RIP amy­loid be­ta the­o­ry? Nope. Bio­gen part­ner launch­es a new PhI­II be­fore ad­u­canum­ab's corpse turned cold

A day af­ter Bio­gen rat­tled the bio­phar­ma world with the news that its lead late-stage ther­a­py ad­u­canum­ab proved worth­less in treat­ing Alzheimer’s — a dis­as­ter that may dri­ve a stake through the heart of the amy­loid be­ta the­o­ry once and for all — the big biotech’s part­ners at Ei­sai have come up with their next big move.


Right in the wake of a 35% plunge in their stock val­ue, Ei­sai $ESALY is start­ing a Phase III study in­volv­ing 1,566 Alzheimer’s pa­tients with mild cog­ni­tive im­pair­ment for the con­tro­ver­sial Alzheimer’s drug BAN2401. The an­ti-amy­loid an­ti­body was the cen­ter of a firestorm of crit­i­cism over a tardy re­veal that re­searchers had pulled high-risk pa­tients out of their last study, po­ten­tial­ly warp­ing the pos­i­tive re­sults that were claimed, leav­ing that drug un­der a dark cloud.

“We still be­lieve that amy­loid be­ta hy­poth­e­sis is po­ten­tial­ly the right ap­proach for the treat­ment of Alzheimer’s dis­ease,” an Ei­sai spokesman told Reuters.

That’s a po­si­tion that Bio­gen ex­ecs will find tough to jus­ti­fy to­day. A whole slate of ma­jor de­vel­op­ers — Eli Lil­ly and As­traZeneca, Mer­ck and Roche — have re­port­ed out de­ci­sive late-stage fail­ures over the last year that all point to one con­clu­sion: Tar­get­ing amy­loid be­ta alone in symp­to­matic pa­tients may hit your bio­mark­ers on ef­fect, but it doesn’t de­lay the ruth­less march of the dis­ease.

Ei­sai and Bio­gen may not have re­ceived the memo, but a whole host of an­a­lysts have writ­ten off BAN2401 as a los­er. As for this new move, don’t ex­pect any sup­port from Leerink’s Ge­of­frey Porges, who es­sen­tial­ly be­lieves any new work like this is dam­ag­ing to in­vestors and pa­tients. He not­ed this morn­ing:

We as­sume that the com­pa­ny (Bio­gen) takes the re­spon­si­ble de­ci­sion to ter­mi­nate all fur­ther in­vest­ments in be­ta amy­loid-di­rect­ed med­i­cines (which has not oc­curred), and saves their in­vestors the cash and saves pa­tients and in­ves­ti­ga­tors from the bur­den of such stud­ies. If Bio­gen does not make this de­ci­sion, then our ad­just­ed ex­pense fore­cast could be too low, with fur­ther neg­a­tive ef­fects on our val­u­a­tion even com­pared to our new PT.

What will be ahead for Bio­gen? Porges is tak­ing a hard line. It’s worth quot­ing him at length.

In our view, Bio­gen finds it­self in the un­en­vi­able po­si­tion of be­ing a wound­ed cash cow (which we are sur­prised man­age­ment and the board did not con­sid­er as a po­ten­tial out­come and pre­pare for). The next few months are like­ly to con­sist of a mix­ture of re­crim­i­na­tions, ex­pla­na­tions, ne­go­ti­a­tions, and pos­si­bly ter­mi­na­tions and lit­i­ga­tion. We ex­pect the com­pa­ny to be dis­tract­ed and ham­pered by those over­hangs for a cou­ple of quar­ters at least. Con­trary to pop­u­lar be­lief we don’t be­lieve that their board or man­age­ment will have the lat­i­tude to im­me­di­ate­ly piv­ot to ma­jor ac­qui­si­tions that would al­ter the com­pa­ny’s out­look ma­te­ri­al­ly (de­spite our sug­ges­tions in the past that such in­vest­ments were ad­vis­able). To­ward the end of this year, af­ter the dust of this dis­ap­point­ment has like­ly set­tled, we ex­pect Bio­gen to ex­plore both as­set sales and as­set pur­chas­es (af­ter oth­er changes have been made, or im­posed by in­vestors). We be­lieve that the case for re­struc­tur­ing and di­vesti­tures will be as com­pelling as the case for ac­qui­si­tions, par­tic­u­lar­ly in the con­text of such poor re­turns from the com­pa­ny’s re­cent cap­i­tal al­lo­ca­tion de­ci­sions.

Bio­gen shares $BI­IB tum­bled 29% on Thurs­day, wip­ing out $18 bil­lion in mar­ket cap. They won’t get any of that back based on the launch of the BAN2401 tri­al. To the con­trary. At a time they need to re­build con­fi­dence, there’s no sign that the part­ners learned any­thing this week.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

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Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.

Photo: Shutterstock

Bio­phar­ma's suc­cess rate in bring­ing drugs to mar­ket has long been abysmal. Can new tools help rewrite that trou­bled past?

In 2011, a team of researchers at British drugmaker AstraZeneca had a problem they were looking to solve.

For years, drug discovery and development were a wasteland for innovation. Novel drugs largely fell into one of two categories — monoclonal antibodies and small molecules — and new therapeutic modalities were hard to come by. After a rush of promising approvals in the late 1990s — including then-Biogen’s CD20 targeting antibody breakthrough Rituxan — the field stagnated and attrition rates stayed sky-high. What exactly is the industry doing wrong? AstraZeneca asked itself.

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