Eli Lil­ly con­ducts an au­top­sy of an Alzheimer’s megaflop

For four years Eli Lil­ly $LLY com­mit­ted one of the biggest clin­i­cal ef­forts in the com­pa­ny’s his­to­ry to prov­ing that it could get solanezum­ab right on Alzheimer’s. Hav­ing nav­i­gat­ed through mul­ti­ple tri­al fail­ures al­ready, in­ves­ti­ga­tors were con­vinced that if they took what they had learned, changed the pa­tient pop­u­la­tion, stick­ing to on­ly pa­tients with a mild form of the dis­ease while us­ing bet­ter di­ag­nos­tics — even chang­ing the end­points in the lead up to the fi­nal read out — they could make a case that this drug could make a sig­nif­i­cant im­prove­ment for pa­tients.

In­stead, they came up with a set of mod­est fig­ures in­di­cat­ing that at best they had mere­ly tapped the brakes on the dis­ease. And to­day they spelled it all out in what will like­ly be the post mortem on what once fac­tored in as one of the biggest clin­i­cal gam­bles in the his­to­ry of bio­phar­ma.

Solanezum­ab was de­signed to flush amy­loid be­ta, a tox­ic pro­tein which of­ten clus­ters in the brains of Alzheimer’s vic­tims. The in­ves­ti­ga­tors of­fered some mixed mes­sages on just how ef­fec­tive so­la was in re­duc­ing a-be­ta de­posits. In­ves­ti­ga­tor tracked sig­nif­i­cant changes in plas­ma lev­els of the pro­tein, but check­ing amy­loid de­posits with PET imag­ing pro­duced no sig­nif­i­cant changes. Re­searchers in oth­er pro­grams will be fol­low­ing that close­ly as they make their own as­saults on amy­loid, which re­mains a key fo­cus. There is a grow­ing con­sen­sus in the field, though, that it will take com­bi­na­tion ther­a­pies to have a re­al im­pact on the mem­o­ry-wast­ing dis­ease that af­flicts mil­lions.

Look­ing for a dom­i­nant new block­buster, they had to set­tle for en­cour­ag­ing pa­tients to hope for some­thing bet­ter.

Lawrence S. Honig, MD, PhD, Co­lum­bia

“Alzheimer’s is a chal­leng­ing dis­ease that re­searchers have been com­mit­ted to study­ing for some years,” said Lawrence S. Honig, MD, PhD, pro­fes­sor of neu­rol­o­gy at Co­lum­bia Uni­ver­si­ty Med­ical Cen­ter and prin­ci­pal in­ves­ti­ga­tor of the EX­PE­DI­TION3 study, pre­sent­ed the da­ta at the meet­ing. “Now is not the time to give up. While the out­come of this study is not what we had hoped for, it is rea­son­able to be­lieve that dis­ease mod­i­fy­ing ther­a­pies to slow down the pro­gres­sion of Alzheimer’s dis­ease will be dis­cov­ered.”

The key fail­ure point was on ADAS-Cog14, which mea­sures a per­son’s cog­ni­tive func­tions, in­clud­ing mem­o­ry, at­ten­tion and lan­guage abil­i­ties. In­ves­ti­ga­tors tracked an 11% re­duc­tion in the rate of de­cline, a clear miss with a p-val­ue of .095.

The sec­ondary end­points weren’t that much dif­fer­ent.

  • There was the Mi­ni-Men­tal State Ex­am­i­na­tion, or MMSE, with a 13% slow­ing in cog­ni­tive de­cline.
  • The Clin­i­cal De­men­tia Rat­ing-Sum of Box­es (CDR-SB) scale showed a 15 per­cent slow­ing in de­cline (p=0.004) be­tween pa­tients treat­ed with solanezum­ab and pa­tients treat­ed with place­bo.
  • There was a 14 per­cent slow­ing of de­cline (p=.019) as mea­sured by the Alzheimer’s Dis­ease Co­op­er­a­tive Study- In­stru­men­tal Ac­tiv­i­ties of Dai­ly Liv­ing (AD­CS-iADL). The AD­CS-iADL scale mea­sures a per­son’s in­de­pen­dent per­for­mance in com­plex ac­tiv­i­ties of dai­ly liv­ing such as par­tic­i­pat­ing in a con­ver­sa­tion, prepar­ing a meal or shop­ping.
  • The Func­tion­al Ac­tiv­i­ties Ques­tion­naire did not show a sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence be­tween pa­tients treat­ed with solanezum­ab and pa­tients treat­ed with place­bo (7 per­cent re­duc­tion in de­cline, p=0.140). The FAQ scale is a dif­fer­ent in­for­mant-based mea­sure of func­tion­al abil­i­ties. In­for­mants pro­vide per­for­mance rat­ings of the pa­tient on ten com­plex high­er-or­der ac­tiv­i­ties.

There was, though, a greater chance that the drug arm would suf­fer from spinal os­teoarthri­tis: 1.1 per­cent in the solanezum­ab group, 0.4 per­cent in the place­bo group. And there was a 0.9 per­cent rate of dy­suria in the solanezum­ab group.

In the mean­time, you can rack up an­oth­er set­back in a field that has known on­ly late-stage fail­ure in the past decade.

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
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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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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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.

Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cellarity started with a simple — but far from easy — idea that Avak Kahvejian and his team were floating around at Flagship Pioneering: to digitally encode a cell.

As he and his senior associate Nick Plugis dug deeper into the concept, they found that most of the models others have developed take a bottom-up approach, where they assemble the molecules inside cells and the connections between them from scratch. What if they opt for a top-down approach, aided by single-cell transcriptomics and machine learning, to gauge the behavior of the entire cellular network?

As­traZeneca teams up with Deep Mat­ter for AI drug de­vel­op­ment; Can­cer biotech Im­munOs rais­es $15M

→ AstraZeneca is aligning itself with the big data company DeepMatter, which is focused on attaining reproducibility in chemistry. The latter is set to help the British drugmaker improve its compound synthesis productivity by using an AI-powered platform to capture real-time data to track factors such as temperature, pressure, ultraviolet light levels and other factors in combination with data on solvents, catalysts, and reagents. “By capturing in-situ chemical data alongside the experimental intent, observations and outcomes, it is expected that machine learning and AI algorithms could yield cost and time savings whilst also providing novel insights into chemistry,” the companies said on Monday.