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.

Biotech in­vestors and CEOs see two paths to growth, but are they equal­ly vi­able?

The dynamic in the biotech market has been highly volatile in the last few years, from the high peaks immediately after the COVID vaccine in 2021, to the lowest downturns of the last 20 years in 2022. This uncertainty makes calling the exact timing of the market’s turn something of a fool’s errand, according to Dr. Chen Yu, Founder and Managing Partner of TCG Crossover (TCG X). He speaks with RBC’s Noël Brown, Head of US Biotechnology Investment Banking, about the market’s road ahead and two possible paths for growth.

Casey McPherson shows his daughters Rose (left) and Weston around Everlum Bio, a lab that he co-founded to spark a treatment for Rose and others with ultra-rare conditions. (Ilana Panich-Linsman)

Fa­ther starts lab af­ter in­tel­lec­tu­al prop­er­ty is­sues stymie rare dis­ease drug de­vel­op­ment

Under bright lab lights, Casey McPherson holds his 6-year-old daughter, Rose. His free hand directs Rose’s gaze toward a computer screen with potential clues in treating her one-of-a kind genetic condition.

Gray specks on the screen show her cells that scientists reprogrammed with the goal of zeroing in on a custom medicine. McPherson co-founded the lab, Everlum Bio, to spark a treatment for Rose — and others like her. A regarded singer-songwriter, McPherson never imagined going into drug development.

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Fireside chat between Hal Barron and John Carroll, UKBIO19

It’s time we talked about bio­phar­ma — live in Lon­don next week

Zoom can only go so far. And I think at this stage, we’ve all tested the limits of staying in touch — virtually. So I’m particularly happy now that we’ve revved up the travel machine to point myself to London for the first time in several years.

Whatever events we have lined up, we’ve always built in plenty of opportunities for all of us to get together and talk. For London, live, I plan to be right out front, meeting with and chatting with the small crowd of biopharma people we are hosting on October 12 at Silicon Valley Bank’s London headquarters. And there’s a lengthy mixer at the end I’m most looking forward to, with several networking openings between sessions.

Take­da to pull key hy­poparathy­roidism drug from the mar­ket af­ter years of man­u­fac­tur­ing woes

Takeda on Tuesday morning made an announcement that almost 3,000 people with the rare disease known as hypoparathyroidism were fearing.

Due to unresolved supply issues and manufacturing woes, Takeda said it will cut its losses and discontinue its hypoparathyroidism drug, known as Natpara (parathyroid hormone), halting all manufacturing of the drug by the end of 2024, but the entire inventory will be available until depleted or expired, a company spokesperson said via email.

Pfizer and BioNTech's original Marvel comic book links evolving Covid vaccine science to Avengers' evolving villain-fighting tools.(Source: Pfizer LinkedIn post)

Pfiz­er, BioN­Tech part­ner with Mar­vel for Avengers and Covid-fight­ing com­ic book

Pfizer and BioNTech are collaborating with Marvel to celebrate “everyday” people getting Covid-19 vaccines in a custom comic book.

In the “Everyday Heroes” digital comic book, an evolving Ultron, one of the Avengers’ leading villains, is defeated by Captain America, Ironman and others. The plotline and history of Ultron is explained by a grandfather who is waiting with his family at a clinic for Covid-19 vaccinations.

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Kaile Zagger, Infinant Health CEO

UC Davis mi­cro­bio­me spin­out re­brands in­fant sup­ple­ment busi­ness with na­ture fo­cus

When Kaile Zagger took the helm of UC Davis spinout Evolve Biosystems several months ago, the company billed itself as a probiotic maker.

However, she believes the company’s Evivo supplement designed to help infants develop a healthy gut microbiome is “so much more” — and that, she said, calls for a rebrand.

Evolve has, well, evolved into Infinant Health, the company announced on Monday. The new name is a mash-up of the words “infant” and “infinite,” representing the company’s goal of expanding beyond infant care. While its sole product, Evivo, is intended for newborns, Infinant is “quickly developing” an option for kids through the age of two.

FDA+ roundup: Ad­comm date set for Cy­to­ki­net­ics heart drug; New gener­ic drug guid­ance to re­duce fa­cil­i­ty de­lays

The FDA has set Dec. 13 as the day that its Cardiovascular and Renal Drugs Advisory Committee will review Cytokinetics’ potential heart drug, setting up a key vote ahead of a Feb. 28, 2023 PDUFA date.

The drug, known as omecamtiv mecarbil, read out its first Phase III in November 2020, hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as the key to breaking into the market, failing to significantly differ in reducing cardiovascular death from placebo.

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Bob Azelby, Eliem Therapeutics CEO

Eliem says ear­li­er drug ex­po­sure is­sues have been re­solved, drops one epilep­sy in­di­ca­tion

After being forced to delay two Phase IIa trials and blaming CMC issues on a Phase Ib miss, Eliem Therapeutics believes it’s now in the clear.

The Seattle and UK-based biotech put out word Wednesday morning about how it conducted new early-stage studies to confirm why low exposure issues arose during the Phase Ib. After researchers compared the results of the studies, Eliem found “no meaningful difference” between them and ruled out CMC as the reason for the foiled Phase Ib study, the company said in a press release.

GSK touts topline win for PD-1 in head-to-head with Keytru­da — while steer­ing next big check­point drug in­to PhI­II

GSK is claiming a win for what it calls the largest head-to-head trial pitting a PD-1 against Merck’s best-selling Keytruda in a type of lung cancer, as its Jemperli met the primary endpoint of objective response rate.

In a separate positive move, GSK says it’s moving both arms of the COSTAR Lung trial into Phase III to test Jemperli as well as the TIM-3 inhibitor cobolimab.

Hesham Abdullah, GSK’s global head of oncology development, said in a statement that the two trials “support the ambition for dostarlimab to become the backbone of our ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options.”

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