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.

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.