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.

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

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Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

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In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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Covid-19 roundup: J&J, BAR­DA set ear­ly 2021 fin­ish line for $1B vac­cine race; FDA al­lows emer­gency drug use, ahead of piv­otal da­ta

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That kind of accelerated timeline would fall on the fast side of NIAID director Anthony Fauci’s well-publicized prediction that it would be another 12 to 18 months before a vaccine can be available for public use. A Phase I trial of Moderna’s mRNA vaccine began two weeks ago, and both the biotech and fellow mRNA player CureVac have discussed similar, if not even faster, timelines for emergency use among healthcare workers.

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It is 'kind of a proven tech­nol­o­gy': Hep B vac­cine mak­er joins glob­al hunt for coro­n­avirus vac­cine

Using lab-grown proteins that are engineered to mimic the architecture of viruses to induce an immune response, VBI Vaccines is joining the hunt for a coronavirus vaccine — harnessing technology that has initially been proved safe in early trials as a prophylactic for cytomegalovirus (CMV) infection.

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The biotech is Waltham, MA-based Affinia and the two execs are Sean Nolan and Rick Modi — the former CEO and CBO respectively of AveXis, the gene therapy pioneer that fetched $8.7 billion in a sale to Novartis. Nolan has now taken the chairman’s role at Affinia while Modi moves up to the CEO post at the company.

Un­de­terred by a pan­dem­ic, Gilde Health­care rais­es their largest fund yet

When Pieter van der Meer started raising the capital for Gilde Healthcare’s fifth fund in the waning months of 2019, he had his eyes on a different chain of events that could change the healthcare system and perhaps even play to his firm’s advantage: The US presidential election.

Since raising their third fund in 2011, the 34-year-old Dutch firm had focused on value-based care. They chose late-stage biotechs that came up with new devices and delivery systems for de-risked established compounds, and when they chose preclinical biotechs, they spoke with potential pharma partners, payers and regulators to ask where and at what prices the drug made sense. As the Democratic primary became a contest over how to lower healthcare costs, it looked like a strategy that could pay off.

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Gilead CEO Dan O'­Day of­fers a de­tailed ex­pla­na­tion on remde­sivir ac­cess — re­as­sur­ing an­a­lysts that Covid-19 da­ta are com­ing fast

After coming under heavy fire from consumer groups ready to pummel them for grabbing the FDA’s orphan status for remdesivir — reserved to encourage the development of rare disease therapies — Gilead CEO Daniel O’Day had some explaining to do about the company’s approach to providing access to this drug to patients suffering from Covid-19. And he set aside time over the weekend to patiently explain how they are making their potential pandemic drug available in a new program — one he feels can better be used to address a growing pack of infected patients desperately seeking remdesivir under compassionate use provisions.

In addition to trying to reassure patients that they will once again have an avenue to pursue access, O’Day also reassured some analysts who had been fretting that China’s quick comeback from the coronavirus outbreak could derail its ultra-fast schedule for testing the drug in patients. The data are still expected in a few weeks, he says in the letter, putting the readout in April.

O’Day emphasizes that Gilead intends to pursue a pricing approach that will make this drug widely available — if it proves effective and safe. But no one is quite sure just what the longterm value would be, given the work being done on a variety of vaccines that may be rolled out as early as this fall — at least to the most heavily threatened groups.

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