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.

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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David de Graaf now has his $28.5M launch round in place, build­ing a coen­zyme A plat­form in his lat­est start­up

Long­time biotech ex­ec David de Graaf has the cash he needs to set up the pre­clin­i­cal foun­da­tion for his coen­zyme A me­tab­o­lism com­pa­ny Comet. A few high-pro­file in­vestors joined the ven­ture syn­di­cate to sup­ply Comet with $28.5 mil­lion in launch mon­ey — enough to get it two years in­to the plat­form-build­ing game, with­in knock­ing dis­tance of the clin­ic.

Canaan jumped in along­side ex­ist­ing in­vestor Sofinno­va Part­ners to co-lead the round, with par­tic­i­pa­tion by ex­ist­ing in­vestor INKEF Cap­i­tal and new in­vestor BioIn­no­va­tion Cap­i­tal.

Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Step­ping on Roche's toes, Mer­ck cuts in­to SCLC niche with third-line Keytru­da OK

In the in­creas­ing­ly crowd­ed check­point race, small cell lung can­cer has been a rare area where Roche, a sec­ond run­ner-up, has a lead over the en­trenched lead­ers Mer­ck and Bris­tol-My­ers Squibb. But Mer­ck is fi­nal­ly mak­ing some head­way in that di­rec­tion with the lat­est ap­proval for its PD-1 star.

The lat­est green light en­dors­es Keytru­da in the third-line treat­ment of metasta­t­ic SCLC, where it would be giv­en to pa­tients whose dis­ease ei­ther don’t re­spond to or re­lapse af­ter chemother­a­py, which would have fol­lowed at least one pri­or line of ther­a­py.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.

UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.

In­vestors fret as VBI's hep B vac­cine fails key sec­ondary PhI­II study goal

Sobered by mount­ing costs, Dy­navax $DVAX last month made the de­ci­sion to fo­cus all its re­sources on its 2017-ap­proved he­pati­tis B vac­cine Hep­lisav-B, which ri­vals and su­per­sedes the ef­fi­ca­cy and con­ve­nience pro­file of GSK’s $GSK es­tab­lished En­ger­ix-B. The Cal­i­for­nia-based com­pa­ny will be on the look­out for an­oth­er com­peti­tor — VBI Vac­cines, which on Mon­day un­veiled late-stage da­ta on its hep B vac­cine: Sci-B-Vac.

Image: Shutterstock

Gene ther­a­py R&D deals turn red hot as Big Phar­ma steps up to play

This September will mark the 20th anniversary of the death of Jesse Gelsinger, a young man suffering from X-linked genetic disease of the liver. He was killed in a gene therapy study conducted by Penn’s James Wilson, and the entire field endured a lengthy deep freeze as the field grappled with the safety issues inherent in the work.

Some thought gene therapy R&D would never survive. But it did. And this year marked a landmark approval for Zolgensma, a new gene therapy for spinal muscular atrophy Novartis priced at $2.1 million.

“Gene therapy is the hottest item on the block now. But there was a time when we first got into this trial, where there wasn’t a person in the world who believed that gene therapy would work. We have to remember that,” noted gene therapy investigator Jerry Mendell told SMA News Today.

We’re still right on the pioneering frontier when it comes to getting approvals for gene therapies and launching marketing campaigns with the European green light for bluebird's leading program last Friday underscoring the nascent nature of the field. But gene therapy R&D is booming, and has been for several years now.

The rapid growth of gene therapy clinical development is well known, but we decided to put some numbers on it, to quantify what’s going on. DealForma chief Chris Dokomajilar took a lot over the past 10 years, as the number of deals, R&D partnerships and buyouts steadily gained steam, spiking last year and on track to maintain the surge in 2019.

The upfronts and totals for the dollars on deals so far in 2019 is already close to the 2018 mark, underscoring a new phase of negotiations as the major players step up to gain a piece of the late-stage and commercial action.

Once again, we’re looking at an “overnight” biotech success story, decades in the making.

At some point, that may start to brake the numbers we’re seeing. But for now, as rivals line up to compete for frontline prominence across a range of diseases, the arrows are all pointed north.

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Albert Bourla appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

UP­DAT­ED: Pfiz­er CEO Al­bert Bourla is back in the M&A game, but why is he pay­ing $11.4B for Ar­ray?

Pfiz­er $PFE has cut short its time on the side­lines of bio­phar­ma M&A.

Mon­day morn­ing the phar­ma gi­ant un­veiled an $11.4 bil­lion deal to ac­quire Ar­ray Bio­Phar­ma, beef­ing up its on­col­o­gy work and adding a new re­search hub in Boul­der, Col­orado to its glob­al op­er­a­tions.

At $48 a share, Ar­ray $AR­RY in­vestors will be get­ting a 62% pre­mi­um off the Fri­day close of $29.59.

Pfiz­er, which has strug­gled to gain all the up­side promised in past buy­outs like Medi­va­tion, high­light­ed the ac­qui­si­tion of 2 ap­proved drugs in the deal — Braftovi (en­co­rafenib) and Mek­tovi (binime­tinib).

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