New analy­sis shows in­clisir­an con­sis­ten­cy in LDL-C re­duc­tion as No­var­tis read­ies for FDA de­ci­sion

As the FDA con­tin­ues its re­view of the for­mer-The Med­i­cines Com­pa­ny, now-No­var­tis can­di­date in­clisir­an ahead of an ex­pect­ed PDU­FA be­fore the year is out, the Swiss phar­ma re­leased pooled da­ta that it hopes bol­sters the case for ap­proval.

A post-hoc analy­sis of two Phase III in­clisir­an tri­als showed con­sis­ten­cy in ef­fi­ca­cy and safe­ty among pa­tients with both hy­per­lipi­demia and ath­er­o­scle­rot­ic car­dio­vas­cu­lar dis­ease de­spite statin ther­a­py, with 99% of pa­tients show­ing greater than 30% place­bo-ad­just­ed re­duc­tion in LDL-C lev­els. The av­er­age re­duc­tion was 54.1% from base­line in the 2,300 in­di­vid­u­als be­tween the two stud­ies.

The analy­sis mea­sured the can­di­date’s pro­file af­ter 17 months of the first dose. Around 88% of pa­tients hit 50% re­duc­tion of LDL-C in at least one point dur­ing the study, and af­ter the 17-month pe­ri­od, al­most two-thirds of pa­tients (66.4%) had a 50% re­duc­tion com­pared to 2.5% per­cent in the place­bo group.

Da­ta for the study were tak­en from the ORI­ON-10 tri­al, look­ing at hy­per­lipi­demia, and the ORI­ON-11 tri­al, ex­am­in­ing AS­CVD. In­clisir­an hit pri­ma­ry end­points of 52% and 50% LDL-C re­duc­tion, re­spec­tive­ly, at 17 months.

In­clisir­an works dif­fer­ent­ly than the big-name LDL-C drugs on the mar­ket, such as Am­gen’s Repatha and Sanofi/Re­gen­eron’s Pralu­ent. While those are mon­o­clon­al an­ti­bod­ies that in­hib­it the PC­SK9 pro­tein, in­clisir­an is a small in­ter­fer­ing RNA that works to pre­vent PC­SK9 from be­ing syn­the­sized in the liv­er.

Though those drugs have set the mar­ket pace since their ap­provals in 2015 with their ef­fi­ca­cy lev­els, they dis­ap­point­ed out of the gate thanks to stick­er shock at the ini­tial prices of around $14,000. The drug­mak­ers have since cut prices by about 60% though, mak­ing it tough for in­clisir­an to el­bow its way in­to the com­pet­i­tive field.

No­var­tis is bank­ing on added con­ve­nience, how­ev­er, as a way to mar­ket in­clisir­an should it re­ceive FDA ap­proval as doc­tors on­ly need to ad­min­is­ter the com­pound twice a year, fol­low­ing an ini­tial dose and a sec­ond dose three months lat­er. Repatha and Pralu­ent re­quire dos­ing ei­ther every two weeks or once a month.

In­clisir­an was large­ly seen as the big prize for No­var­tis when it ac­quired The Med­i­cines Com­pa­ny for $9.7 bil­lion last No­vem­ber. Though No­var­tis ad­mit­ted in doc­u­ments that the biotech like­ly wasn’t worth the $90 per share it was of­fer­ing, the phar­ma de­cid­ed to hon­or the ini­tial price hop­ing to cash in on the drug.

The FDA is ex­pect­ed to reach a de­ci­sion on in­clisir­an be­fore the end of 2020 in the treat­ment for hy­per­lipi­demia among adults who are on a max­i­mal­ly tol­er­at­ed dose of statin ther­a­py. It is al­so un­der re­view by the EMA.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA have vowed not to let politics get in the way of science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped health agencies under his purview — including the FDA — of their rulemaking ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Eli Lilly CSO Dan Skovronsky (file photo)

#ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.

#ES­MO20: As­traZeneca aims to spur PRO­found shift in prostate can­cer treat­ment with Lyn­parza OS da­ta

AstraZeneca has unveiled the final, mature overall survival data that cemented Lynparza’s first approval in prostate cancer approval — touting its lead against rivals with the only PARP inhibitor to have demonstrated such benefit.

But getting the Merck-partnered drug to the right patients remains a challenge, something the companies are hoping to change with the new data cut.

The OS numbers on the subgroup with BRCA1/2 or ATM-mutated metastatic castration-resistant prostate cancer are similar to the first look on offer when the FDA expanded the label in May: Lynparza reduced the risk of death by 31% versus Xtandi and Zytiga. Patients on Lynparza lived a median of 19.1 months, compared to 14.7 months for the anti-androgen therapies (p = 0.0175).

Exelixis CEO Michael Morrissey (file photo)

#ES­MO20: Look out Mer­ck. Bris­tol My­ers and Ex­elix­is stake out their com­bo’s claim to best-in-class sta­tus for front­line kid­ney can­cer

Now that the PD-(L)1 checkpoints are deeply entrenched in the oncology market, it’s time to welcome a wave of combination therapies — beyond chemo — looking to extend their benefit to larger numbers of patients. Bristol Myers Squibb ($BMY} and Exelixis {EXEL} are close to the front of that line.

Today at ESMO the collaborators pulled the curtain back on some stellar data for their combination of Opdivo (the PD-1) and Cabometyx (the TKI), marking a significant advance for the blockbuster Bristol Myers franchise while offering a big leg up for the team at Exelixis.

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Dan Skovronsky, Eli Lilly CSO

An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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#ES­MO20: It’s not just Keytru­da any­more — Mer­ck spot­lights 3 top ear­ly-stage can­cer drugs

Any $12 billion megablockbuster in the portfolio tends to overshadow everything else in the pipeline. Which is something Merck can tell you a little bit about.

Keytruda not only dominates the PD-(L)1 field, it looms over everything Merck does, to the point some analysts wonder if Merck is a one-trick pony.

There’s no shortage of Keytruda data on display at ESMO this weekend, but now the focus is shifting to the future role of new drugs and combos in maintaining that lead position for years to come. And the pharma giant has a special focus for 3 early-stage efforts where Roger Perlmutter’s oncology team is placing some big bets.

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#ES­MO20: Trodelvy da­ta show that Gilead­'s $21B buy­out may have been worth the big pre­mi­um

Gilead CEO Dan O’Day has been on a shopping spree. And while some analysts gawked at the biotech’s recent $21 billion Immunomedics buyout, new data released at virtual ESMO 2020 suggest the acquisition may have been worth the hefty price.

The deal, announced last weekend, will give California-based Gilead $GILD Trodelvy, which was recently approved for metastatic triple-negative breast cancer (mTNBC).

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