Scripps-led con­sor­tium scores $129M NIH grant to work on vac­cine for stub­born HIV

Sci­en­tif­ic ef­fort in­to de­vel­op­ing a vac­cine against the HIV has proved elu­sive, as the virus rapid­ly mu­tates and its out­er spike pro­tein op­er­ates as an in­vis­i­bil­i­ty cloak, al­low­ing it to out­wit the im­mune sys­tem’s de­fen­sive ar­se­nal. On Wednes­day, a con­sor­tium of sci­en­tists led by Scripps Re­search un­veiled a $129 mil­lion grant from the Na­tion­al In­sti­tutes of Health (NIH) that will help shep­herd vac­cines — en­gi­neered to com­bat a pletho­ra of HIV strains — in­to the clin­ic.

HIV was once a death sen­tence, but is now con­sid­ered a chron­ic ill­ness. For those al­ready af­flict­ed, 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. Then there’s pre­ven­ta­tive treat­ment or PrEP (pre-ex­po­sure pro­phy­lax­is), in which in­di­vid­u­als at high risk for HIV (typ­i­cal­ly men who have sex with men) take med­i­cines dai­ly to low­er their chances of con­tract­ing the in­fec­tion. Ac­cord­ing to the CDC, dai­ly PrEP re­duces the risk of get­ting HIV via sex­u­al in­ter­course by more than 90%.

Still, there are near­ly 37 mil­lion peo­ple liv­ing with HIV/AIDS glob­al­ly, ac­cord­ing to World Health Or­ga­ni­za­tion fig­ures from 2017, a year which al­so saw 940,000 pa­tients suc­cumb to the dis­ease. Ac­cord­ing to Scripps, de­spite ex­ist­ing pre­ven­tion mea­sures, glob­al­ly 1.8 mil­lion peo­ple ac­quired HIV in 2017 (about one per­son every 15 sec­onds).

Den­nis Bur­ton Scripps Re­search

A key chal­lenge re­searchers face is that one HIV-af­flict­ed per­son can car­ry hun­dreds of thou­sands of vari­ants of the virus at any giv­en point. Scripps’ sci­en­tist Den­nis Bur­ton and his col­leagues ini­ti­at­ed their quest in 2009 when they dis­cov­ered two po­tent an­ti­bod­ies in the blood cells of a woman liv­ing with HIV that ap­peared ca­pa­ble of neu­tral­iz­ing 70% of 162 HIV ref­er­ence strains rep­re­sen­ta­tive of the glob­al epi­dem­ic.

Tak­ing a cue from this find­ing, Bur­ton et al. iden­ti­fied sta­ble re­gions on HIV’s out­er coat that could be tar­get­ed by bn­Abs to de­vel­op im­muno­gens. These mol­e­cules in an­i­mal stud­ies demon­strat­ed the abil­i­ty to con­fer long-last­ing pro­tec­tion against ex­po­sure to mul­ti­ple HIV strains. This work was sup­port­ed by a $77 mil­lion NIH grant which ran out this June.

This new cap­i­tal in­jec­tion will be used to re­fine the im­muno­gens, de­vel­op scal­able man­u­fac­tur­ing ap­pa­ra­tus­es, and test the im­muno­gens in ear­ly-stage hu­man clin­i­cal tri­als. In part­ner­ship with the In­ter­na­tion­al AIDS Vac­cine Ini­tia­tive, the con­sor­tium of re­searchers are set to launch their first hu­man clin­i­cal tri­al this year, Scripps said.

The promise of an HIV vac­cine first be­came ap­par­ent in 2009, when a tri­al in Thai­land test­ed a com­bi­na­tion of two vac­cines. In the tri­al, one vac­cine was giv­en in four dos­es and then “boost­ed” by two dos­es con­tain­ing both vac­cines. The analy­sis showed the group re­ceiv­ing the vac­cine(s) had an in­fec­tion rate 31.2% low­er than the group that re­ceived the place­bo — while this da­ta was not com­pelling enough to make the cut for ap­proval, the lessons of this tri­al are now be­ing used for a va­ri­ety of oth­er ef­forts.

Last year, a study pub­lished in the Lancet jour­nal from a sim­i­lar­ly struc­tured study of­fered en­cour­ag­ing re­sults. Re­searchers from NIH, Har­vard, J&J $JNJ and else­where used the same process of dos­ing a vac­cine and then fol­lowed up the ini­tial ad­min­is­tra­tion with ‘boost­er’ dos­es in non-in­fect­ed pa­tients at low risk of HIV. Da­ta showed the vac­cine reg­i­mens were well tol­er­at­ed and in­duced ro­bust im­mune re­spons­es in healthy in­di­vid­u­als — they are now be­ing test­ed in sub-Sa­ha­ran Africa.

So­cial im­age: Shut­ter­stock

Mer­ck is tak­ing the ax to its US op­er­a­tions, cut­ting 500 jobs in its lat­est re­or­ga­ni­za­tion

Merck is cutting 500 jobs in its US sales and headquarters commercial teams in its latest effort to find new ways to streamline the operation.

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Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Flu Virus (Source: CDC)

FDA ex­pands Xofluza ap­proval as Roche strug­gles to catch loom­ing flu mar­ket

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

EMA backs sev­en ther­a­pies, in­clud­ing Mer­ck­'s Ebo­la vac­cine

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.

Ronald Herb­st fol­lows Med­Im­mune ex­o­dus to Pyx­is CSO post; Jeff God­dard to suc­ceed CEO of AIT Bio­science

→ The outflow of top execs from MedImmune continues to fill the leadership ranks of smaller biotechs. The latest to take off is Ronald Herbst, the head of oncology research, who’s assuming the CSO post at Pyxis Oncology.  

Herbst was part of the old MedImmune organization AstraZeneca CEO Pascal Soriot restructured earlier this year, reorganizing the company and eliminating the storied subsidiary as a separate organization.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

UP­DAT­ED: J&J's Xarel­to, Amar­in's Vas­cepa are cost-ef­fec­tive, not bud­get friend­ly — ICER

ICER, an increasingly influential cost-effectiveness watchdog in the United States, has concluded in its review of treatments for cardiovascular disease that while the cost of J&J’s Xarelto and Amarin’s Vascepa meet its benchmark for value pricing — the two treatments will not likely treat as many patients as hoped without surpassing the annual budget threshold calculated by ICER for each therapy.