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.

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine -- so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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FDA hands Mor­phoSys and In­cyte a quick OK on their po­ten­tial block­buster CAR-T al­ter­na­tive

Nearly three years after okaying the CAR-Ts Yescarta and Kymriah, the FDA has approved a new CD19 therapy.

MorphoSys’ Monjuvi, or tafasitamab-cxix, was cleared Friday for use in refractory diffuse large B-cell lymphoma (DBLCL). The approval sets up both MorphoSys and their commercial partner Incyte to compete with Gilead and Novartis in the ultra-competitive indication, where similar trial results and far easier delivery could allow them to cut a fair share of the market.

So Covid-19 leader BioN­Tech has a can­cer vac­cine in de­vel­op­ment? Yes, and Re­gen­eron just jumped in for the PhII com­bo study

Before the coronavirus global emergency stole the R&D show in biopharma, the leaders in the race to develop new mRNA therapies had a big interest in determining if their tech could be used to create an effective cancer vaccine after all the first-gen tries had failed to impress. So perhaps it’s not surprising that an early cut of the data at frontrunner BioNTech went largely unnoticed.

Unless you were at Regeneron.

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No­var­tis says Kym­ri­ah reach­es pri­ma­ry end­point in new PhII, al­though num­bers still to come

The race to develop CAR-T therapies has died down since Novartis’ Kymriah and Gilead’s Yescarta first crossed the finish line, though Tecartus also recently received approval. But the companies continue to expand their drugs’ applications, with Novartis preparing to conclude a new Phase II.

Interim data announced by the Swiss pharma show that Kymriah met its primary endpoint of complete response rate in treating patients with relapsed or refractory follicular lymphoma, the second-most common form of non-Hodgkin lymphoma. Based on preliminary trial findings, Kymriah had received RMAT designation from the FDA in April for r/r follicular lymphoma.

Ab­b­Vie shrugs off $134M cash deals, quit­ting a neu­ro R&D pact with Voy­ager Ther­a­peu­tics on vec­tor­ized an­ti­body treat­ments

It’s the end of the road for Voyager Therapeutics’ collaboration with AbbVie on tau and alpha-synuclein vectorized antibody development.

In two deals spanning the last two years, AbbVie dropped more than $134 million upfront for Voyager’s preclinical R&D of vectorized antibody treatments for diseases like Alzheimer’s and Parkinson’s. But Voyager says AbbVie is walking away now, without offering an explanation for why.

Mer­ck scoops up a PhII J&J dis­card in a bar­gain-base­ment deal. And this time they’re shoot­ing at NASH

When J&J turned to South Korea’s Hanmi for a GLP-1/glucagon dual receptor agonist obesity drug, the pharma giant paid $105 million in a cash upfront for the licensing rights and plotted a big clinical trial program to test it. A year ago, like a few of Hanmi’s big partners, J&J reviewed their trial data and walked away, handing it back.

Now Merck is stepping up to grab it for their NASH pipeline — and they got it a lot cheaper than J&J.

Igor Splawski (CureVac)

Cure­Vac nabs a top No­var­tis sci­en­tist for CSO slot as mR­NA vac­cines seize the spot­light

One of the key players in the race to develop a new mRNA vaccine to fight Covid-19 has reshuffled the top spots in the executive suite. And they’re bringing in a Novartis vet out of Harvard to spearhead their work on mRNA.

CureVac, which just filed for an IPO that’s still taking shape, has formally handed Franz-Werner Haas the CEO title, after giving it to him on an interim basis. And the still rather stealthy German biotech largely owned by billionaire Dietmar Hopp has recruited Igor Splawski as its chief scientific officer.

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