Neu­rotrope this week joined the long line of bio­phar­ma com­pa­nies that have been mauled by clin­i­cal fail­ure for Alzheimer’s drugs. But their crushed shares ($NTRP down from more than $8 in June to pen­ny stock range to­day) rep­re­sent­ed just a tiny drop in the buck­et of red ink that has drained from play­ers which have pur­sued the great­est of all Holy Grails in drug R&D. Decades of de­feat, head­lined by the likes of solanezum­ab at Eli Lil­ly stretch­ing to the most re­cent sna­fu with Bio­gen’s ad­u­canum­ab, have forced a slew of play­ers to change course on their R&D strat­e­gy — or just leave it in lim­bo.

How bad is it?

Bio­gen’s shares tanked when ad­u­canum­ab bombed, forc­ing an ear­ly halt to the late-stage ef­fort. The mar­ket cap shriv­eled by bil­lions, and it’s still down about 29% from pre-cri­sis lev­els. That plunge came af­ter Roche’s crenezum­ab flopped, though Roche was much bet­ter po­si­tioned to han­dle the fail­ure. But its part­ner, AC Im­mune $ACIU saw its share price halved in the fall­out.

The field went over the cliff in 2019.

What makes this im­por­tant for the long run?

In­vestors and an­a­lysts don’t gen­er­al­ly care to en­ter a mine­field where the chance of be­ing blown sky-high has been run­ning 100% — a mes­sage that has been heard loud and clear in re­cent months. Bio­gen — still al­lied to Ei­sai — has es­sen­tial­ly been ad­vised to write off Alzheimer’s al­to­geth­er as a com­plete loss. The amy­loid hy­poth­e­sis lies in tat­ters, while a se­ries of BACE fail­ures al­so un­der­scored some trou­bling safe­ty is­sues that made it all the way in­to a se­ries of late-stage stud­ies.

No one here re­al­ly knows what they’re do­ing. And any new rounds of mid-stage da­ta claim­ing suc­cess against bio­mark­ers are wide­ly ig­nored. Be­cause the bio­mark­ers have nev­er been proven to be in­dica­tive of suc­cess.

And with­out in­vestor sup­port, you can for­get any ma­jor new for­ays in late-stage test­ing.

The fo­cus now has shift­ed to tau and com­bo ther­a­pies, as new com­pa­nies start to tout ques­tion­able ev­i­dence of “suc­cess” in or­der to try to lure in­vestors back. But af­ter you’ve been burned this many times, that ar­gu­ment will be hard to make.

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.

ICER, an increasingly influential cost-effectiveness watchdog in the United States, has concluded in its review of treatments for cardiovascular disease that while the cost of J&J’s Xarelto and Amarin’s Vascepa meet its benchmark for value pricing — the two treatments will not likely treat as many patients as hoped without surpassing the annual budget threshold calculated by ICER for each therapy.