Analy­sis shows The Med­i­cines Com­pa­ny/Al­ny­lam drug in­clisir­an safe for re­nal­ly-im­paired pa­tients

About a week af­ter long-term Phase II da­ta on The Med­i­cines Com­pa­ny’s $MD­CO Al­ny­lam $AL­NY-part­nered twice-year­ly cho­les­terol fight­er, in­clisir­an, was in­di­cat­ed as safe and ef­fec­tive as the ap­proved once-month­ly Repatha and Pralu­ent, its man­u­fac­tur­ers pre­sent­ed da­ta at the Eu­ro­pean Ath­er­o­scle­ro­sis So­ci­ety Con­gress from two tri­als in­volv­ing re­nal­ly-im­paired pa­tients.

Al­to­geth­er da­ta from 279 pa­tients across the two tri­als showed that pa­tients with dif­fer­ent lev­els of re­nal func­tion achieved con­sis­tent re­duc­tions in low-den­si­ty lipopro­tein cho­les­terol (LDL-C), or “bad” cho­les­terol with in­clisir­an treat­ment, and did not re­quire dose ad­just­ment, The Med­i­cines Co said over the week­end.

Re­nal im­pair­ment has been shown to fre­quent­ly ac­com­pa­ny and in­crease the risk of ath­er­o­scle­rot­ic car­dio­vas­cu­lar dis­ease (AS­CVD) — but da­ta from the Phase II ORI­ON-1 tri­al and Phase I ORI­ON-7 tri­al did not raise any safe­ty con­cerns as­so­ci­at­ed with in­clisir­an, an­a­lysts said.

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 $PFE 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 in­sur­er push­back 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 — as well as safe use in re­nal­ly-im­paired pa­tients, and their man­u­fac­tur­ers have al­so their prices 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.

While re­nal im­pair­ment did af­fect in­clisir­an’s phar­ma­co­ki­net­ic (PK) pro­file, with longer drug ex­po­sure and slow­er drug clear­ance in se­vere­ly re­nal­ly-im­paired sub­jects, changes in in­clisir­an PK had ef­fec­tive­ly no im­pact on the drug’s phar­ma­co­dy­nam­ic (PD) pro­file, Baird an­a­lysts un­der­scored.

Piv­otal late-stage da­ta on in­clisir­an are ex­pect­ed in the third quar­ter, and the com­pa­ny ex­pects to sub­mit reg­u­la­to­ry ap­pli­ca­tions in the Unit­ed States and Eu­rope soon af­ter.

“PC­SK9 in­hibitors Pralu­ent and Repatha have shown to be ef­fec­tive in low­er­ing LDL-C in pa­tients with re­nal im­pair­ment. With the ORI­ON-7 re­sults in­clisir­an joins the ranks of oth­er PC­SK9 in­hibitors in demon­strat­ing ef­fi­ca­cy and safe­ty in this im­por­tant sub­set of AS­CVD pa­tients. In ad­di­tion, the pos­i­tive ORI­ON-7 re­sults pro­vide the ra­tio­nal for the in­clu­sion of pa­tients with se­vere re­nal im­pair­ment in the on­go­ing ORI­ON Ph.3 tri­als,” SVB Leerink an­a­lysts wrote in a note.

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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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.

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.

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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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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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

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.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

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.