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.

Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

George Yancopoulos (Regeneron)

Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er shares surge on pos­i­tive im­pact of their mR­NA Covid-19 vac­cine — part­nered with BioN­Tech — in an ear­ly-stage study

Pfizer and their partners at the mRNA specialist BioNTech have published the first glimpse of biomarker data from an early-stage study spotlighting the “robust immunogenicity” triggered by their Covid-19 vaccine, which is one of the leaders in the race to vanquish the global pandemic.

Researchers selected 45 healthy volunteers 18-55 years of age for the study. They were randomized to receive 2 doses, separated by 21 days, of 10 µg, 30 µg, or 100 µg of BNT162b1, “a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD.” Their responses were compared against the effect of a natural, presumably protective defense offered by a regular infection.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Pos­i­tive Covid-19 vac­cine da­ta? New mouse study? OWS in­clu­sion? Yep, but some­how, the usu­al tid­bits from In­ovio back­fire

You don’t go more than 40 years in biotech without ever getting a product to market unless you can learn the art of writing a promotional press release. And Inovio captures the prize in baiting the hook.

Tuesday morning Inovio, which has been struggling to get its Covid-19 vaccine lined up for mass manufacturing, put out a release that touched on virtually every hot button in pandemic PR.

There was, first and foremost, an interim snapshot of efficacy from their Phase I program for INO-4800.

Jan van de Winkel, Genmab CEO

Seat­tle Ge­net­ics, Gen­mab turn on TV for a high­light reel in cer­vi­cal can­cer — but a ri­val biotech promis­es a bet­ter show

Seattle Genetics $SGEN and their partners at Genmab $GMAB polished up some positive Phase II numbers for their antibody drug conjugate tisotumab vedotin — you can call it TV — for recurrent cervical cancer. And while they mapped out a shortcut to a potential quick approval, the big challenge for this team is being presented by a rival biotech which muscled its way into the spotlight for the same indication a year ago.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 84,700+ biopharma pros reading Endpoints daily — and it's free.

Randy Schatzman, Bolt CEO (Bolt Biotherapeutics)

Bolt Bio­ther­a­peu­tics nabs $93.5M to push Provenge in­ven­tor's new idea deep­er in the clin­ic

A cancer-fighting concept from the inventor of the first cancer vaccine is nearing prime time, and its biotech developer has received a significant new infusion of cash to get it there.

Bolt Biotherapeutics announced a $93.5 million Series C round led by Sofinnova Investments and joined by more than 9 others, including Pfizer Ventures and RA Capital Management. That money will go toward pushing the San Francisco biotech’s platform of innate immune-boosting warheads through its first trial on metastatic solid tumors and into several more.

Days af­ter In­ter­cept re­jec­tion, Akero surges on ‘un­prece­dent­ed‘ NASH da­ta

A year and a half after scoring a $70 million Series B and a top Gilead executive as CEO, Akero Therapeutics has announced new data on their NASH drug. And with the field still reeling from a surprise FDA rejection this week, the news was enough to send their stock surging.

Akero had already said in March that its lead drug had beaten placebo in its Phase II trial, reducing liver fat by 14% in the highest dose group compared to 0.3% in placebo, according to MRI scans. But although NASH is an obesity-related condition and results from fatty buildup in the liver, the real immediate question for any therapy is whether it can resolve the fibrosis and inflammation that results from that buildup. Those data require biopsying the patients, a longer and more invasive process that was further complicated by a pandemic.