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.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.


ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology


ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development


CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

UP­DAT­ED: As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Ted Ashburn. Oncorus

Cowen, Per­cep­tive lead $79.5M Se­ries B for 's­tand­out' biotech shep­herd­ing on­colyt­ic virus to clin­ic

As several Big Pharma players secure biotech partners in the oncolytic virus space for new immuno-oncology combos, Cowen and Perceptive Advisors have come out with their own bet on a startup that promises to shine.

The marquee investors are joining MPM, Deerfield, Celgene, Astellas, Arkin and UBS in backing the drug developer, Oncorus, which will now deploy the $79.5 million in Series B cash toward clinical development of its lead program. Other new investors include Surveyor Capital, Sphera Funds, IMM Investment, QUAD Investment Management, UTC Investment, SV Investment Corp and Shinhan Investment-Private Equity, the last five of which are Korean-based funds.

Fu­til­i­ty analy­sis au­gurs de­feat in piv­otal tri­al test­ing of Nu­Cana's lead drug in metasta­t­ic pan­cre­at­ic can­cer

Nearly two years after making its public debut, UK-based NuCana’s mission to make chemotherapies more potent and safer was dealt a blow, after a pivotal study testing its lead experimental drug halted enrollment in a hard-to-treat advanced form of cancer, following a futility analysis.

The drug, Acelarin, is being evaluated for use in metastatic pancreatic cancer patients who were not considered suitable for combination chemotherapy. In the late-stage ACELARATE study — which compared the experimental drug against the chemotherapy gemcitabine — 200 patients had been enrolled by the sponsor, Clatterbridge Cancer Centre, before an analysis from an independent safety and data monitoring panel suggested the study’s main goal would not be met.

UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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