Mer­ck’s lead­ing PhI­II BACE drug im­plodes in lat­est Alzheimer’s dis­as­ter

Roger M. Perl­mut­ter, Mer­ck

Scratch yet an­oth­er Phase III Alzheimer’s drug hope­ful.

Mer­ck $MRK an­nounced late Tues­day that it is shut­ter­ing its EPOCH tri­al for the BACE in­hibitor verube­ce­s­tat in mild-to-mod­er­ate Alzheimer’s af­ter the ex­ter­nal da­ta mon­i­tor­ing com­mit­tee con­clud­ed that the drug was a bust, with “vir­tu­al­ly” no chance of suc­cess. A sep­a­rate Phase III study in pro­dro­mal pa­tients, set to read out in two years, will con­tin­ue as in­ves­ti­ga­tors found no signs of safe­ty is­sues.

This is one of Mer­ck’s top late-stage drugs, and news of the fail­ure drove down the phar­ma gi­ant’s shares in af­ter-mar­ket trad­ing by 2.45%.

BACE drugs es­sen­tial­ly seek to in­ter­fere in the process that cre­ates amy­loid be­ta, a tox­ic pro­tein of­ten found in the brains of Alzheimer’s pa­tients. As the top amy­loid be­ta drugs like bap­ineuzum­ab and solanezum­ab — which sought to ex­tract ex­ist­ing amy­loid be­ta loads — ground their way to re­peat­ed fail­ures, de­vel­op­ers in the field turned in­creas­ing­ly to BACE ther­a­pies as an al­ter­na­tive mech­a­nism that could pro­vide the key to slow­ing this dis­ease down.

Mer­ck’s ef­fort was the most ad­vanced in the pipeline, but Eli Lil­ly $LLY and oth­ers are still in hot pur­suit with their own per­sis­tent BACE ef­forts. Teams from Bio­gen/Ei­sai and No­var­tis/Am­gen are al­so beaver­ing away on BACE.

“Alzheimer’s dis­ease is one of the most press­ing and daunt­ing med­ical is­sues of our time, with in­her­ent, sub­stan­tial chal­lenges to de­vel­op­ing an ef­fec­tive dis­ease-mod­i­fy­ing ther­a­py for peo­ple with mild-to-mod­er­ate dis­ease. Stud­ies such as EPOCH are crit­i­cal, and we are in­debt­ed to the pa­tients in this study and their care­givers,” said Dr. Roger M. Perl­mut­ter, pres­i­dent, Mer­ck Re­search Lab­o­ra­to­ries. “While we are dis­ap­point­ed that a ben­e­fit was not ob­served in this study, our work con­tin­ues with APECS, which is study­ing verube­ce­s­tat in peo­ple with less ad­vanced dis­ease.”

Lil­ly re­cent­ly de­cid­ed to go ahead and stop its own prodomal Phase III for solanezum­ab af­ter con­clud­ing that there was no log­i­cal rea­son to be­lieve it could suc­ceed af­ter the study in pa­tients with a mild form of the mem­o­ry-wast­ing dis­ease end­ed in dis­as­ter.

No sig­nif­i­cant new drug for Alzheimer’s has been ap­proved in the past 14 years, de­spite mas­sive­ly ex­pen­sive tri­als aimed at tack­ling the dis­ease. The pipeline has been lit­tered with big fail­ures, which have come in a steady drum­beat of de­feat and dis­cour­age­ment.

Cu­ri­ous­ly, the next Phase III in Alzheimer’s to read out will be­long to Ax­o­vant $AX­ON, a start­up from Vivek Ra­maswamy, who bought in a failed drug from GSK and put it back in­to the clin­ic. Their 5-HT6 ther­a­py fol­lows a se­ries of fail­ures in the field for drugs that aimed at amp­ing up cog­ni­tion. The next big drug in the clin­ic — ad­u­canum­ab — be­longs to Bio­gen $BI­IB, which has stirred some sig­nif­i­cant ex­pec­ta­tions for a ther­a­py that al­so has a trou­bling safe­ty his­to­ry.

A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Su­per-se­cre­tive an­ti-ag­ing biotech Cal­i­co tees up the first vis­i­ble clin­i­cal tri­al of an ex­per­i­men­tal drug. And it’s for can­cer?

Over the past 7 years, Calico has been so much more than your average, run-of-the-mill secretive biotech players. It’s a riddle, wrapped in a mystery, inside an enigma, to repurpose an old Winston Churchill line dating from the time he confronted the Iron Curtain surrounding Stalin’s thoughts.

