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.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

In his 13 years at Genzyme, Michael Wyzga noticed something about East Coast drugmakers. Execs would often jet from Boston or New York to San Francisco to find more assets, and completely miss the work being done in flyover states, like Texas or Wisconsin.

“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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Ad­comm splits slight­ly in fa­vor of FDA ap­prov­ing Chemo­Cen­tryx’s rare dis­ease drug

The FDA’s Arthritis Advisory Committee on Thursday voted 10 for and 8 against the approval of ChemoCentryx’s $CCXI investigational drug avacopan as a treatment for adults with a rare and serious disease known as anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis.

The vote on whether the FDA should approve the drug was preceded by a split vote of 9 to 9 on whether the efficacy data support approval, and 10 to 8 that the safety profile of avacopan is adequate enough to support approval.

Paul Hastings, Nkarta CEO

With no up­front pay­ment or mile­stones on the line, Nkar­ta and CRISPR join forces on CAR-NK search

Most deals in biotech come with hefty upfront payments attached, and the promise of big biobucks if a program works out. Not this one.

Nkarta has struck what CEO Paul Hastings calls a “real collaboration” with CRISPR Therapeutics to co-develop and commercialize two CAR-NK therapies, in addition to an NK+T program. The duo will split all R&D costs — and any worldwide profits — 50/50, Hastings said.

Brent Saunders (Richard Drew, AP Images)

OcuWho? Star deal­mak­er turned aes­thet­ics czar Brent Saun­ders flips back in­to biotech. But who’s he team­ing up with now?

Brent Saunders went on a tear of headline-blazing deals building Allergan, merging and rearranging a variety of big companies into one before an M&A pact with Pfizer blew up and sent him on a bout of biotech drug deals. That didn’t work so well, so under pressure, he got his buyout at AbbVie — which needed a big franchise like Botox. And it was no big surprise to see him riding the SPAC wave into a recent $1 billion-plus deal that left him in the executive chairman’s seat at an aesthetics outfit — now redubbed The Beauty Health Company — holding a big chunk of the equity.

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Drug pric­ing watch­dog joins the cho­rus of crit­ics on Bio­gen's ad­u­canum­ab: What about charg­ing $2,560 per year?

As if Biogen’s aducanumab isn’t controversial enough, the researchers at drug pricing watchdog ICER have drawn up the contours of a new debate: If the therapy does get approved for Alzheimer’s by June, what price should it command?

Their answer: At most $8,290 per year — and perhaps as little as $2,560.

Even at the top of the range, the proposed price is a fraction of the $50,000 that Wall Street has reportedly come to expect (although RBC analyst Brian Abrahams puts the consensus figure at $11.5K). With critics, including experts on the FDA’s advisory committee, making their fierce opposition to aducanumab’s approval loud and clear, the pricing pressure adds one extra wrinkle Biogen CEO Michel Vounatsos doesn’t need as he orders full-steam preparation for a launch.

'Chang­ing the whole game of drug dis­cov­ery': Leg­endary R&D vet Roger Perl­mut­ter leaps back in­to work as a biotech CEO

Roger Perlmutter needs no introduction to anyone remotely involved in biopharma. As the R&D chief first at Amgen and then Merck, he’s built a stellar reputation and a prolific career steering new drugs toward the market for everything from cancer to infectious diseases.

But for years, he’s also held a less known title: science partner at The Column Group, where he’s regularly consulted about the various ideas the VCs had for new startups.

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