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.

The 20 un­der 40: In­side the next gen­er­a­tion of bio­phar­ma lead­ers

“Each generation needs a new music,” Francis Crick wrote in 1988, reflecting back on his landmark discovery. Crick was 35, then, in 1953, when he began working with a 23-year-old named James Watson, and 37 when the pair unveiled the double helix. Rosalind Franklin, whose diffraction work undergirded their metal model, was 32.

The model would become the score for a new era in biology, one devoted to cracking the basic structures turning inside life. Subsequent years would bring new conductors and new rhythms: Robert Swanson, 29 when he convinced a 39-year-old Herb Boyer to build a company off his work and call it Genentech; Phillip Sharp, 29 when he discovered RNA splicing and 34 when he co-founded Biogen; Frances Arnold, 36 when she pioneered directed evolution; Feng Zhang, 31 when he published his CRISPR paper.

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Chart-top­ping ven­ture cash? Strong deal flow? In the month Covid-19 ripped around the globe? Yup

It turns out that even sending everyone from the CEO to rank-and-file staffers home to work in the middle of a Category 5 pandemic wasn’t enough to put a crimp in the flow of venture cash into biopharma. And even dealmaking held its own against the howling winds of misfortune — largely because a group of savvy players was quick to adjust to the new reality.

Our deal expert Chris Dokomajilar ran the numbers for us on a month-to-month basis and found that not only was venture money flowing during the panicky month of March, but it was also hitting home in record sums compared to the last 26 months of deal flow.

Say what?

As you can see in the top chart below, Dokomajilar outlined how the industry racked up $2.41 billion in total for March, just barely ahead of one other topper during the heady days of August 2018.

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FDA Commissioner Stephen Hahn and President Donald Trump at a press briefing on March 19, 2020. (AP Images)

Biotech ex­ecs warn that the FDA is fum­bling their re­sponse to the Covid-19 open-door promise, de­lay­ing progress

A few days ago the FDA touted a procedure for Covid-19 meds that committed the agency to immediate action for developers, formalizing a high-speed response that’s been promised for weeks.

Bioregnum Opinion Column by John Carroll

Decisions that once required months would be measured in hours under the Coronavirus Treatment Acceleration Program. “In many cases” trial protocols could be hammered out in less than a single day. If you had a potential solution to the crisis, the appropriate staffer would be in touch “to get studies underway quickly.”

It would be the ultimate high-speed regulatory pathway from Phase I to approval. Red tape was banished.

But it’s clear that for some — and quite likely many — biopharma execs, the actual agency response has not measured up to the promise. Beyond the front ranks of advanced companies in the field, like Gilead, or for drugs endorsed by President Trump, it may not even come close.

“The first response is this form letter everyone gets,” says one biotech CEO who’s reached out to the FDA on Covid-19. And when you try to cut through that, the ball gets dropped as it is passed from top officials to the frontline staff actually charged with getting things done.

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GSK's Hal Bar­ron buys a $250M stake in George Scan­gos' Vir and makes a bee­line to the clin­ic with Covid-19 an­ti­bod­ies

GlaxoSmithKline is diving straight into the swirling waters of Covid-19 R&D work, and investing $250 million to grab a chunk of equity in one of the emerging stars in infectious disease research to make it official.

GSK put out word this morning that it is partnering with Vir Biotechnology $VIR, the infectious disease startup founded in the Bay Area by former Biogen CEO George Scangos. They’re planning a leap into Phase II studies for 2 preclinical antibody candidates — VIR-7831 and VIR-7832 — that have been engineered to target the SARS-CoV-2 spike protein.

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UP­DAT­ED: A small, ob­scure biotech just won big with their IPO. In this mar­ket. Are you kid­ding me?

How could a small, largely unknown biotech that emerged from stealth mode just months ago with early-stage cancer programs jump onto Wall Street in the middle of a Category 6 financial hurricane and sail through with a $165 million IPO?

And what does that mean for the rest of the industry waiting to see just how much damage global lockdowns will wreak on clinical development?

The biotech is a company called Zentalis. The crew there nabbed an $85 million crossover round late last year — notably waiting 5 years before waving the numbers around to attract attention, according to my read of a FierceBiotech story. Perceptive joined in, but the syndicate was not in general the kind of marquee affair that gets tongues wagging.

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Ready to de­clare a de­fin­i­tive come­back in two months, Im­munomedics stops PhI­II ear­ly, re­cruits new CEO

More than a year ago, hit by a surprise complete response letter from the FDA, Immunomedics bid its then-CEO, Michael Pehl, adieu and began a 15-month quest to resolve the manufacturing issues cited in the CRL and seek a new leader — all the while moving forward with a Phase III study on its lead drug for metastatic triple-negative breast cancer.

Today the biotech said their stars are finally aligning. Not only is Novartis Oncology vet Harout Semerjian coming on board as CEO to steer what they believe will be a smooth sail to a new PDUFA date in June, Immunomedics has also been informed that their late-stage trial can be stopped early due to “compelling evidence of efficacy.”

An­oth­er day, an­oth­er boat­load for biotech. Deer­field adds $840M to rush of ven­ture dol­lars

The biotech dollars just keep rolling in.

Even as the world economy faces an economic contraction unprecedented in nature, biotech venture capital firms are announcing huge new investment pots. The latest? Deerfield Management Co.

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Small mol­e­cules, bi­o­log­ics and now gene ther­a­pies: Ger­many's Evotec adds an­oth­er feath­er to its R&D cap

German drug discovery company Evotec — which has a thriving rolodex of biopharma partners such as Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda — is now venturing into gene therapies.

The company swallowed Seattle-based Just Biotherapeutics, a company focused on reducing the cost of manufacturing protein therapies last year. It is now setting up a dedicated R&D site for gene therapies in Austria, in an effort to achieve a “modality-agnostic” repertoire — small molecules, biologics and now gene therapies.

A pair of PhI­II fail­ures spells last rites for Men­lo’s once-promis­ing Mer­ck drug

Four months after an intercontinental merger, Menlo Therapeutics is counting yet another pair of trial failures — ones with significant consequences for the companies, their shareholders and the drug.

In two pivotal Phase III trials, Menlo’s lead drug serlopitant failed to treat pruritus associated with prurigo nodularis — basically itchiness from a particular skin disease that causes red lesions on a person’s arms or legs. Serlopitant has long been the company’s only drug and as recently as 2018, it looked promising enough to support a stock price of $37. In April of that year, a Phase II failure demolished the stock price overnight: $35 to $9. Other subsequent stumbles trickled the ticker down to just above $2.