Out to shake up PC­SK9 mar­ket, Med­i­cines Co boasts of piv­otal PhI­II win for in­clisir­an

The Med­i­cines Com­pa­ny’s first piv­otal Phase III re­sults for in­clisir­an are in, and the biotech can’t wait to high­light the cho­les­terol-low­er­ing po­ten­tial of its long-act­ing drug.

Mark Tim­ney

Ahead of a da­ta pre­sen­ta­tion of ORI­ON-11 at next week’s Eu­ro­pean So­ci­ety of Car­di­ol­o­gy, The Med­i­cines Com­pa­ny is putting out word that in­clisir­an — an RNAi ther­a­peu­tic li­censed from Al­ny­lam that works by pre­vent­ing PC­SK9 from be­ing syn­the­sized in the liv­er — met all pri­ma­ry and sec­ondary end­points. The ef­fi­ca­cy was “con­sis­tent with find­ings from Phase 1 and 2 stud­ies” and the safe­ty pro­file was “at least as fa­vor­able” as in pre­vi­ous Phase II stud­ies.

Baird’s Mad­hu Ku­mar added that in speak­ing with man­age­ment, the re­sults were “con­sis­tent with mod­el­ing work pre­vi­ous­ly de­scribed to rep­re­sent a 50%-55% re­duc­tion in LDL-C” — though he em­pha­sized da­ta at the ESC will be need­ed to con­firm a win here.

Mean­while, Umer Raf­fat of Ever­core ISI ze­roed in on the claim about a clean safe­ty pro­file, which was “by and far the biggest is­sue” head­ing in­to Phase III, call­ing the topline re­sults pos­si­bly “the sin­gle most im­por­tant piece of val­i­da­tion for RNAi safe­ty.”

Shares $MD­CO rose 12.79% to $38.03 pre-mar­ket.

Pa­tients who have com­plet­ed ORI­ON-11 will now join co­horts from ORI­ON-9 and -10 for ORI­ON-8, an open-la­bel ex­ten­sion study to eval­u­ate the dos­ing of in­clisir­an over three years.

ORI­ON-11 and -10 both en­rolled pa­tients with ath­er­o­scle­rot­ic car­dio­vas­cu­lar dis­ease and el­e­vat­ed LDL cho­les­terol de­spite statin ther­a­py; the for­mer was con­duct­ed in sev­en coun­tries ex-US while the lat­ter took place in the US. The re­sults for ORI­ON-10 as well as -9 — which tar­get pa­tients with het­erozy­gous fa­mil­ial hy­per­c­ho­les­terolemia — are ex­pect­ed lat­er this quar­ter.

That bulky da­ta pack­age — with each tri­al in­volv­ing more than a thou­sand pa­tients — will be sent to the FDA by the end of this year and to the EMA in Q1 2020.

The da­ta pre­sen­ta­tion at ESC can al­so bode well for Al­ny­lam $AL­NY, Mani Foroohar of SVB Leerink not­ed, es­pe­cial­ly with re­gards to ap­ply­ing its GalNAc-con­ju­gat­ed RNAi plat­form in large pop­u­la­tion, pri­ma­ry care in­di­ca­tions.

While mon­o­clon­al an­ti­bod­ies from Re­gen­eron/Sanofi and Am­gen have beat in­clisir­an to the mar­ket, Baird an­a­lysts have pre­dict­ed the drug will be “as­cend­ing the Iron Throne of PC­SK9 drugs” due most­ly to its dos­ing sched­ule. Un­like Pralu­ent and Repatha, which are ad­min­is­tered month­ly or twice-month­ly, in­clisir­an can be giv­en just twice a year af­ter an ini­tial in­ter­val of three months.

“We be­lieve this dos­ing sched­ule is at­trac­tive to pa­tients and can im­prove ad­her­ence, since cur­rent­ly on­ly 55-60% pa­tients are com­pli­ant on PC­SK9 Ab ther­a­py,” Jef­feries an­a­lysts have not­ed.

No­tably, ORI­ON-11 ex­clud­ed pa­tients with ac­tive liv­er dis­ease, which the com­pa­ny said is “not un­com­mon for stud­ies of dys­lipi­demia med­ica­tions.” While a case of liv­er en­zyme el­e­va­tion cropped up in Phase II, it was deemed un­re­lat­ed to the drug. Re­cent stud­ies com­pris­ing re­nal­ly im­paired pa­tients al­so sug­gest­ed in­clisir­an is safe for that group, and that they do not re­quire dose ad­just­ment.

“This is a mo­men­tous oc­ca­sion that fur­ther re­in­forces our con­fi­dence in the tremen­dous po­ten­tial of in­clisir­an to fun­da­men­tal­ly change the treat­ment of car­dio­vas­cu­lar dis­ease,” said CEO Mark Tim­ney, who suc­ceed­ed long­time chief Clive Mean­well in De­cem­ber 2018.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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