Vi­iV's Dova­to wins speedy US ap­proval with PRV, em­pow­er­ing GSK to mus­cle in­to Gilead­'s HIV em­pire

GSK’s Vi­iV is poised to take a bite out of Gilead’s HIV em­pire, af­ter its dual HIV reg­i­men — Dova­to — se­cured FDA ap­proval on Mon­day, af­ter the British drug­mak­er sub­mit­ted its mar­ket­ing ap­pli­ca­tion with a pri­or­i­ty re­view vouch­er (PRV) last Oc­to­ber, en­abling a speedy re­sponse from the US reg­u­la­tor.

Deb­o­rah Wa­ter­house

Dova­to is an im­prove­ment over GSK’s ex­ist­ing two-drug reg­i­men Ju­lu­ca, which does not in­clude a nu­cle­o­side ana­log re­verse tran­scrip­tase in­hibitor or a ‘nuke.’ This fam­i­ly of drugs are used to thwart an en­zyme called re­verse tran­scrip­tase, which is used by the HIV virus to make copies of it­self in­side a healthy cell.

Akin to Ju­lu­ca, GSK’s new two-drug reg­i­men Dova­to al­so in­cludes its in­te­grase in­hibitor, do­lute­gre­vir (DTC). In­te­grase in­hibitors, such as do­lute­gre­vir and Gilead’s bicte­gre­vir, work against HIV’s in­te­grase pro­tein, block­ing its abil­i­ty to in­te­grate its ge­net­ic code in­to hu­man cells.

How­ev­er, un­like Gilead, GSK has a chron­ic is­sue with its HIV com­bi­na­tion reg­i­mens: sub­op­ti­mal nukes, Ever­core ISI’s Umer Raf­fat high­light­ed in a note. For ex­am­ple, GSK’s Tri­umeq — which in­cludes DTC and two nukes — fea­tures aba­cavir, a nuke that has been linked to hy­per­sen­si­tiv­i­ty and CV is­sues, he said, un­der­scor­ing that due to patent is­sues GSK was not able to use a nuke bet­ter than aba­cavir in the past.

This has had an im­pact on GSK’s HIV sales. Pre­scrip­tion vol­umes in­di­cate that de­mand for its DTC monother­a­py, Tivicay, and DTC com­bo Tri­umeq are sim­i­lar, ac­cord­ing to Raf­fat. In ef­fect, it looks like half the pa­tients tak­ing DTC un­der­go the has­sle of tak­ing an­oth­er pill in ad­di­tion to Tivicay: Gilead’s clean two-nuke com­bo Tru­va­da, he said.

Due to these is­sues, Gilead’s sin­gle tablet with two good nukes in it — Bik­tarvy — has done ex­treme­ly well, Raf­fat not­ed.

Umer Raf­fat

With the Dova­to ap­proval, GSK now has a prod­uct that does not re­quire sep­a­rate Tru­va­da ad­min­is­tra­tion, does not in­clude an aba­cavir com­po­nent which has safe­ty con­cerns, and can com­pete di­rect­ly against Bik­tarvy. (Al­though the da­ta from pa­tients in Botswana sug­gest­ed a link be­tween DTC and birth de­fects, prompt­ing the WHO to rec­om­mend that women in the ear­ly stages of their preg­nan­cy not use the drug). In ad­di­tion, GSK’s Dova­to fea­tures an off-patent nuke called lamivu­dine, which al­lows for a com­par­a­tive­ly cheap­er list price ver­sus Bik­tarvy.

Ac­cord­ing to Raf­fat, Bik­tarvy car­ries an­nu­al price tag of $37,000, while Dova­to is 26% cheap­er at $27,500.

GSK’s ap­proach to grab­bing mar­ket share from Gilead $GILD  — which cur­rent­ly dom­i­nates the HIV mar­ket that is es­ti­mat­ed to hit $22.5 bil­lion by 2025 — is to con­vince reg­u­la­tors, doc­tors and pa­tients to adopt its two-drug reg­i­mens, ver­sus Gilead’s triple-drug cock­tails, that could po­ten­tial­ly re­sult in few­er tox­ic side-ef­fects, re­duce dos­ing fre­quen­cy, and be more cost-ef­fec­tive — al­though crit­ics sug­gest this may not be the most ef­fec­tive strat­e­gy be­cause the virus will on­ly have to fight against two drugs which could cul­mi­nate in drug re­sis­tance.

Re­sults of two phase III GEM­I­NI tri­als test­ing Dova­ta pre­sent­ed last year showed that GSK’s ther­a­py worked as well as stan­dard three-drug ther­a­py in treat­ment-naive pa­tients with both low and high lev­els of the virus, and sig­nif­i­cant­ly, no pa­tient in the 1,400 pa­tients en­rolled across the tri­als, de­vel­oped drug re­sis­tance. This was a cru­cial wor­ry as there was a re­port­ed case of drug re­sis­tance in a pre­vi­ous study.

