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.

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: 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: Alk­er­mes of­fers their first snap­shot of a ben­e­fit for their next-gen IL-2 drug. But why did 1 pa­tient starve to death?

Everyone in the cancer R&D arena is looking to build new franchises around better drugs and combos. And one busy pocket of that space is centered entirely on creating an IL-2 drug that can be as effective as the original without the toxicity that damned it to the sidelines.

Alkermes $ALKS formally tossed its hat into the ring of contenders at virtual ESMO today, highlighting the first glimpse of efficacy for their candidate, ALKS 4230, as both a monotherapy as well as in combination with Merck’s Keytruda.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

Pfiz­er match­es Mod­er­na with their full Covid-19 tri­al blue­print — As­traZeneca says it will un­veil its pro­to­col 'short­ly'

Yesterday, after sustained public pressure as Moderna released its Phase III Covid-19 trial blueprint, Pfizer released its own full trial design for their vaccine trials. The move was designed to boost transparency and shore up public trust in the vaccines, but it also revealed differences in how the two companies are approaching the much-watched studies while failing to satisfy the demands of the fiercest advocates for transparency.

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#ES­MO20: Re­gen­eron, Sanofi eye an­oth­er first for their PD-1 con­tender Lib­tayo with promis­ing da­ta for on­col­o­gy niche

Regeneron and Sanofi took another step forward in the long march towards a greatly expanded market for their late-bloomer PD-1 checkpoint Libtayo.

The two occasional allies posted an objective response rate of 31% for Libtayo among 84 patients suffering from advanced cases of basal cell carcinoma at virtual ESMO. That spotlights progress for 26 patients, 5 of whom had a complete response. The data also reflect a boost in the number of responses seen from the last cut of the numbers.

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Seat­tle Ge­net­ic­s' Astel­las-part­nered ADC nails con­fir­ma­to­ry PhI­II in urothe­lial can­cer

Nine months after Seattle Genetics nabbed an accelerated approval for its Astellas-partnered antibody-drug conjugate Padcev, the partners said the therapy has nailed a confirmatory Phase III, proving its worth in locally advanced or metastatic urothelial cancer.

Padcev, which has widely been tapped as a potential blockbuster, scored improvements in both overall survival and progression-free survival compared to chemotherapy, causing a 30% reduction in risk of death (p = 0.001) and 39% reduction in risk of disease progression or death (p<0.00001).

Albert Bourla, Pfizer CEO (Steven Ferdman/Getty Images)

Pfiz­er ex­ecs con­fi­dent­ly tap their top 10 block­busters-to-be. But what are the chances of sur­viv­ing PhI­II, let alone hit­ting these big peak sales es­ti­mates?

Pfizer’s top executive team doesn’t lack for confidence.

Where many Big Pharmas would be reluctant to put a peak sales figure on their late-stage drugs, Pfizer CEO Albert Bourla has shrugged off the usual diffidence to outline where the pharma giant expects to get $15 billion-plus.

The list, outlined this week during their investor presentations, is topped by 3 drugs in the $3 billion-plus peak sales category. They are:

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Stronger to­geth­er? Boehringer and Mi­rati team to put first KRAS-KRAS com­bo in the clin­ic

Researchers are still waiting to see how much any of the vaunted KRAS drugs now in the clinic can, after decades of preclinical research and some early human studies, help patients. But while they do, two of the leading developers will look to see whether a KRAS-KRAS combo might pose a better shot than any KRAS alone.

Boehringer Ingelheim and Mirati have signed a collaboration to combine Mirati’s closely-watched lead KRAS inhibitor, MRTX849, in a clinical trial with the pan-KRAS blocker that Boehringer has quietly developed with high expectations behind their flashier contenders.

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Stéphane Bancel, Moderna CEO

UP­DAT­ED: 'The biggest in­flec­tion point ever': On R&D day, Mod­er­na CEO Stéphane Ban­cel dou­bles down on vac­cines and lays out a vi­sion for a '40, 50'-drug biotech

The stakes have always been different for Moderna. They didn’t invest more in the Covid-19 vaccine race than Pfizer, Sanofi or AstraZeneca, and they didn’t have more to lose than Novavax — a $100 million biotech that became a $7 billion company virtually overnight. But they had considerably more to gain than anyone.

Born with grand ambitions and the checkbook to match, Moderna spent its first decade of life attracting as many critics of its vision to remake drug development as it did backers. But the pandemic presented a twin opportunity: to prove its technology on a global stage and to give a still-young biotech billions in annual revenue years before anticipated.

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Steve Hurly, Lava CEO

La­va breaks pro­longed si­lence with an $83M Se­ries C and two I/O pro­grams set for the clin­ic

Lava debuted in May of 2018 with $18.9 million, a platform built around something called gamma delta cells and a plan, apparently, of saying nothing else for the next two years. They never announced a program and they did not issue another press release for the next 20 months.

In May, though, the Dutch-American biotech announced a partnership on cancer bispecifics with J&J. And today, CEO Steve Hurly is ready to talk about what they’ve been working on for the last two years in Utrecht and Philadelphia – as well as the $83 million they raised from Novo, Sanofi and others to bring that work into the clinic next year.