Eli Lil­ly shut­ters the last PhI­II so­la study, cer­tain of fail­ure

David Ricks, Lil­ly

Eli Lil­ly has tak­en an­oth­er big re­verse step in its re­treat from solanezum­ab, the Alzheimer’s drug once con­sid­ered the com­pa­ny’s lot­tery tick­et in R&D.

Fol­low­ing the fail­ure of Ex­pe­di­tion 3, Lil­ly’s mas­sive­ly ex­pen­sive third at­tempt to come up with sol­id da­ta of its ef­fi­ca­cy, in­ves­ti­ga­tors have now washed their hands of Ex­pe­di­tion Pro, an­oth­er Phase III study mount­ed for pa­tients with prodomal dis­ease, when their mem­o­ry be­gins to fade but they can still func­tion well on a dai­ly ba­sis.

In a call with an­a­lysts on Tues­day, CEO David Ricks says that in light of the over­lap in Ex­pe­di­tion 3 and the Ex­pe­di­tion Pro study, there was no sci­en­tif­ic ba­sis to be­lieve they would find a “mean­ing­ful ben­e­fit to pa­tients with prodomal Alzheimer’s dis­ease.”

Lil­ly had set out to re­cruit 2,450 patents for Ex­pe­di­tion Pro, which was due to wrap in 2021.

In an­oth­er note, Lil­ly’s Q4 up­date in­clud­ed the end of a Phase I study for “A ß An­ti­body Fab PEG,” a new bi­o­log­ic en­ti­ty that had been stud­ied for Alzheimer’s dis­ease.

Ricks took over as CEO at the start of his year, and gets to start his tenure by large­ly bury­ing what re­mains of one of the biggest late-stage ef­forts in the in­dus­try, long pur­sued by John Lech­leit­er. An­a­lysts have long been re­luc­tant to give Lil­ly good odds on the drug, but in the off chance they were suc­cess­ful, many be­lieved it could have racked up $10 bil­lion in an­nu­al sales.

In­stead, the drug has be­come the lat­est vic­tim in a near com­plete clin­i­cal rout on the Alzheimer’s front, where re­searchers have been shut out of any im­por­tant ad­vances for the past decade.

Lil­ly is not quite fin­ished with so­la, though. The pre­clin­i­cal study in Alzheimer’s dis­ease (An­ti-Amy­loid Treat­ment in Asymp­to­matic Alzheimer’s “A4”), and Dom­i­nant­ly In­her­it­ed Alzheimer’s Dis­ease, known as ”DI­AN,” con­tin­ue).

Lil­ly’s most ad­vanced Alzheimer’s ef­fort now cen­ters on a BACE drug it in-li­censed from As­traZeneca (AZD3293), to re­place its own pro­gram that was scut­tled by tox­i­c­i­ty.

Dur­ing Tues­day’s Q&A with an­a­lysts, Lil­ly chief sci­en­tist Jan Lund­berg was giv­en the task of ex­plain­ing the com­pa­ny’s at­ti­tudes about the A be­ta hy­poth­e­sis, which it’s been ex­plor­ing for years. So­la was de­signed to get rid of tox­ic con­cen­tra­tions of amy­loid be­ta, which many be­lieve is a cause of the dis­ease. It’s worth quot­ing him at length.

The amy­loid-be­ta hy­poth­e­sis and the con­nec­tion to Alzheimer’s dis­ease has strong ev­i­dence from ge­net­ics, where if you have too much amy­loid in your brain, you get ear­ly Alzheimer’s dis­ease. And al­so the op­po­site, if you have less amy­loid-be­ta pro­duc­tion then by mu­ta­tions in the APP in the BACE1 cleav­age side, you al­so seem to be pro­tect­ed from de­men­tia.

The key ques­tion is so how do you trans­late then these ge­net­ics in­to re­al­i­ties of phar­ma­co­log­i­cal treat­ment in an aged pa­tient? And here there are a va­ri­ety of ap­proach­es that have been used. And it’s al­so a key one here to think about if you have an an­ti­body with ac­cess to brain, 0.1% through the blood/brain bar­ri­er, how can you com­pare that re­sult then to, for in­stance, an oral BACE in­hibitor, which some of them go 100% in­to the brain and are I think more like­ly to have a marked ef­fect than on the free amy­loid be­ta?

And the sec­ond ques­tion is clear­ly then how ear­ly do you have to treat? And I think we should rec­og­nize that even if you have mild Alzheimer’s dis­ease, your brain has been ac­cu­mu­lat­ing amy­loids for decades, and you al­most have max­i­mum amy­loid in your brain al­ready. So I think there could be two com­po­nents here, like I say. If solanezum­ab re­al­ly en­tered the brain enough to af­fect amy­loid be­ta, I think our bio­mark­ers like amy­loid PET didn’t re­al­ly change very much by solanezum­ab, nor did the ac­tu­al­ly tau then changes, which are more re­lat­ed to neu­rode­gen­er­a­tion change. So from that stand­point, we didn’t see any ob­jec­tive mea­sures I think that we changed the amy­loid con­tent in the brain, nor then neu­rode­gen­er­a­tion.

Is this against or does this prove that the amy­loid hy­poth­e­sis is wrong? My view is it’s too ear­ly to say. We need to wait for even more pow­er­ful agents. And the next in turn are the oral-based in­hibitors, which are more like­ly I think to have an even stronger ef­fect on the amy­loid be­ta in the brain. And in ad­di­tion then, we need to look at ear­li­er stages of Alzheimer’s.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.