#ES­MO17: Eli Lil­ly sets the stage for a CDK 4/6 show­down with Pfiz­er, No­var­tis — but not ex­act­ly to its ad­van­tage

MADRID — Eli Lil­ly came to ES­MO with an eye to dis­tin­guish­ing abe­maci­clib as it pre­pares to launch its CDK 4/6 can­cer drug against ri­vals from No­var­tis and Pfiz­er. It may have done that, but not ex­act­ly as Lil­ly ex­ecs would have liked.

Cur­rent­ly un­der pri­or­i­ty re­view at the FDA, abe­maci­clib reg­is­tered the pos­i­tive da­ta need­ed to win over reg­u­la­tors in MONARCH-3. Re­searchers tracked a 46% re­duc­tion in the risk of dis­ease pro­gres­sion in the tri­al arm in­clud­ing pre­vi­ous­ly un­treat­ed women with ad­vanced breast can­cer, com­par­ing a com­bi­na­tion of abe­maci­clib added to stan­dard care. There was al­so a 59% re­sponse rate on tu­mor shrink­age com­pared to 44% in the con­trol arm pro­vid­ed stan­dard ther­a­py.

The me­di­an pro­gres­sion-free sur­vival rate and over­all sur­vival num­bers aren’t in yet.

That’s all ap­proval-wor­thy da­ta, but not nec­es­sar­i­ly the kind of ear­ly ef­fi­ca­cy re­sults that will in­tim­i­date any­one at Pfiz­er and No­var­tis wor­ried about mar­ket share.

Where it gets trou­ble­some for Eli Lil­ly, though, is on the side ef­fect da­ta.

Rates of di­ar­rhea and neu­trope­nia were 81.3% and 41.3% with abe­maci­clib, and 29.8% and 1.9% with place­bo, re­spec­tive­ly.

David Ricks, Eli Lil­ly CEO

The in­ves­ti­ga­tors are quick to say that the di­ar­rhea is typ­i­cal­ly fair­ly low grade and read­i­ly man­aged, but it’s the kind of com­mon ef­fect that could well per­suade doc­tors to pre­fer ei­ther Kisqali or Ibrance for their HR-pos­i­tive, HER2-neg­a­tive pa­tients.

That’s not the kind of dis­tin­guish­ing fac­tor you want to raise, es­pe­cial­ly when you’re late to the game.

Ever­core ISI’s Umer Raf­fat al­so sent out a note on Sun­day high­light­ing an im­bal­ance of throm­boem­bol­ic events, which could earn a warn­ing la­bel from the FDA that would give com­peti­tors a dis­tinct edge as well.

Not good.

Eli Lil­ly has as­sert­ed that it can make abe­maci­clib the best-in-class pick among the three CDK 4/6 drugs field­ed by three phar­ma gi­ants with se­ri­ous sales ef­forts. And that con­fi­dence has built peak sales es­ti­mates to close to $2 bil­lion a year. For now.

Re­searchers al­so high­light­ed new ev­i­dence that sug­gests there are pa­tient groups that would ben­e­fit more by start­ing on stan­dard ther­a­py and adding a CDK 4/6 drug as a sec­ond-line ther­a­py.

“Now for the first time,we have in­sights sug­gest­ing that pa­tients with cer­tain clin­i­cal char­ac­ter­is­tics may ben­e­fit dif­fer­ent­ly from treat­ment with a CDK 4/6 in­hibitor, in­clud­ing the pos­si­bil­i­ty that some pa­tients with a good prog­no­sis may be able to start on en­docrine ther­a­py alone,” said lead au­thor An­ge­lo Di Leo. “In such pa­tients, CDK 4/6 in­hibitors could po­ten­tial­ly be re­served as a next line of treat­ment for metasta­t­ic dis­ease. This idea war­rants fur­ther study giv­en our da­ta. In our study, near­ly one-third of pa­tients had bone metas­tases on­ly or a tu­mor re­laps­ing sev­er­al years af­ter stop­ping ad­ju­vant en­docrine ther­a­py. This is a clin­i­cal­ly rel­e­vant pro­por­tion of pa­tients for whom we may con­sid­er de­lay­ing use of a CDK 4/6 in­hibitor. This may be a more op­ti­mal treat­ment strat­e­gy for some pa­tients since it can avoid the tox­i­c­i­ty of first line CDK 4/6 in­hibitors and save costs.”

Pay­ers won’t over­look that ob­ser­va­tion.

We won’t have long to wait be­fore things heat up on the mar­ket. Lil­ly nabbed a pri­or­i­ty re­view for this drug in Ju­ly, set­ting up a fi­nal de­ci­sion by Jan­u­ary.

Lil­ly needs a steady stream of sig­nif­i­cant new drug ap­provals if new CEO Dave Ricks ex­pects to keep its in­vestors hap­py. The FDA have helped out by putting baric­i­tinib back on track, but we won’t know that for sure un­til next year.

Im­age cred­it: ES­MO

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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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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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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Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

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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.

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.