Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An ear­ly-stage up­date on Ad­verum Biotech­nolo­gies’ in­trav­it­re­al gene ther­a­py has trig­gered in­vestor con­cern, af­ter pa­tients with wet age-re­lat­ed mac­u­lar de­gen­er­a­tion (AMD) saw their vi­sion de­te­ri­o­rate, de­spite signs that the treat­ment is im­prov­ing reti­nal anato­my.

Ad­verum, on Wednes­day, un­veiled 24-week da­ta from the OP­TIC tri­al of its ex­per­i­men­tal ther­a­py, AD­VM-022, in six pa­tients who have been ad­min­is­tered with one dose of the ther­a­py. On av­er­age, pa­tients in the tri­al had se­vere dis­ease with an av­er­age of 6.2 an­ti-VEGF in­jec­tions in the eight months pri­or to screen­ing and an av­er­age an­nu­al­ized in­jec­tion fre­quen­cy of 9.3 in­jec­tions.

Over the six month pe­ri­od, pa­tients did not re­quire any an­ti-VEGF res­cue in­jec­tions — and five of six pa­tients saw a com­plete re­sponse with a to­tal res­o­lu­tion of flu­id fol­low­ing the Ad­verum in­jec­tion. There were no se­ri­ous ad­verse events, and the ma­jor­i­ty of side-ef­fects were mild.

How­ev­er, pa­tients lost vi­su­al acu­ity by two let­ters on av­er­age, with a 90% con­fi­dence in­ter­val of -9.1 let­ters to +5.1 let­ters.

Mani Foroohar

“The range of in­di­vid­ual pa­tient da­ta were not pre­sent­ed, though the wide con­fi­dence in­ter­val sug­gests that some pa­tients may have ex­pe­ri­enced a loss of more than 10 let­ters dur­ing the course of the tri­al – lack of res­cue in­jec­tions is dif­fi­cult to square with de­clin­ing vi­sion.” SVB Leerink’s Mani Foroohar wrote in a note.

“How­ev­er, the study in­ves­ti­ga­tor in­sist­ed no loss in vi­sion was due to wet AMD pathol­o­gy and ob­served loss of vi­su­al acu­ity is due to nor­mal vari­abil­i­ty…in a small set of pa­tients – an as­ser­tion that, if proved out with ad­di­tion­al fol­low-up, would very sub­stan­tial­ly im­prove the im­plied qual­i­ty of this dataset.”

Shares of the com­pa­ny — which spec­tac­u­lar­ly failed years ago when it was chris­tened Avalanche Biotech­nolo­gies — $AD­VM were down about 6.8% to $5.56 in Fri­day pre­mar­ket trad­ing. The stock sank on Thurs­day, evap­o­rat­ing mil­lions from its mar­ket val­ue.

“This da­ta sug­gest AD­VM-022 is po­ten­tial­ly ac­tive in de­liv­er­ing an ex­press­ible gene cas­sette in wet AMD, but mixed sig­nals in this small dataset should lift some of the com­pet­i­tive over­hang on RGNX shares,” Foroohar added. Re­genexBio ex­per­i­men­tal gene ther­a­py for wet AMD, RGX-314, is cur­rent­ly in a Phase I/II tri­al.

Wet AMD, which is char­ac­ter­ized by blurred vi­sion or a blind spot in an in­di­vid­ual’s vi­su­al field, is typ­i­cal­ly caused by ab­nor­mal growth of blood ves­sels that leak flu­id or blood in­to the mac­u­la. Mac­u­lar de­gen­er­a­tion is the lead­ing cause of se­vere, ir­re­versible vi­sion loss in the el­der­ly. An­ti-VEGF in­jec­tions such as Re­gen­eron’s $REGN flag­ship Eylea, as well as Roche’s $RHB­BY Lu­cen­tis and Avastin, are com­mon­ly used to treat wet AMD.

In April, the FDA im­posed a clin­i­cal hold on an ap­pli­ca­tion to test AD­VM-022 in hu­mans, ask­ing for ad­di­tion­al da­ta on Ad­verum’s chem­istry, man­u­fac­tur­ing and con­trol process. In May, the hold was lift­ed. Late last year, the biotech aban­doned its then lead ex­per­i­men­tal drug, AD­VM-043, for the treat­ment of A1AT de­fi­cien­cy.

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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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.

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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?

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.