Mer­ck can’t prove its Alzheimer’s drug works, yet, but it did just ex­plain why it’s spend­ing a for­tune on PhI­II

In­ves­ti­ga­tors for Mer­ck $MRK have very care­ful­ly out­lined all the ear­ly-stage hu­man and an­i­mal da­ta they can muster for their Alzheimer’s drug verube­ce­s­tat. Now in an am­bi­tious Phase III due to read out in mid-2017, tests proved that the BACE drug can suc­cess­ful­ly tar­get one of the key bio­mark­ers for the dis­ease.

They just don’t have any con­vinc­ing da­ta to show whether it will ac­tu­al­ly make a dif­fer­ence in pa­tients’ cog­ni­tive abil­i­ties, or im­prove their abil­i­ty to func­tion in their dai­ly lives.

In many ways, Mer­ck’s case echoes all the up­beat da­ta we’ve heard about Alzheimer’s drugs in re­cent years, and al­so helps ex­plain why this field has been so frus­trat­ing.

First, the da­ta. The key take­away from the ar­ti­cle in Sci­ence Trans­la­tion­al Med­i­cine is that Mer­ck’s drug sig­nif­i­cant­ly re­duced lev­els of amy­loid be­ta in the flu­id sur­round­ing the brain among the ac­tu­al pa­tients tak­ing the drug. Dos­ing was short, with on­ly 32 pa­tients get­ting the drug dai­ly for a week.

That’s not near­ly enough time to de­tect any re­duc­tion in these tox­ic clus­ters by way of a brain scan. And it’s far short of any kind of ev­i­dence that the ther­a­py can ac­tu­al­ly have an im­pact on a dis­ease that dam­ages the brain, per­haps ir­rev­o­ca­bly.

But it does ex­plain why Mer­ck and oth­ers are spend­ing a for­tune on late-stage stud­ies on these BACE drugs.

The mech­a­nism of ac­tion for this drug lies up­stream of amy­loid be­ta. It’s de­signed to in­ter­fere with the pro­duc­tion of amy­loid be­ta, cut­ting the sup­ply of a pro­tein that has be­come one of the chief cul­prits in the dis­ease. Ratch­et down the flow of amy­loid be­ta, the the­o­ry goes, and you can pre­vent the cog­ni­tive and phys­i­cal erup­tions that even­tu­al­ly wipe out a per­son’s mem­o­ry and re­quires care­ful su­per­vi­sion.

The prob­lem with these stud­ies is that com­pa­nies like Mer­ck — and this in­cludes com­pa­nies like Eli Lil­ly, Bio­gen, J&J and many oth­ers — of­ten jump from a Phase I bio­mark­er study in­to broad Phase III stud­ies, look­ing for ev­i­dence that they can bend a re­morse­less dis­ease curve.

Mer­ck al­so in­clud­ed da­ta from its stud­ies in­volv­ing an­i­mals and healthy sub­jects. But aside from pro­vid­ing im­por­tant in­sights on safe­ty, such re­sults rarely mean much of any­thing when it comes to pre­dict­ing ef­fi­ca­cy. But big com­pa­nies are will­ing to over­look big is­sues as they hus­tle in­to late-stage Alzheimer’s tri­als.

Lil­ly was so com­mit­ted to solanezum­ab — which al­so tar­gets amy­loid be­ta — that it mount­ed a new Phase III pro­gram af­ter the last one failed. It al­so re­cent­ly rel­e­gat­ed one key mea­sure on func­tion to a sec­ondary end­point, flag­ging its lack of con­fi­dence on that score.

And most in­ves­ti­ga­tors in the field are mov­ing up­stream in the dis­ease pathol­o­gy, hop­ing to check the dis­ease be­fore it caus­es se­ri­ous dam­age.

De­spite bil­lions spent on new tri­als over the past decade, though, the field has been af­flict­ed by one set­back af­ter the next. Now Mer­ck will take the most ad­vanced study on BACE and help set the stage for a new field in which ri­vals are hus­tling along com­pet­ing ther­a­pies, hop­ing to cash in on one of the biggest un­met med­ical needs in the busi­ness.

Lil­ly will be first up with new Phase III da­ta on solanezum­ab in a mat­ter of weeks. Mer­ck will fol­low in Ju­ly. Some­time over the next year, we’ll be able to un­der­stand much bet­ter just what role amy­loid be­ta plays in Alzheimer’s. And if any­one scores pay dirt da­ta, the pay­off will po­ten­tial­ly be worth bil­lions a year from a new drug fran­chise. Losers will be rel­e­gat­ed to a grow­ing ceme­tery of failed pro­grams.

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

You don’t go more than 40 years in biotech without ever getting a product to market unless you can learn the art of writing a promotional press release. And Inovio captures the prize in baiting the hook.

Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

There was, first and foremost, an interim snapshot of efficacy from their Phase I program for INO-4800.

Jan van de Winkel, Genmab CEO

Seat­tle Ge­net­ics, Gen­mab turn on TV for a high­light reel in cer­vi­cal can­cer — but a ri­val biotech promis­es a bet­ter show

Seattle Genetics $SGEN and their partners at Genmab $GMAB polished up some positive Phase II numbers for their antibody drug conjugate tisotumab vedotin — you can call it TV — for recurrent cervical cancer. And while they mapped out a shortcut to a potential quick approval, the big challenge for this team is being presented by a rival biotech which muscled its way into the spotlight for the same indication a year ago.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Kiniksa preps BLA as Re­gen­eron drug cruis­es to a PhI­II win — shares soar

Kiniksa made a modest $5 million cash bet on Regeneron’s Arcalyst (rilonacept) back in 2017. The startup forged a pact to use the drug, which targets IL-1α and IL-1β, and see how it works against recurrent pericarditis, agreeing to split any profits to come while putting another $27 million in milestones up for grabs.

And the wager paid off handsomely today, as the biotech’s stock surged on their report of a Phase III success that sets up a near-term FDA application. The drug has already won the FDA’s breakthrough drug designation here, heightening expectations of a regulatory success.