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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

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What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

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Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.
Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

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FDA slaps a hold on an AML tri­al as Mark­er scraps a fail­ing ovar­i­an can­cer pro­gram, sink­ing shares

The FDA has placed a hold on a Phase II AML trial from the small immuno-oncology biotech Marker Therapeutics. Marker disclosed the issue two weeks after responding to FDA concerns, adding it to the Q3 release Tuesday. The company also announced it was scrapping a Phase II ovarian cancer program it determined was unlikely to succeed.

The agency’s concern centers around two reagents used in manufacturing for their trial for acute myeloid leukemia patients who have received a stem cell transplant. The reagents are from third parties and not present in the final product, Marker said.

Eli Lil­ly-backed biotech grabs $100M to dis­patch an­ti­body-oligonu­cleotide con­ju­gates af­ter mus­cu­lar dy­s­tro­phy

Hold up your hand. Make a fist. Now open it. And again.

If you can do it fully and with ease, then the proteins in your hand are likely working properly. If you can’t then they may not be. In people with myotonic muscular dystrophy, something more atomic is going on.

In those folks, the problem is RNA. Certain base pairs repeat far beyond normal, up to 11,000 superfluous letters in some cases. The extended strands form “clumps.” Proteins misform and can’t function properly. They often allow one movement but not the reverse, a condition called myotonia that gives the dystrophy its name.

As­traZeneca sets stage for mar­ket­ing ap­pli­ca­tion with promis­ing piv­otal lu­pus drug da­ta

After fumbling in its first late-stage lupus study, AstraZeneca disclosed that a second pivotal trial testing its experimental drug, anifrolumab, had met the main goal, in August. Earlier this week, the British drugmaker broke out the numbers from its successful study.

Last year, anifrolumab failed to meet the main goal of diminishing disease activity in the 460-patient TULIP I study, a 52-week trial that tested two doses of the drug versus a placebo. But in the 373-patient TULIP II study, the higher dose (300 mg) was compared to patients given a placebo — patients in both arms were on baseline standard care.

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The stakes don’t get much higher, with analysts saying a win this week for Amarin could lead to billions in new sales — provided the agency stamps it with an OK. And investors liked what they say in the FDA review this morning, bumping the stock $AMRN 17%.

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FDA puts Sol­id Bio’s lead gene ther­a­py pro­gram on hold — again — af­ter an­oth­er pa­tient is hurt by SGT-001

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Close to 18 months after the gene therapy biotech was able to quickly shed an FDA hold on their lead Duchenne muscular dystrophy program for SGT-001, regulators have stepped back in to force another halt after another patient was hit hard by a set of serious adverse events remarkably similar to the first set.

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