It’s over: Eli Lil­ly shares tank af­ter its huge gam­ble on Alzheimer’s drug solanezum­ab ends in fail­ure

Eli Lil­ly CEO John Lech­leit­er

Eli Lil­ly’s mon­u­men­tal ef­fort to prove once and for all that solanezum­ab could work in de­lay­ing Alzheimer’s has end­ed in to­tal fail­ure. The phar­ma gi­ant an­nounced this morn­ing that the drug failed its third Phase III ef­fort at Lil­ly, send­ing its stock in­to a tail­spin.

Back in 2012, in­ves­ti­ga­tors for Lil­ly con­vinced the top ex­ecs at the com­pa­ny that they had seen re­al, tan­gi­ble ben­e­fits for ear­ly-stage pa­tients tak­ing the drug, de­signed to elim­i­nate de­posits of amy­loid be­ta in the brain. The da­ta, they felt, war­rant­ed an­oth­er clin­i­cal odyssey in Phase III, even though that study had failed. And CEO John Lech­leit­er was a stout ad­vo­cate through­out, will­ing to in­vest heav­i­ly in the study. But in the end, the drug of­fered noth­ing but false hope to mil­lions of pa­tients, fail­ing to bend the curve on cog­ni­tive de­clines or the abil­i­ty of pa­tients to func­tion bet­ter.

Lil­ly will take a mod­est $150 mil­lion charge in the fourth quar­ter — just a frac­tion of what it has spent on this drug.

Its shares plunged 14% on the news. And the dam­age ex­tend­ed to oth­er com­pa­nies pur­su­ing the amy­loid be­ta the­o­ry. Bio­gen, which has pro­mot­ed the prospect of ad­u­canum­ab, watched its stock plunge 10% in pre-mar­ket trad­ing. And Ax­o­vant, a com­pa­ny that nabbed a failed Alzheimer’s drug from GSK and put it back in­to the clin­ic, saw its shares drop 18%, even though their drug goes af­ter a com­plete­ly dif­fer­ent tar­get.

The fail­ure here casts a par­tic­u­lar pall over the amy­loid be­ta the­o­ry. The tox­ic pro­tein clus­ters in pa­tients’ brains are con­sid­ered the most like­ly sus­pect for trig­ger­ing the dis­ease, which af­flicts mil­lions. Mer­ck, Bio­gen, Lil­ly and oth­ers all have oth­er pro­grams in the pipeline that look at var­i­ous ways to re­duce the lev­el of amy­loid be­ta in the brain. And those pro­grams will con­tin­ue, along with the de­bate over what tar­gets should be used in fu­ture stud­ies.

Not­ed Leerink’s Sea­mus Fer­nan­dez:

This re­sult will no doubt cast a shad­ow over LLY’s Alzheimer’s Dis­ease (AD) pipeline port­fo­lio, which is heav­i­ly based on the be­ta amy­loid hy­poth­e­sis. Oth­er com­peti­tors’ pro­grams based on this hy­poth­e­sis will prob­a­bly con­tin­ue, but this will like­ly have neg­a­tive read-through on these re­sults in the short term.

The fail­ure at Eli Lil­ly al­so un­der­scores the dis­as­trous record that Alzheimer’s drugs over­all have had in the clin­ic for more than a decade, with a near-uni­ver­sal fail­ure rate. Eli Lil­ly has had one of the longest run­ning R&D ef­forts in Alzheimer’s, with some jaw-drop­ping set­backs along the way. It al­so tried to go af­ter Alzheimer’s with sema­gace­s­tat, on­ly to find that the drug ap­par­ent­ly in­creased the risk of the dis­ease. In­ves­ti­ga­tors and ex­ecs, though, have been steadi­ly lured on by the prospect of mega-block­buster sales, of­ten cru­el­ly tout­ing the po­ten­tial of a ther­a­py, on­ly to ad­mit fail­ure in the end.

“The re­sults of the solanezum­ab EX­PE­DI­TION3 tri­al were not what we had hoped for and we are dis­ap­point­ed for the mil­lions of peo­ple wait­ing for a po­ten­tial dis­ease-mod­i­fy­ing treat­ment for Alzheimer’s dis­ease,” said Lech­leit­er. “We will eval­u­ate the im­pact of these re­sults on the de­vel­op­ment plans for solanezum­ab and our oth­er Alzheimer’s pipeline as­sets.”

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.

Joshua Brumm, Dyne Therapeutics CEO

FDA or­ders DMD tri­al halt, rais­ing ques­tions about a whole class of promis­ing drugs

Dyne Therapeutics’ stock took a nasty hit this morning after the biotech put out word that the FDA had slapped a clinical hold on their top program for Duchenne muscular dystrophy. And now speculation is bouncing around Biotwitter that there could be a class effect at work here that would implicate other drug developers in the freeze.

Dyne execs didn’t have a whole lot to say about why the FDA sidelined their IND for DYNE-251 in DMD while “requesting additional clinical and non-clinical information for” the drug.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Chamath Palihapitiya and Pablo Legorreta

Bil­lion­aires Chamath Pal­i­hapi­tiya and Pablo Legor­re­ta hatch an $825M SPAC for cell ther­a­py biotech

Three years after Royalty Pharma chief Pablo Legorreta led a group of investors to buy up a pair of biotechs and create a new startup called ProKidney, the biotech is jumping straight into an $825 million public shell created by SPAC king and tech billionaire Chamath Palihapitiya.

ProKidney was founded 6 years ago but really got going at the beginning of 2019 with the $62 million acquisition of inRegen, which was working on an autologous — from the patient — cell therapy for kidney disease. After extracting kidney cells from patients, researchers expand the cells in the lab and then inject them back into patients, aiming to restore the kidneys of patients suffering from CKD.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Ciaran McCrickard)

An un­ortho­dox pro­pos­al for Bio­gen's Medicare-man­dat­ed Aduhelm tri­al

Biogen has gone full blitz since Medicare announced it would only cover its new Alzheimer’s drug when used in clinical trials, accusing the agency of discriminating against Alzheimer’s patients and trying to get physicians to change regulators’ minds.  Critics, meanwhile, cheered what they see as a necessary wall protecting payers and patients from an unproven and unsafe drug.

Far less attention, though, has gone to what a Medicare-funded clinical trial would actually look like. Biogen has operated as if it would be a standard late-stage Alzheimer’s trial, enrolling a couple thousand patients and giving half placebo.

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