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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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll