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.

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

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Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

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Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

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Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.

S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Mod­er­na's Stéphane Ban­cel plans to dou­ble down on vac­cine pro­duc­tion, new vari­ants as mR­NA rules in pan­dem­ic fight

Stéphane Bancel thought he’d be sleeping more by now.

The 48-year-old Moderna CEO figured that by 2021 he’d have his vaccine through the clinic, authorized, and in mass production — that the hard part would be over. Instead, he’s still working Saturdays and Sundays, talking with his lab and manufacturing teams and fielding calls with two to three world leaders a day to answer their concerns about supply and emerging new variants.

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FDA re­view­ers en­dorse J&J sin­gle-dose shot, lay­ing path for 3rd US vac­cine

J&J’s single-dose vaccine may not have produced quite the stellar numbers of the mRNA shots, but it still won a ringing endorsement from FDA reviewers, who argued in briefing documents that it could provide robust protection against the still-raging virus.

The FDA confirmed that across just under 40,000 volunteers, the vaccine proved 66% effective at preventing symptomatic Covid-19, including 72% effective in the United States. Although that’s short of the 95% figures put up by Moderna and Pfizer-BioNTech, the shot was still 85% effective at stopping severe disease 28 days after administration. There were seven deaths in the placebo group — zero in the vaccine group.

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