Long-term in­clisir­an da­ta sug­gest The Med­i­cines Com­pa­ny/Al­ny­lam drug will flour­ish in piv­otal study, dis­rupt 'bad' cho­les­terol mar­ket

Ahead of the keen­ly an­tic­i­pat­ed piv­otal late-stage read­out for its Al­ny­lam $AL­NY-part­nered long-act­ing cho­les­terol fight­er in­clisir­an, The Med­i­cines Com­pa­ny on Sat­ur­day af­ter­noon un­veiled long-term Phase II da­ta that sug­gest­ed the bian­nu­al-dosed drug is as safe and ef­fec­tive as the ap­proved once-month­ly Repatha and Pralu­ent.

Un­like Repatha from Am­gen $AMGN, as well as Pralu­ent from Re­gen­eron $REGN and Sanofi $SNY — which work by in­hibit­ing the PC­SK9 pro­tein and there­by di­min­ish­ing LDL-C or “bad” cho­les­terol — in­clisir­an is a siR­NA ther­a­py de­signed to curb the pro­duc­tion of the PC­SK9 pro­tein at its source in the liv­er to oust LDL-C from the blood­stream.

De­spite the wide adop­tion of statins, such as Pfiz­er’s near­ly $13 bil­lion-at-peak Lip­i­tor, hy­per­c­ho­les­terolemia and as­so­ci­at­ed car­dio­vas­cu­lar dis­ease is en­dem­ic in the Unit­ed States, rep­re­sent­ing fer­tile ground for fresh, po­tent ther­a­pies to reap lu­cra­tive re­turns. Repatha and Pralu­ent were first ap­proved in 2015 in post-statin pa­tients amidst much fan­fare, but in­stead faced push­back from in­sur­ers for their high stick­er prices ($14,000) that led to low­er-than-ex­pect­ed adop­tion. How­ev­er, since then, tri­als have demon­strat­ed the PC­SK9 in­hibitors al­so sig­nif­i­cant­ly cut car­dio­vas­cu­lar risk — da­ta that are now re­flect­ed on their la­bels — and their man­u­fac­tur­ers have al­so slashed the prices of their re­spec­tive drugs by 60%, in a bid to boost tepid sales. So there is “nowhere for in­clisir­an to hide on ei­ther ef­fi­ca­cy or safe­ty (es­pe­cial­ly safe­ty),” Baird an­a­lysts wrote in a March ini­ti­a­tion note.

Da­ta on Sat­ur­day came from ORI­ON-3 — a fol­low-on tri­al from the Phase II ORI­ON-1 study. Pa­tients who com­plet­ed ORI­ON-1 were en­rolled in ORI­ON-3, and were di­vid­ed in­to two groups. In the first group, sub­jects (n=290) pre­vi­ous­ly treat­ed with any in­clisir­an dose in ORI­ON-1 re­ceived twice-a-year in­jec­tions of in­clisir­an sodi­um 300 mg. The main goal was the mean per­cent change in LDL-C from the ORI­ON-1 base­line val­ue, mea­sured at day 210.

An­a­lysts sug­gest­ed the da­ta bode well for the in­com­ing late-stage in­clisir­an read­out, ex­pect­ed in the third quar­ter. “These re­sults have in­creased our con­vic­tion in in­clisir­an as­cend­ing the Iron Throne of PC­SK9 drugs,” Baird an­a­lysts wrote in a note on Sun­day. The Med­i­cines Com­pa­ny’s shares were up near­ly 9% at $35.95 be­fore the bell on Mon­day.

In the ORI­ON stud­ies, pa­tients with ac­tive liv­er dis­ease were ex­clud­ed, which should al­low “in­clisir­an to avoid most of the ad­verse events seen pre­vi­ous­ly with some GalNAc siR­NA drug can­di­dates,” SVB Leerink an­a­lysts wrote in a note ear­li­er this month. That pre­dic­tion proved per­ti­nent. In terms of safe­ty, in­clisir­an was well tol­er­at­ed and no ma­te­r­i­al safe­ty is­sues were ob­served, The Med­i­cines Com­pa­ny $MD­CO said on Sat­ur­day.

How­ev­er, there was a sin­gle pa­tient with liv­er en­zyme el­e­va­tion, and one pa­tient death due to a stroke, which was deemed un­re­lat­ed to the drug.

“While MD­CO bears will cling to the sin­gle liv­er en­zyme el­e­va­tion event ob­served in ORI­ON-3, sev­er­al con­sid­er­a­tions make that ar­gu­ment un­ten­able,” ar­gued Baird an­a­lysts. For in­stance, the pa­tient that ex­pe­ri­enced the liv­er en­zyme el­e­va­tion was be­ing treat­ed with Arthrotec for a gout flare-up, they wrote. “In­vok­ing Oc­cam’s Ra­zor, the sim­plest ex­pla­na­tion for the liv­er en­zyme el­e­va­tion was the drug known for decades to cause liv­er en­zyme el­e­va­tions.”

Jef­feries an­a­lysts sug­gest­ed that over­all, the da­ta rep­re­sent­ed a “clean safe­ty pro­file…out to 3 years which was one of the key in­vestor ques­tions head­ing in­to the PI­II read­out.”

Da­ta al­so showed that in­clisir­an-treat­ed pa­tients ex­pe­ri­enced a 51% re­duc­tion in LDL-C lev­els through day 210, and time-av­er­aged ab­solute re­duc­tions of 59.4mg/dL for up to 3 years.

Am­gen’s Repatha re­port­ed LDL-C re­duc­tion of 56% at year 3, “in pa­tients with el­e­vat­ed LDL af­ter statin in­tol­er­ance or max-tol­er­at­ed statins (so a slight­ly dif­fer­ent group of pa­tients than ORI­ON-3),” Jef­feries an­a­lysts wrote in a note. “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.”

Apart from Pralu­ent and Repatha, in­clisir­an will like­ly al­so have to con­tend with Es­pe­ri­on’s $ES­PR LDL drug be­mpe­doic acid — which is un­der FDA re­view — al­though it has not shown to be as ef­fec­tive as the ap­proved PC­SK9 drugs.

Mean­while, pa­tients from ORI­ON-3’s group 2 (n=92) were pa­tients giv­en place­bo in ORI­ON-1. They have re­ceived one year of treat­ment with Repatha (140 mg in­jec­tions every two weeks) fol­lowed by three years of treat­ment with in­clisir­an sodi­um 300 mg giv­en on day 360 and 450 and every six months there­after. Da­ta on these pa­tients are ex­pect­ed some­time in 2022.


Im­age source: Shut­ter­stock

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

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.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

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.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

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.

Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.