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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Albert Bourla, Pfizer CEO (Efren Landaos/Sipa USA/Sipa via AP Images)

Pfiz­er makes an­oth­er bil­lion-dol­lar in­vest­ment in Eu­rope and ex­pands again in Michi­gan

Pfizer is continuing its run of manufacturing site expansions with two new large investments in the US and Europe.

The New York-based pharma giant’s site in Kalamazoo, MI, has seen a lot of attention over the past year. As a major piece of the manufacturing network for Covid-19 vaccines and antivirals, Pfizer is gearing up to place more money into the site. Pfizer announced it will place $750 million into the facility, mainly to establish “modular aseptic processing” (MAP) production and create around 300 jobs at the site.

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Vas Narasimhan, Novartis CEO (Thibault Camus/AP Images, Pool)

No­var­tis bol­sters Plu­vic­to's case in prostate can­cer with PhI­II re­sults

The prognosis is poor for metastatic castration-resistant prostate cancer (mCRPC) patients. Novartis wants to change that by making its recently approved Pluvicto available to patients earlier in their course of treatment.

The Swiss pharma giant unveiled Phase III results Monday suggesting that Pluvicto was able to halt disease progression in certain prostate cancer patients when administered after androgen-receptor pathway inhibitor (ARPI) therapy, but without prior taxane-based chemotherapy. The drug is currently approved for patients after they’ve received both ARPI and chemo.

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Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Yuling Li, Innoforce CEO

In­no­force opens new man­u­fac­tur­ing site in Chi­na

Innoforce is off to the races at its new site in the city of Hangzhou, China.

The Chinese CDMO announced last week that it has started manufacturing at the new facility, which was built to offer process development and manufacturing operations for RNA, plasmid DNA, viral vectors and other cell therapeutics. It will also serve as Innoforce’s corporate HQ.

The company said it’s investing more than $200 million in the 550,000-square-foot manufacturing base for advanced therapies. The GMP manufacturing facility features space for producing plasmids with three 30-liter bioreactors. For viral vector manufacturing, Innoforce also has 200- and 500-liter bioreactors at its disposal, along with eight suites to make cell therapies. The site also includes several labs and warehouse spaces.

FDA grants or­phan drug des­ig­na­tion to Al­ger­non's ifen­prodil, while ex­clu­siv­i­ty re­mains un­clear

As the FDA remains silent on orphan drug exclusivity in the wake of a controversial court case, the agency continues to hand out new designations. The latest: Algernon Pharmaceuticals’ experimental lung disease drug ifenprodil.

The Vancouver-based company announced on Monday that ifenprodil received orphan designation in idiopathic pulmonary fibrosis (IPF), a chronic lung condition that results in scarring of the lungs.  Most IPF patients suffer with a dry cough, and breathing can become difficult.

‘Catchy’ de­sign tops big ad buys on­line for grab­bing on­col­o­gists’ at­ten­tion — sur­vey

The cancer drug ads that get oncologists’ attention online are informative and use clear, eye-catching designs. That’s ZoomRx’s assessment in its most recent tracking survey, and while not necessarily surprising, the details in the research do break a few common misconceptions.

One of those is frequency, also known as the number of impressions an ad gets. No matter how many times oncologists saw a particular cancer drug ad, effectiveness prevailed in the survey across five drug brands. ZoomRx measured effectiveness as a combination of most attention-getting, relevant information and improved perception as reported by the doctors.

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Tim Walbert, Horizon Therapeutics CEO (via YouTube)

And then there were two: Janssen bows out of Hori­zon takeover ne­go­ti­a­tions

Horizon Therapeutics announced last week that it was in talks with three pharmaceutical giants that could take over the company. You can now remove one of them from the equation.

J&J’s Janssen, after Horizon reported its initial involvement in early discussions to acquire the rare disease biotech, issued a statement Saturday that said Janssen “does not intend to make an offer for Horizon,” and that Janssen is bound by restrictions set in Rule 2.8 of the Irish Takeover Rules. These rules are in place for any company interested in taking over Irish companies, with Horizon Therapeutics currently based in Dublin.

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Nkarta CEO Paul Hastings at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Nkar­ta un­der­scores safe­ty of CAR-NK, boasts ear­ly re­spons­es

The first generation of personalized CAR-T therapies made big waves in the treatment of lymphoma for their stunning efficacy. Nkarta is hoping its off-the-shelf natural killer cell approach will stand out on safety — while keeping some of those impressive numbers on responses.

In a new update from its Phase I dose escalation study, the South San Francisco-based biotech reported that seven out of 10 patients treated with the highest doses of its NK cell therapy, NKX019, achieved a complete response, translating to a complete response rate of 70%.