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.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

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It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

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ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

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Mil­li­pore­Sig­ma to build new $20 mil­lion, 12,000-square-foot lab in Switzer­land

On the heels of opening a new laboratory in Shanghai last week, MilliporeSigma is continuing its construction push.

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Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

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When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

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Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

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