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.

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,400+ biopharma pros reading Endpoints daily — and it's free.

ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.