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.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Large advertisements for the drug Vivitrol decorate the walls of Grand Central Station on June 15, 2017 in New York City. (Photo: Andrew Lichtenstein via Getty)

FDA slaps down Alk­er­mes for mis­lead­ing Viv­it­rol ads — don't for­get vul­ner­a­bil­i­ty to opi­oid over­dose

The ads piqued interest as soon as they started appearing in 2016: at Grand Central Station, on the Red Line in Cambridge, and on a billboard off the New Jersey Turnpike. All showed a young person, generally with his or her arms crossed, and the question, “what is Vivitrol?”

Vivitrol’s maker, Alkermes, was in the midst of a marketing and lobbying campaign to promote the anti-opioid addiction drug — a campaign that would face significant backlash for tarnishing competitors despite little evidence for Vivitrol’s superiority.

Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house review highlights a disagreement of investigators’ use of a key endpoint by Horizon Pharma in the late-stage trial for the top drug in its pipeline, but largely agreed that the antibody was effective.

Horizon submitted a BLA for thyroid eye disease (TED) drug teprotumumab in March, less than two years after they bought the drug (and the rest of a division) from Narrow River for $145 million upfront. With breakthrough status, priority review, orphan designation and in-house sales projections of up to $750 million, the one-time Roche reject became the marquee pipeline asset for a company that’s developed some of the world’s most expensive drugs.

Seat­tle Ge­net­ics de­tails pos­i­tive OS and PFS da­ta for tu­ca­tinib in breast can­cer

Seattle Genetics $SGEN is showing off more positive data around tucatinib, its pivotal-stage drug for HER2 positive breast cancer.

A month after hearing about solidly upbeat hazard ratios, we learned today that the estimated progression-free survival rate at one year was 33% in the tucatinib arm compared to 12% for patients taking trastuzumab and capecitabine alone.

Median PFS was 7.8 months (95% CI: 7.5, 9.6) in the tucatinib arm, compared to 5.6 months (95% CI: 4.2, 7.1) in the control arm.

Bat­tered, cash hun­gry In­tec feels the burn of No­var­tis re­jec­tion

It’s a case of some bad timing for Intec.

Just when a key trial testing the company’s Accordion drug delivery tech imploded in Parkinson’s disease, they handed Novartis data from a successful PK study of a custom Accordion pill engineered to deliver a Novartis compound to entice the Swiss drugmaker into signing a licensing agreement.

Novartis said thanks, but no thanks.

For the cash-strapped Israeli drug developer, the failure to clinch the deal marks a big blow. As of the third quarter, the company has $15.7 million in cash and equivalents, which HC Wainwright analysts estimate will keep the lights on into mid-2020.

Bris­tol-My­ers shows off a low-pro­file AML con­tender it gained from Cel­gene buy­out — and they’re tak­ing it straight to the FDA

Bristol-Myers Squibb reaped an enormous pipeline with its much-criticized $64 billion megadeal to buy Celgene. And it got a few hidden gems in the deal.

One of those gems was brought out for display on Tuesday, with a late-breaker at ASH on CC-486, which is now being prepped for regulatory filings at the FDA and elsewhere.

Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come.

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