Flanked by ri­vals and skep­tics, Es­pe­ri­on flips pos­i­tive da­ta on first PhI­II for a po­ten­tial­ly game-chang­ing cho­les­terol pill

Es­pe­ri­on $ES­PR is rolling out its first pos­i­tive da­ta set from a slate of piv­otal late-stage stud­ies of its LDL-low­er­ing drug be­mpe­doic acid this morn­ing — one of the most close­ly fol­lowed pro­grams in the busi­ness.

Fac­ing a skep­ti­cal au­di­ence of pay­ers and ri­vals — which have al­ready shown they can do much, much bet­ter with the same tar­get — Es­pe­ri­on post­ed a 28% spread against a place­bo, with a 23% drop in LDL-c for the drug plus eze­tim­ibe against a 5% in­crease for pa­tients in the place­bo group.

In­ves­ti­ga­tors al­so tracked an­oth­er plus for statin in­tol­er­ant pa­tients, with a 32% drop in high-sen­si­tiv­i­ty C-re­ac­tive pro­tein, a mark­er for dam­ag­ing in­flam­ma­tion which can have se­ri­ous longterm con­se­quences for car­dio health.

“In both cas­es,” CEO Tim Mayleben tells me as he set the stage for to­day’s an­nounce­ment, “this study ex­ceed­ed ex­pec­ta­tions.”

But is that enough?

It’s all sta­tis­ti­cal­ly sig­nif­i­cant, giv­ing sup­port­ive an­a­lysts the da­ta they were look­ing for to cel­e­brate the first of 5 Phase III stud­ies due out by the fall, set­ting up a mar­ket­ing pitch to the FDA in Q1 2019. Based on the da­ta, there are good rea­sons to be­lieve that the biotech can come through with more pos­i­tive ef­fi­ca­cy da­ta and a clean bill of health on liv­er tox.

But there’s a lot more in­volved here than demon­strat­ing that a new drug can beat out a place­bo. That’s been done be­fore. Es­pe­ri­on has to con­vince every­one that its new LDL low­er­ing pill can suc­ceed where oth­er drugs — in­jecta­bles — with much bet­ter re­sults have fared poor­ly thus far. In the car­dio field, as Mer­ck demon­strat­ed with its re­cent de­ci­sion to jet­ti­son a CETP ther­a­py in the wake of a win against a place­bo, pos­i­tive da­ta is no guar­an­tee of suc­cess. It al­so has to be com­mer­cial­ly vi­able, able to con­vince the mar­ket that this drug can break in­to block­buster ter­ri­to­ry.

Be­mpe­doic acid in dif­fer­ent com­bi­na­tions has al­so scored high­er in mid-stage stud­ies. But Es­pe­ri­on de­signed this first, crit­i­cal study to add their drug af­ter a round of eze­tim­ibe, mim­ic­k­ing the re­al world en­vi­ron­ment where doc­tors will be look­ing to fol­low up on statin re­sis­tance af­ter first try­ing a gener­ic at a very, very low cost.

Mayleben has al­ready bro­ken the car­di­nal rule of drug de­vel­op­ment, nam­ing a price of about $9 to $10 a day — or in the $3,500 per year range — well ahead of a launch.

That just doesn’t hap­pen in bio­phar­ma, where the vir­tu­al law of drug mar­ket­ing re­quires that the price be kept un­der lock­down un­til af­ter a mar­ket­ing OK comes through for a new drug — es­pe­cial­ly if de­vel­op­ers know per­fect­ly well what they will sell it for.

The Es­pe­ri­on CEO, though, can’t play by those rules. He has to steer a course around PC­SK9 drugs from Re­gen­eron/Sanofi and Am­gen, which eas­i­ly outscore his ther­a­py on low­er­ing LDL. Mayleben’s tar­get will be a wide range of pa­tients who need to see a big drop in LDL, but don’t nec­es­sar­i­ly re­quire the axe PC­SK9 brings to the ta­ble — and who don’t want any part of the $14,000 an­nu­al price tag at­tached that has spurred pay­ers to throw up a com­plex set of hur­dles to pre­vent wide­spread use.

That re­quires a will­ing­ness to up­set some ap­ple carts along the way. Stick­ing with the in­dus­try stan­dard here won’t help the roll out he’s plan­ning, with some an­a­lysts set­ting peak sales es­ti­mates deep in­to block­buster ter­rain.

“Why should this not be the way things are?” asks the CEO.

He cit­ed the out­cry that met Gilead when they priced their pi­o­neer­ing hep C cure at $84,000 as an ex­am­ple of what can go wrong.

“The is­sue was not just the price, but it was above ex­pec­ta­tions,” he notes. Flag­ging the price and start­ing that dis­cus­sion well ahead of a launch just makes sense.

Mayleben adds: “I don’t think I re­al­ized that we were set­ting any sort of prece­dent with what we were do­ing.”

Es­pe­ri­on, though, doesn’t have the lux­u­ry of a break­through drug, in the same way that the PC­SK9s or So­val­di were able to en­joy. To com­pete will take some dis­rup­tive rule break­ing.

And Mayleben plans to do just that.

There are 4 more piv­otal stud­ies to come. And Es­pe­ri­on is bring­ing on a chief com­mer­cial of­fi­cer soon to start lay­ing the foun­da­tion for a com­mer­cial wing. At some point, Mayleben isn’t say­ing when, the com­pa­ny al­so wants to bring in com­mer­cial part­ners to help roll out a mass mar­ket ef­fort in ear­ly 2020. And then they’ll still have to wait for car­dio out­comes da­ta in 2022.

The 2018 da­ta sea­son has be­gun for Es­pe­ri­on, and there’s vir­tu­al­ly no wig­gle room in the course the biotech has to steer now.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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UP­DAT­ED: CMS to re­strict cov­er­age of Bio­gen's con­tro­ver­sial Alzheimer's drug to on­ly clin­i­cal tri­als

The Centers for Medicare and Medicaid Services on Tuesday said it will only pay for Biogen’s Aduhelm and other FDA-approved anti-amyloid monoclonal antibodies for Alzheimer’s disease under CMS-approved randomized controlled trials.

The draft national coverage decision, which insurers nationwide are likely to follow, makes clear that CMS will be looking for randomized controlled trials that “demonstrate a clinically meaningful benefit in cognition and function.” That will be a tough task for Biogen, which previously showed conflicting benefits from past Aduhelm trials that were initially cut short due to futility and then resurrected for the accelerated approval.

CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.