Al­ny­lam achieves break­through RNAi suc­cess as PhI­II patisir­an study hits all goals, shares soar

Al­ny­lam in­vestors $AL­NY can now start breath­ing again.

The big Cam­bridge, MA-based biotech says that their Phase III study of patisir­an — part­nered with Sanofi — scored a pos­i­tive hit for the pri­ma­ry as well as all sec­ondary end­points in treat­ing rare cas­es of hered­i­tary AT­TR amy­loi­do­sis with polyneu­ropa­thy.


The score sets up Al­ny­lam’s first new drug ap­pli­ca­tion with the FDA be­fore the end of this year with a Eu­ro­pean fil­ing fol­low­ing soon af­ter, while Sanofi gears up for a slate of ap­pli­ca­tions around the globe.

Shares of Al­ny­lam shot up more than 20% in pre-mar­ket trad­ing Wednes­day, as the com­pa­ny added to a mar­ket cap that start­ed to­day at just un­der $7 bil­lion. But it didn’t stop there, with shares up 32% in ear­ly trad­ing as ex­cite­ment about the news spread fast. By mid-af­ter­noon, the stock was up 49%, worth more than $3 bil­lion in mar­ket cap.

Al­ny­lam’s gung-ho CEO John Maraganore, who has steered the com­pa­ny through calm seas and mael­stroms for more than a decade as he pi­o­neered one of the biggest RNA ven­tures in the in­dus­try, was clear­ly beam­ing as the in­dus­try ea­ger­ly pounced on the news of the first pos­i­tive Phase III study for an RNAi drug. He said:

This mo­ment is the cul­mi­na­tion of a 15-year jour­ney of tire­less work by count­less con­trib­u­tors who have over­come enor­mous sci­en­tif­ic and busi­ness chal­lenges to make RNAi ther­a­peu­tics a re­al­i­ty.

Sanofi, which bet big on Al­ny­lam when it in­vest­ed $700 mil­lion in­to the com­pa­ny more than three years ago, al­so cheered the re­sults.

The suc­cess for patisir­an comes af­ter some big clin­i­cal set­backs for Al­ny­lam, which has been dogged for years over the safe­ty is­sues raised by RNAi ther­a­pies. About 8 years ago big phar­ma large­ly bailed on RNAi, dis­turbed by the de­vel­op­ment chal­lenges and the time it would take to de­liv­er ma­jor new ther­a­pies. But Maraganore nev­er flinched, in­sist­ing through­out that his com­pa­ny could de­liv­er on its pipeline promis­es.

All we know right now is what the top line re­sults are.

The pri­ma­ry end­point for the study was the change from base­line in the mod­i­fied neu­ropa­thy im­pair­ment score, where re­searchers reg­is­tered a sta­tis­ti­cal­ly sig­nif­i­cant re­sult. Pa­tients on patisir­an al­so scored an im­prove­ment in their qual­i­ty of life. And there were hits on all 5 sec­on­daries:

NIS-W, the sub­do­main of mNIS+7 as­sess­ing mus­cle strength;

Rasch-built Over­all Dis­abil­i­ty Scale (R-ODS), a pa­tient re­port­ed out­come mea­sure of dai­ly liv­ing and dis­abil­i­ty;

10-me­ter walk test, as­sess­ing gait speed;

Mod­i­fied body mass in­dex (mB­MI), as­sess­ing nu­tri­tion­al sta­tus; and

COM­PASS-31, a ques­tion­naire to as­sess au­to­nom­ic symp­toms.

In ad­di­tion, while de­tails are lack­ing, the safe­ty pro­file looked good. Pa­tients in both groups ex­pe­ri­enced ad­verse events, but the drug arm com­pared fa­vor­ably with what we know about the place­bo group. Paul Mat­teis at Leerink not­ed:

In the wake of the re­cent fi­tusir­an set­back – and al­so the dis­con­tin­u­a­tion of re­vusir­an last fall – the pos­i­tive patisir­an re­sult with seem­ing­ly clean safe­ty is like­ly to im­prove sen­ti­ment sig­nif­i­cant­ly. Specif­i­cal­ly, the mor­tal­i­ty rate in the patisir­an arm (4.7%) was low­er than that seen on place­bo (7.8%); giv­en the small N it’s de­bat­able whether or not this con­sti­tutes a true im­prove­ment, but in any case it’s very en­cour­ag­ing with re­spect to RNAi safe­ty. Iron­i­cal­ly, more re­cent set­backs for AL­NY (re­vusir­an and then fi­tusir­an) have come from next-gen RNAi com­pounds that do not uti­lize the old­er, lipid­nanopar­ti­cle tech­nol­o­gy, which is the case for patisir­an. But even de­spite this dif­fer­ence, we ex­pect the re­sult this morn­ing to read pos­i­tive­ly on the plat­form and tech­nol­o­gy over­all.

But it won’t help Io­n­is, which has a com­pet­ing ther­a­py. That drug is now be­ing con­sid­ered an al­so ran against Al­ny­lam’s ther­a­py, with some an­a­lysts ex­pect­ing patisir­an to claim an 80% mar­ket share. Io­n­is stock $IONS plunged 10% this morn­ing.

Maraganore, this year’s BIO chair­man, is one of the most fa­mil­iar fig­ures in the biotech world. And he had plen­ty of sup­port to­day from the cheer­ing sec­tion on Twit­ter.

“This is a sig­nif­i­cant mile­stone that sup­ports our be­lief that RNAi ther­a­peu­tics have the po­ten­tial to be­come an in­no­v­a­tive new class of med­i­cines for pa­tients with rare ge­net­ic dis­eases,” said Elias Zer­houni, the pres­i­dent of R&D at Sanofi. “The APOL­LO da­ta sug­gest that patisir­an could help im­prove the lives of peo­ple liv­ing with hAT­TR amy­loi­do­sis with polyneu­ropa­thy, a pa­tient pop­u­la­tion in ur­gent need of ad­di­tion­al treat­ment op­tions. We look for­ward to work­ing with Al­ny­lam to make patisir­an avail­able around the globe as quick­ly as pos­si­ble.”

 

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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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

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.

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?

Sanofi’s big week in­cludes a promis­ing PhI­II for an or­phan dis­ease drug, with plans for a pitch to the FDA

The biopharma R&D food chain is paying off with a plan at Sanofi to pitch regulators on a new drug for an orphan disease called cold agglutinin disease.

The pharma giant ushered out a statement Tuesday morning — after it spelled out plans to radically restructure the company, abandoning cardio and diabetes research altogether — saying that their C1s inhibitor sutimlimab had cleared the pivotal study.