Bio­gen hy­pes a fresh set of ear­ly, up­beat re­sults for Alzheimer’s drug

New da­ta from an ear­ly-stage study of Bio­gen’s Alzheimer’s drug ad­u­canum­ab has demon­strat­ed a clear im­pact on de­posits of amy­loid be­ta, the tox­ic tan­gles in the brain sus­pect­ed of trig­ger­ing the mem­o­ry-wast­ing ail­ment. And while they couldn’t pre­cise­ly prove it, the re­searchers spot­light­ed ad­di­tion­al ev­i­dence that the drug might al­so be slow­ing the steady cog­ni­tive de­cline of the peo­ple tak­ing the drug.

Al San­drock, Bio­gen Chief Med­ical Of­fi­cer

The ev­i­dence — a de­tailed re­tread of re­sults that have al­ready been re­viewed — im­me­di­ate­ly trig­gered the kind of re­lent­less hype that has sur­round­ed ad­u­canum­ab from the first ear­ly signs of its abil­i­ty to have an im­pact on the dis­ease. But there are some im­por­tant caveats that en­thu­si­asts nev­er­the­less need to keep in mind.

First, while amy­loid be­ta de­posits are a well de­fined tar­get, it’s al­so not uni­ver­sal­ly ac­cept­ed as the sole cause of Alzheimer’s. There are some who be­lieve it may not be in­volved at all, point­ing to pa­tients who have the clus­ters in their brains but no symp­toms of de­men­tia. In ad­di­tion, the re­searchers care­ful­ly not­ed that the study with 165 pa­tients was not pow­ered to pro­vide clear ev­i­dence of ef­fi­ca­cy.

The en­thu­si­asm among the ex­ecs and re­searchers in­volved, though, was pal­pa­ble. And Bio­gen, which bad­ly needs to whip up some ex­cite­ment for the com­pa­ny’s pipeline, was not in the least bit re­luc­tant to pump the lat­est da­ta set that has now been pub­lished in Na­ture. Chief Med­ical Of­fi­cer Al San­drock re­marked:

“These ear­ly stud­ies of ad­u­canum­ab show its ef­fec­tive­ness in re­mov­ing amy­loid plaque from the brain as well as its po­ten­tial ef­fect on the slow­ing of cog­ni­tive de­cline in pa­tients suf­fer­ing from Alzheimer’s dis­ease. Pub­li­ca­tion in Na­ture is an achieve­ment we share with the many sci­en­tists and clin­i­cal in­ves­ti­ga­tors who con­duct­ed this re­search as well as the pa­tients who vol­un­teered to par­tic­i­pate in our clin­i­cal tri­al; we are grate­ful to all of them.”

There is, how­ev­er, a long way to go from a suc­cess­ful Phase Ib study to a piv­otal win, which is where Bio­gen is now fo­cused.

Shares of Bio­gen re­mained down slight­ly for the day.

In ad­di­tion to the pos­i­tive signs that the high dose was most ef­fec­tive, there were al­so some con­cerns.

Check­ing on safe­ty, 38% of the pa­tients in the high, 10 mg kg arm of the study dropped out, many cit­ing side ef­fects, com­pared to 25% of the place­bo arm.

Bio­gen’s progress on Alzheimer’s has helped whip up fresh en­thu­si­asm for the amy­loid be­ta hy­poth­e­sis, even spurring Roche to keep one of its failed drugs, gan­tenerum­ab, in the pipeline. Sev­er­al late-stage drugs, in­clud­ing solanezum­ab at Eli Lil­ly, al­so at­tack a-be­ta, look­ing to prove their ef­fec­tive­ness in very ear­ly-stage pa­tients, be­fore the dis­ease caus­es se­ri­ous brain dam­age. New imag­ing tech­niques are al­so bet­ter able to iden­ti­fy pa­tients who are most like­ly to ben­e­fit.

Lil­ly is ex­pect­ed to de­liv­er piv­otal da­ta from its sec­ond Phase III pro­gram lat­er in the year. But it’s al­so been back­ing away from a key end­point on dai­ly func­tion, sig­nal­ing that it ex­pects to be able to prove an im­pact on cog­ni­tion.

Bio­gen, mean­while, is see­ing off CEO George Scan­gos at a time the biotech com­pa­ny has been un­der heavy pres­sure to do some­thing now to prove it has im­por­tant new drugs in the pipeline that can make up for flag­ging sales of its flag­ship drug, Tec­fidera. Still some ways from their piv­otal read out, and un­able so far to come up with the kind of deal that can gen­er­ate some cheers from Wall Street an­a­lysts, Bio­gen will set­tle for trum­pet­ing an­oth­er ear­ly snap­shot for ad­u­canum­ab.

Jef­feries’ Bri­an Abra­hams not­ed:

Much of the clin­i­cal de­tails, sub-analy­ses and pre­clin­i­cal da­ta have all been ex­ten­sive­ly pre­sent­ed, and we didn’t de­tect any­thing ma­te­ri­al­ly new in the ar­ti­cle; it did cite cau­tion in in­ter­pret­ing cog­ni­tive end­points giv­en lack of pow­er­ing for these mea­sures and no im­pu­ta­tion for miss­ing val­ues, and point­ed out the pos­si­bil­i­ty the need for MRIs in pa­tients de­vel­op­ing ARIA could have un­blind­ed the study. Still, the dose-de­pen­dent plaque re­duc­tions and cor­re­la­tion be­tween plaque clear­ance and cog­ni­tive ben­e­fits con­tin­ue to look most com­pelling to us, and we con­tin­ue to see a 45% prob­a­bil­i­ty of ul­ti­mate­ly gen­er­at­ing $2B+ rev­enues to BI­IB by 2025.


5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

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What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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With patent con­cerns loom­ing, Roche gets a new pri­or­i­ty re­view on block­buster IPF drug

Seven years after the FDA first approved Esbriet, the blockbuster Roche IPF drug is getting an expedited review for a second indication.

On Thursday, the agency gave Esbriet priority review for unclassified interstitial lung diseases, or forms of pulmonary inflammation and scarring that don’t fit easily into the over 200 known types of ILD. The move comes 10 months after Esbriet received breakthrough designation and sets Roche up for a decision by May.

Michelle McMurry-Heath, BIO CEO (BIO via YouTube)

BIO looks to re­struc­ture, lay­ing off staff amid chal­lenge to the trade org's nor­mal face-to-face style

The biopharma industry, on the whole, had a red-letter year in 2020 amid Covid-19, with fundraising at an all-time high and major players speeding vaccines ahead to approval. But for BIO, the industry’s leading trade organization, the pandemic has prompted a reconsideration of the game plan.

BIO will pivot to digital as the Covid-19 pandemic continues to rage, making “some staff reductions” as it looks to bring its roughly 37,000 in-person meetings each year to the web, the organization said Thursday.

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Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

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Covid-19 roundup: Italy won­ders aloud if it can sue Pfiz­er for vac­cine short­falls; Flood, dead­ly fire threat­en As­traZeneca vac­cine plants,

As reports crop up that deliveries of Pfizer and BioNTech’s Covid-19 vaccine are being unexpectedly cut, Italy wonders if it can take the vaccine developers to court, according to the Wall Street Journal. 

After its shipment for this week was cut by 29%, the Italian government consulted its attorney general about taking legal action, the WSJ reported. Pfizer and BioNTech had warned the EU and Canada last week that their allocations would be reduced as Pfizer upgrades its Belgium factory. What Italy says it doesn’t appreciate, though, is the short notice.