Armed with stel­lar — if niche — PhI­II da­ta, Re­gen­eron steers 'break­through' cho­les­terol drug to post-PC­SK9 wa­ters

Two years af­ter nab­bing a break­through ther­a­py des­ig­na­tion for evinacum­ab, Re­gen­eron has a slate of stel­lar Phase III da­ta to but­tress its case for of­fer­ing the an­ti­body to pa­tients whose LDL cho­les­terol are so out of con­trol that they may need some­thing even stronger than PC­SK9 in­hibitors.

George Yan­copou­los

The drug treats a rare con­di­tion called ho­mozy­gous fa­mil­ial hy­per­c­ho­les­terolemia, or HoFH, in which pa­tients have mu­ta­tions in both copies of ei­ther PC­SK9, LDLR or APOB genes. Re­gen­eron sci­en­tists found two decades ago that the an­giopoi­etin-like pro­tein 3 (ANGPTL3) blocks lipopro­tein li­pase and en­dothe­lial li­pase from reg­u­lat­ing lipopro­tein me­tab­o­lism. By in­hibit­ing this pro­tein, Re­gen­eron’s the­o­ry goes, they can un­leash the en­zymes to bring down the dan­ger­ous­ly high lev­els of LDL cho­les­terol.

Ac­cord­ing to the topline re­sults, it worked — bet­ter than avail­able HoFH ther­a­pies.

In­ves­ti­ga­tors tracked a 49% re­duc­tion in LDL cho­les­terol from base­line among those tak­ing the drug, com­pared to a 2% in­crease for place­bo (p<0.0001). And that’s on top of the oth­er lipid low­er ther­a­pies the pa­tients were al­ready tak­ing, in­clud­ing statins, PC­SK9 in­hibitors, eze­tim­ibe, LDL aphere­sis and lomi­tapi­de. On av­er­age, the ab­solute changes were 132 mg/dL and 3 mg/dL, re­spec­tive­ly (p<0.0001).

That could set it up to treat pa­tients who have failed Repatha, Am­gen’s PC­SK9 in­hibitor, which is ap­proved for the in­di­ca­tion and has pre­vi­ous­ly shown LDL cho­les­terol re­duc­tion of 31%, Cowen an­a­lyst Yaron Wer­ber wrote. Repatha is now priced at $5,850 a year af­ter in­sur­ers won a pric­ing tug-of-war, prompt­ing a 60% dis­count.

More­over, while the 65 pa­tients be­gan the tri­al with av­er­age LDL cho­les­terol lev­els of 255 mg/dL, 47% of those re­ceiv­ing evinacumb saw their mea­sure­ments go down to or be­low the healthy 100 mg/dL thresh­old. In the place­bo (again, plus oth­er ther­a­pies) group, 23% achieved the same (p=0.0203).

No­tably, about a third of the drug arm had the most se­vere form of HoFH — pa­tients who were es­sen­tial­ly not re­spond­ing to any oth­er treat­ments.

Re­gen­eron pres­i­dent and CSO George Yan­copou­los added that the re­sults bode well for an­oth­er on­go­ing tri­al tar­get­ing se­vere, re­frac­to­ry hy­per­c­ho­les­terolemia, which spans both the in­her­it­ed (but het­erozy­gous) and “en­vi­ron­men­tal” forms of the dis­ease. While Pralu­ent, the PC­SK9 drug they share with Sanofi, is ap­proved to treat HeFH, some con­tin­ue to ex­pe­ri­ence per­sis­tent­ly high cho­les­terol de­spite ex­ist­ing lipid man­age­ment ther­a­pies.

“These evinacum­ab Phase 3 re­sults bring hope to those who need it most” is how FH Foun­da­tion founder and CEO Kather­ine Wile­mon put it.

The small size of this pa­tient pop­u­la­tion, though — Re­gen­eron es­ti­mates 1,300 cas­es of HoFH in the US — may fur­ther strain evinacum­ab’s com­mer­cial hopes as pay­ers con­tin­ue to de­bate the val­ue of car­dio­vas­cu­lar ad­vances.

Wer­ber calls the da­ta “high­ly en­cour­ag­ing” and ac­knowl­edges the clin­i­cal need. By his es­ti­mates, US peak sales should reach the range of $200 mil­lion to $400 mil­lion while Eu­rope will bring in sim­i­lar sales num­bers.

So evinacum­ab should be at­trac­tive but the key ques­tion will be what will pay­ers be will­ing to pay for this or­phan seg­ment. This is es­pe­cial­ly rel­e­vant for evinacum­ab giv­en the tremen­dous pric­ing and ac­cess pres­sures that the an­ti-PCKS9 class is fac­ing.

The com­pa­ny ex­pects to be­gin sub­mit­ting da­ta to the FDA in 2020.

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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Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

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FDA to Sarep­ta: Your wide­ly an­tic­i­pat­ed fol­lowup to Ex­ondys 51 is not get­ting an ac­cel­er­at­ed OK for Duchenne MD

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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UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.

The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

Spring­Works seeks $115M to push Pfiz­er drugs across fin­ish line while Sat­suma sells mi­graine play in $86M IPO

SpringWorks and Satsuma — both biotech spinouts that have closed B rounds in April — are loading up with IPO cash to boost their respective late-stage plans.
SpringWorks

Bain-backed SpringWorks is the better-known company of the two, and it’s gunning for a larger windfall of $115 million to add to $228 million from previous financings. In the process, the Stamford, CT-based team is also drawing the curtains on the partnerships it has in mind for the pair of assets it had initially licensed from Pfizer.

Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Data reveal that different racial and ethnic groups — by nature and/or nurture — can respond differently in terms of pharmacokinetics, efficacy, or safety to therapeutics, but this disparity is not necessarily accounted for in clinical trials. A fresh analysis of the last decade of US cancer drug approvals suggests the trend continues, cementing previous research that suggests oncology trials are woefully under-representative of the racial makeup of the real world.

Van­da shares slide af­ter FDA spurns their big end­point and re­jects a pitch on jet lag re­lief

Back in the spring of last year, Vanda Pharmaceuticals $VNDA served up a hot stew of mixed data for a slate of endpoints related to what they called clear evidence that their melatonin sleep drug Hetlioz (tasimelteon) could help millions of travelers suffering from jet lag.

Never mind that they couldn’t get a planned 90 people in the study, settling for 25 instead; Vanda CEO Mihael H. Polymeropoulos said they were building on a body of data to prove it would help jet-lagged patients looking for added sleep benefits. And that, they added, would be worth a major upgrade from the agency as they sought to tackle a big market.