Genen­tech dou­bles down on its PhI­II Alzheimer’s cam­paign for crenezum­ab

An­drea Pfeifer

Roche’s big biotech group Genen­tech is dou­bling down on one of the most promi­nent drugs in late-stage de­vel­op­ment for Alzheimer’s. The com­pa­ny is launch­ing a sec­ond Phase III study of crenezum­ab, ac­cord­ing to its part­ners at AC Im­mune $ACIU, in search of pos­i­tive da­ta in a field lit­tered with the wreck­age of ear­li­er clin­i­cal crash­es.

In­ves­ti­ga­tors for the CREAD2 study will now set out to re­cruit 750 pa­tients with pro­dro­mal or mild Alzheimer’s to test the drug, an­oth­er an­ti-amy­loid be­ta drug de­signed to sweep out tox­ic for­ma­tions that are be­lieved by many to cause the mem­o­ry-wast­ing ill­ness.

CREAD2 will start with all the hall­marks ex­pect­ed in an Alzheimer’s study. It failed a mid-stage pro­gram, but in­ves­ti­ga­tors were able to track a dis­tinct im­pact on cog­ni­tive and func­tion­al scores for pa­tients di­ag­nosed with the ear­li­est stages of this dis­ease. Re­turn­ing to Phase III proved to be a dis­as­trous mis­take for Eli Lil­ly’s solanezum­ab, a three time los­er. But AC Im­mune has been able to win over be­liev­ers that this time a piv­otal ef­fort can suc­ceed.

Jef­feries’ Pe­ter Welford not­ed that the launch of the sec­ond Phase III can now con­form to cur­rent FDA rules de­mand­ing two Phase III stud­ies for an ap­proval. And he out­lined the pro-crenezum­ab ar­gu­ment in a note this morn­ing, com­par­ing Roche’s drug with Lil­ly’s solanezum­ab.

(1) So­la tar­gets Abe­ta monomers on­ly, where­as crenezum­ab al­so tar­gets sol­u­ble Abe­ta oligomers, be­lieved by many to be the most neu­ro­tox­ic, in­hibits Abe­ta ag­gre­ga­tion and pro­motes dis­ag­gre­ga­tion of Abe­ta plaques; (2) The so­la study en­rolled mild AD pa­tients (base­line MMSE 20-26) some of whom may al­ready be too ad­vanced, with “treat­ment” pos­si­bly need­ed years be­fore clin­i­cal man­i­fes­ta­tions ap­pear as pre­ven­tion. The crenezum­ab Phase III stud­ies are en­rolling milder AD pa­tients, with base­line MMSE 22+ and CDR-GS 0.5 or 1.0. We note that Lil­ly has now al­so aban­doned an on­go­ing tri­al in pro­dro­mal AD; (3) Un­like oth­er promi­nent Abe­ta an­ti­bod­ies such as ad­u­canum­ab and so­la that have an IgG1 back­bone, crenezum­ab con­tains an IgG4 back­bone. Im­por­tant­ly, this IgG4 back­bone re­sults in clear­ance of Abe­ta with­out in­duc­ing an in­flam­ma­to­ry re­sponse, en­abling use of high­er dos­es and a bet­ter side ef­fect pro­file. High­er dos­es should re­sult in in­creased brain ex­po­sure and there­fore po­ten­tial­ly greater ef­fi­ca­cy.

Com­pa­nies in the field can re­ly on bet­ter di­ag­nos­tics to ac­tu­al­ly re­cruit the right pa­tients. But af­ter 15 years of de­feat and dis­as­ter in Alzheimer’s R&D, you can al­so ex­pect to see plen­ty of skep­ti­cism for a drug that al­ready failed hu­man stud­ies.

The litany of set­backs in­cludes Mer­ck’s re­cent de­ci­sion to scut­tle a Phase III study for the in­dus­try-lead­ing BACE drug. But any com­pa­ny which does man­age to get a drug across the fin­ish line can look for­ward to ma­jor sales. Mil­lions of Alzheimer’s pa­tients around the world are des­per­ate for some kind of dis­ease mod­i­fy­ing ther­a­py.

Jef­feries es­ti­mates peak sales for a crenezum­ab at $4.4 bil­lion in 2028, and oth­er an­a­lysts would stretch that fig­ure much high­er.

An­drea Pfeifer, the CEO of AC Im­mune, had this to say:

Giv­en the re­cent dis­ap­point­ing re­sults of oth­er ther­a­pies, all of us in the Alzheimer’s com­mu­ni­ty need to re­dou­ble our ef­forts to com­bat one of so­ci­ety’s biggest chal­lenges. We re­main con­fi­dent about the po­ten­tial of crenezum­ab giv­en it is dis­tinct from oth­er be­ta amy­loid an­ti­bod­ies, pre­dom­i­nant­ly block­ing oligomers in the brain, and has a clin­i­cal de­vel­op­ment pro­gram that is us­ing high­er dos­ing and tar­get­ing ear­li­er stages of Alzheimer’s dis­ease.

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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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.

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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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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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.

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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