Launched by industry legend Art Levinson of Genentech fame, with the infinitely deep pockets of Google for support, one of the few big headlines the anti-aging biotech has sparked focused on a major alliance with AbbVie — a giant outfit that conversely likes to show off its drug prospects whenever it can. Together, they’ve been focused on diseases that limit life span — quite an arc of ailments.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Af­ter near­ly a year of de­bate, the Covid-19 vac­cine chal­lenge tri­als are of­fi­cial­ly com­ing

After nearly a year of public advocacy and often rancorous ethical debate, human challenge trials for Covid-19 vaccines are getting off the ground in London.

The UK government’s Covid-19 Vaccine Taskforce and the contract research firm Open Orphan announced today £10 million ($13 million) plan to test experimental Covid-19 vaccines in volunteers whintentionally exposed to the novel coronavirus. The studies, which won’t launch until early 2021, come after 9 months of debate over whether such studies were safe and would actually hasten vaccine development, and they follow a long history of researchers using challenge models to study other respiratory viruses, including flu and the coronaviruses that cause the common cold.

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Derek Chalmers, Cara Ther

Cara lines up a $440M deal for US rights to its late-stage drug for se­vere itch, with $150M cash on the ta­ble

With plans afoot to file an NDA for what could be its first approved drug, Cara Therapeutics is pivoting its focus to commercialization. And Swiss company Vifor Pharma is willing to surrender up to $440 million to market the candidate in the US.

Cara $CARA CEO Derek Chalmers said an NDA submission is coming this quarter for their intravenous drug Korsuva in chronic kidney disease-associated pruritus (CKD-aP), a severe itching condition. The Stamford, CT-based biotech read out positive topline data from a Phase III pivotal study back in April, and announced plans to approach EMA regulators shortly after filing with the FDA.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Gilead feels the heat as close al­ly Gala­pa­gos re­ports a big set­back on one of their top ex­per­i­men­tal drugs

The bad news keeps stacking up at Galapagos — which quite likely just lost control of a billion-dollar deal — and by extension their close partners at Gilead.

The biotech $GLPG reported after the bell Thursday that GLPG1972, one of their top development programs, flat failed a mid-stage study for osteoarthritis, flunking the primary and all secondary endpoints.

Testing 3 different doses of their drug, which relies on ADAMTS-5 inhibition, investigators concluded that none of them triggered a statistically significant response — as measured by cartilage thickness.

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Covid-19 roundup: Pars­ing Bourla, a top an­a­lyst sees im­proved chances for Pfiz­er vac­cine; Fau­ci: No sur­prise that Trump was hit by Covid-19

With a medley of adverse events hobbling the late-stage development of vaccines and drugs, Pfizer CEO Albert Bourla’s latest — extended — timeline for the mRNA approach they’re working on with BioNTech is giving some top analysts added confidence that the pharma giant can come up with the regulatory goods next month.

Parsing Bourla’s language in his comments last week, SVB Leerink’s Geoffrey Porges notes that Bourla’s decision to say they “may” be able to nail down the positive efficacy of their vaccine in a matter of days — a big change from his earlier certainty — may also indicate a delay on that to early November.

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Mer­ck touts new da­ta for Keytru­da com­bos in NSCLC at North Amer­i­can con­fer­ence

Merck marched out new data from two studies on Friday to back king Keytruda — the drug that made the Big Pharma $11.1 billion last year — in advanced non-small cell lung cancer (NSCLC).

At the IASLC 2020 North America Conference on Lung Cancer, Merck read out long-term data from Cohort G of its Keynote-021 study, which assessed Keytruda in combination with chemotherapy. It also touted results from a Phase I/II study testing Keytruda and quavonlimab, its anti-CTLA-4 therapy, as a first-line therapy.

IN8bio CEO William Ho (IN8bio)

Bring­ing their ge­net­i­cal­ly mod­i­fied gam­ma delta T cells to Nas­daq, IN8bio files for $86M IPO

The biotech IPO parade continues marching forward as 2020 turns toward the fourth quarter.

IN8bio, a New York-based company focused on genetically modified gamma delta T cell therapies, filed to go public Friday seeking an $86 million raise. The company has two clinical-stage candidates being studied in glioblastoma and leukemia, respectively.

By any stretch of the imagination, 2020 has already been a huge year for biotech, and nowhere does it appear more obvious than the vast amounts of companies hitting the public market.