The reg­i­men is cur­rent­ly un­der re­view in Eu­rope, Cana­da, Aus­tralia, Switzer­land, and South Africa.

Ac­cord­ing to WHO es­ti­mates, 36.9 mil­lion peo­ple were liv­ing with HIV glob­al­ly in 2017. The best way to thwart the spread of HIV is to use con­doms. But for those al­ready af­flict­ed with the virus, an­ti­retro­vi­ral ther­a­py must be tak­en every sin­gle day to sup­press the virus or un­bri­dled repli­ca­tion can over­whelm the im­mune sys­tem and even­tu­al­ly cause AIDS. Dai­ly pills al­so rack up ex­pen­sive bills in the Unit­ed States, with month­ly ex­pen­di­ture on treat­ment hit­ting thou­sands per month — de­pend­ing on the reg­i­men, in­sur­ance provider and re­bates/dis­counts.

“With Dova­to, the first com­plete, sin­gle-tablet, two-drug reg­i­men for treat­ment-naïve adults, Vi­iV Health­care is de­liv­er­ing what pa­tients are re­quest­ing—a chance to treat their HIV-1 in­fec­tion with as few drugs as pos­si­ble,” Vi­iV chief Deb­o­rah Wa­ter­house said in a state­ment.

Vi­iV was es­tab­lished in 2009 by GSK $GSK in part­ner­ship with Pfiz­er $PFE, with Sh­iono­gi join­ing as a share­hold­er in 2012.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,900+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis is eye­ing a multi­bil­lion-dol­lar Med­Co buy­out as Jer­sey biotech nears NDA — re­ports

To get from Novartis’ US headquarters to the Medicines Company, you make a left out of a square concrete building on NJ-Route 10, follow it past the sun orange veranda of Jersey’s Hot Bagels and the inexplicable green Vermont cabin that houses the Whippany Railway Museum until you turn right and immediately arrive at a rectangular glass building. It should take you about 12 minutes.

Reports are out that Novartis may be making that trip. Amid a torrent of Phase III data burnishing MedCo’s chances at a blockbuster cholesterol drug,  Bloomberg News is reporting that Novartis is looking to acquire the Jersey-based biotech.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,900+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,900+ biopharma pros reading Endpoints daily — and it's free.

Badrul Chowdhury. FDA via Flickr

As­traZeneca los­es an­oth­er ex­ec­u­tive to biotech, as Badrul Chowd­hury moves to Savara

Another executive is migrating from the echelons of Big Pharma to the corridors of small biotech.

In April 2018, Badrul Chowdhury took his more than two decades of experience at the FDA to AstraZeneca, where he took on the role of senior vice president and chief physician-scientist for respiratory, inflammation and autoimmunity late-stage development in biopharmaceuticals R&D.

After about a year and a half in this role, Chowdhury is moving to a small Texas biotech called Savara, where he will serve as chief medical officer.

Yiannis Kiachopoulos and Artur Saudabayev, co-founders of Causaly

Lon­don AI up­start, which counts No­var­tis as a cus­tomer, can teach your com­put­er to read

When Amazon developed a machine-learning tool to make its recruitment process more efficient — the man-made system absorbed the gender-bias of its human makers, and the project was aborted. In the field of biopharmaceuticals, the way researchers train their machine learning algorithms can skew the outcome of predictions. But before those predictions can be made, the engine must learn to read to make sense of explosive volume of knowledge out there.

Burt Adelman. Novo Ventures

Here's a $25M seed fund aimed at back­ing some brash new drug ideas out of the Broad

As a former academic and a seasoned drug developer, Burt Adelman knew when he was recruited as a senior advisor to Novo Ventures in 2017 that one of his key priorities needs to be introducing the fund to the network he was so deeply embedded in.

“I was thinking long and hard on how can I, as a Boston insider, help Novo really get inside the ecosystem of Boston biotech?” he recalled in an interview with Endpoints News.

Welling­ton lines up a $393M bankroll for its next round of pri­vate biotech bets — and they’re like­ly think­ing big

Wellington Management made some uncustomary waves at the beginning of the year when it threw its considerable weight against Bristol-Myers Squibb’s $74 billion Celgene buyout. But after Bristol-Myers’ biggest investor conceded that game to the influential proxy firms involved, they’re now going to end the year by rolling out a big new investment fund for a new stable of fledgling biotechs on the private side of the industry.

As uter­ine race with Ab­b­Vie heats up, My­ovant eyes FDA ap­proval with tri­al re­sults from prostate can­cer

Myovant has long had a secret weapon in its uterine rivalry with AbbVie: Men.

While the small Swiss biotech has jockeyed with the Illinois-based giant for a foothold in the endometriosis and uterine fibroid therapy market, the company has been developing the same lead compound, relugolix, for use in one of the most common cancers for the uterus-less: prostate cancer. Today, Myovant is out with positive topline results from its big Phase III trial on the gonadotropin-releasing hormone (GnRH) antagonist. They say they’ve reached every primary and secondary endpoint with p values less than .0001.