to right: Arthur Pappas, Robert Nelsen, Peter Kolchinsky Doug Cole and David Beier

In rare po­lit­i­cal for­ay, top biotech in­vestors urge Con­gress to re­ject drug pric­ing bill

Thirteen of the top biotech venture capitalists in the country wrote a letter last week warning lawmakers that if Congress passes a drug pricing bill House Speaker Nancy Pelosi has put before lawmakers, they won’t be able to invest in biomedical research at their current rate, and patients will suffer.

“If policies such as those included within H.R. 3, the Lower Drug Costs Now Act, are passed, our ability to continue to invest in future biomedical innovation will be severely constrained, thus crushing the hopes of millions of patient waiting for the next breakthroughs to treat or cure their cancers, rare genetic diseases, Alzheimer’s, or other serious and life-threatening conditions,” they wrote in a letter addressed to the highest-ranking Democrats and Republicans in the House and Senate and acquired by Endpoints News. 

Dicer­na scores broad, 'rest of liv­er' deal with No­vo Nordisk, bag­ging $225M in cash to hit some 30 tar­gets with RNAi plat­form

Turns out Dicerna wasn’t done with deals yet after locking in $200 million upfront from Roche for a hepatitis B cocktail two weeks ago.

Novo Nordisk has signed on as the latest partner to its GalXC RNAi platform, handing over $175 million in cash to claim any and all targets of interest in liver-related cardio-metabolic diseases that are not already reserved in previous pacts. The Danish drugmaker — which has signaled its interest to expand considerably beyond its core diabetes franchise into areas like NASH — is also purchasing $50 million worth of Dicerna’s equity at a 25% premium of $21.93 per share. More research payments and milestones extending to the billions are on the line.

Gene ther­a­py wins the in­side track at EMA; PPD files for IPO

→ Gene therapy maker Orchard Therapeutics has been granted an accelerated assessment for OTL-200 by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The gene therapy — in development in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy — being used towards the treatment of metachromatic leukodystrophy.

→ Pharmaceutical Product Development has announced that its parent company, PPD, Inc has submitted a draft to the SEC relating to the proposal of an IPO of the parent company’s common stock. Number of shares and price range have not yet been determined.