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.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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Look­ing for 'ex­ter­nal in­no­va­tion,' Boehringer In­gel­heim re­serves $500M+ for new Shang­hai hub

Now that Boehringer Ingelheim’s bet on contract manufacturing in China has paid off, the German drugmaker is anteing up more to get into the research game.

Boehringer has set aside $507.9 million (€451 million) for a new External Innovation Hub to be built in Shanghai over five years. The site will become one of its “strategic pillars” as the team strives to get 71 approvals — either for new products or indications — by 2030, said Felix Gutsche, president and CEO of Boehringer Ingelheim China.

Vas Narasimhan, Novartis CEO (Patrick Straub/​EPA-EFE/​Shutterstock)

No­var­tis pays $678M for kick­back scheme as Vas Narasimhan tries to dis­tance phar­ma gi­ant from shady be­hav­ior

Novartis has reached another large settlement to resolve misconduct allegations, agreeing to pay more than $678 million to settle claims that it had spent hundreds of millions of dollars on lavish dinners, so-called speaking fees and expensive alcohol “that were nothing more than bribes” to get doctors to prescribe Novartis medications.

The top-shelf alcohol and lavish meals included a $3,250 per person night at Nobu in Dallas, a $672-per person dinner at Washington DC’s Smith & Wollensky and a $314 per person meal at Sushi Roku in Pasadena, according to the Justice Department complaint. There were at least 7 trips to Hooters and fishing trips in Alaska and off the Florida coast. Each of these events were supposed to be “speaker programs” where doctors educated other doctors on a drug, but the DOJ alleged many were “bogus” wine-and-dine events where the drug was barely mentioned, if at all.  (“Nobody presented slides on the fishing trips,” the complaint says.)

No­vavax snags Ben Machielse for CMC and pro­motes a trio of staffers; Mar­ty Du­vall lands an­oth­er CEO post at On­copep­tides

Novavax has been making waves recently by securing a $384 million commitment from CEPI to cover R&D and manufacturing for its Covid-19 vaccine while also spending $167 million on a 150,000 square-foot facility. The Maryland biotech continues to shore up its leadership team as well, bringing in Ben Machielse as their EVP of CMC just a couple weeks after nabbing AstraZeneca vet Filip Dubrovsky as their new CMO. Machielse was president and CEO of Vtesse from 2014-17, and before that, he also spent more than 11 years at MedImmune and was EVP of operations for the back half of his tenure.

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Dan Gold, MEI Pharma CEO

De­vel­op­ment part­ners at MEI, Helsinn dump a high-risk PhI­II AML study af­ter con­clud­ing it would fail sur­vival goal

Four years after Switzerland’s Helsinn put $25 million of cash on the table for an upfront and near-term milestone to take MEI Pharma’s drug pracinostat into a long-running Phase III trial for acute myeloid leukemia, the partners are walking away from a clinical pileup.

The drug — an HDAC inhibitor — failed to pass muster during a futility analysis, as researchers concluded that pracinostat combined with azacitidine wasn’t going to outperform the control group in the pivotal.

No­var­tis los­es biosim­i­lar ap­peal as court up­holds a 31-year mo­nop­oly by Am­gen's En­brel

A new court ruling has strengthened Amgen’s grip on the IP estate around Enbrel, keeping biosimilars of the autoimmune and inflammatory drug at bay until 2029.

Novartis, the patent challenger, isn’t throwing in the towel yet. In a statement noting the failed appeal, its generics division Sandoz noted its reviewing options, “including potential appeal to US Supreme Court.”

It’s been almost four years since the FDA approved Erelzi, Sandoz’s copycat version of Enbrel. While sales of the Pfizer-partnered drug in the US — the market Amgen is in charge of — have dipped slightly during that time, it remains a solid megablockbuster with 2019 revenue slightly above $5 billion.