PhI­II Alzheimer’s drug goes bust — and a ma­jor set­back at Eli Lil­ly and As­traZeneca may doom the class

An­oth­er big Phase III Alzheimer’s pro­gram is be­ing scrapped at Eli Lil­ly $LLY and As­traZeneca $AZN, of­fer­ing fresh ev­i­dence that the en­tire BACE class may be com­plete­ly use­less in slow­ing or pre­vent­ing the dis­ease in symp­to­matic pa­tients.

Dan Skovron­sky

The drug this time is lan­abece­s­tat, which Lil­ly grabbed close to 4 years ago in a $500 mil­lion pact with As­traZeneca — a mod­est $50 mil­lion in cash. At the time, Lil­ly was plug­ging a gap in its Alzheimer’s pipeline af­ter the fail­ure of its own BACE ef­fort due to tox­i­c­i­ty is­sues with that par­tic­u­lar med­ica­tion.

This time, fin­gers are point­ing to the en­tire class in a flop that will like­ly cause fresh angst over a huge ques­tion: Is amy­loid be­ta re­al­ly the cul­prit here?

The BACE the­o­ry is easy enough to un­der­stand. Mov­ing up­stream in the bi­o­log­i­cal process for the pro­duc­tion of amy­loid be­ta, re­searchers hoped to bend the course of the dis­ease by clos­ing the tap on tox­ic pro­teins. Mer­ck was the first to try it in a pair of Phase III stud­ies and sim­ply con­clud­ed it was a bust, prob­a­bly on­ly the­o­ret­i­cal­ly use­ful now in pre-symp­to­matic pa­tients or as a com­bo.

Eli Lil­ly will now move to shut­ter two big tri­als — the AMA­RANTH tri­al, in ear­ly Alzheimer’s dis­ease, and the DAY­BREAK-ALZ tri­al, in mild Alzheimer’s dis­ease de­men­tia — af­ter the mon­i­tor­ing com­mit­tee called it on fu­til­i­ty.

The fail­ure of Lil­ly and As­traZeneca’s drug may sound the death knell on a so­lo BACE strat­e­gy in ear­ly and mild pa­tients, even though Bio­gen just tout­ed its Phase II BACE study herald­ing the bio­mark­er suc­cess on amy­loid be­ta along­side an ab­sence of a sta­tis­ti­cal­ly sig­nif­i­cant im­pact on cog­ni­tion — much the same as what Mer­ck was track­ing.

In lan­abece­s­tat’s case, we on­ly know that the drug ap­peared safe and in­ef­fec­tive, no hard da­ta are avail­able yet.

Why keep try­ing af­ter more than a decade of fail­ures? As­traZeneca an­swered that ques­tion when Pas­cal So­ri­ot once es­ti­mat­ed that this drug could earn $5 bil­lion a year. 

That’s not go­ing to hap­pen, of course. But de­vel­op­ers keep ham­mer­ing away at it — even as big play­ers re­main puz­zled about what caus­es the dis­ease. 

Fol­low­ing the fail­ure of solanezum­ab in three straight piv­otal stud­ies, Eli Lil­ly doesn’t have much of a cred­i­ble pipeline left in the field. And af­ter Pfiz­er bowed out fol­low­ing big re­treats at GSK and As­traZeneca, Big Phar­ma may be do­ing some ad­di­tion­al soul search­ing about its role in R&D. Lil­ly, though, vows to sol­dier on af­ter spend­ing bil­lions on fail­ure.

“Lil­ly re­mains ded­i­cat­ed to Alzheimer’s dis­ease re­search as we have been for the last three decades,” says R&D chief Daniel Skovron­sky. “We won’t give up on find­ing a so­lu­tion for Alzheimer’s pa­tients.”

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.

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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In­vestors could emerge from Neil Wood­ford de­ba­cle with £1B loss, in­ter­nal analy­sis re­veals

When Link Fund Solutions announced that it is closing Woodford Equity Income Fund permanently and kicking out Neil Woodford, it was implied that investors probably won’t get back everything they entrusted to the fund manager. But nobody knew just how much they would lose.

An internal analysis commissioned by Link suggested that the collective loss could amount to £1 billion — out of a fund last valued at £3.1 billion — Citywire has revealed.

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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Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

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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FDA Vas­cepa re­view spot­lights new safe­ty sig­nals, pos­si­ble min­er­al oil spoil­er as Amarin hunts a block­buster ap­proval

An in-house FDA review of Amarin’s Vascepa raises a set of hurdles the biotech will have to clear if the biotech expects to get the long-awaited FDA approval that could set it on a path to superstar status. But it appears that Amarin has survived another potential setback without introducing a major new threat to its prospects.

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

Solid Biosciences continues to be plagued by safety issues.

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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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.