Es­pe­ri­on of­fers an­oth­er up­beat cut of piv­otal cho­les­terol da­ta for their com­bo, bumps back read­out for key safe­ty study

Over the past few months Es­pe­ri­on $ES­PR has been grad­u­al­ly dig­ging out of the hole it found it­self in af­ter a small im­bal­ance of deaths in a re­cent cho­les­terol study trig­gered an alarm for some of the an­a­lysts cov­er­ing the com­pa­ny. And the com­pa­ny’s ex­ecs will be keep­ing their fin­gers crossed this morn­ing that in­vestors will re­main sat­is­fied with their lat­est set of Phase III da­ta in the buildup to a mar­ket­ing ap­pli­ca­tion and an­tic­i­pat­ed roll­out next year.

But there are no guar­an­tees for this com­pa­ny, which to­day al­so sig­naled that it is bump­ing back the read­out on its big, piv­otal safe­ty tri­al to Oc­to­ber, push­ing back from a planned show­down next month as Au­gust proved a tough month to get all pa­tients in for their fi­nal vis­it.

Tim Mayleben

Es­pe­ri­on’s sup­port­ing cast on Wall Street can be ex­pect­ed to nod ap­prov­ing­ly as a fixed dose com­bi­na­tion of their be­mpe­doic acid with a shot of Ze­tia hit an added 35% re­duc­tion in LDL (on top of statins) for the on-treat­ment ef­fect at 12 weeks — 32% in the in­tent-to-treat analy­sis. That com­pares to 24% for eze­tim­ibe and 20% for be­mpe­doic acid.

In the ITT analy­sis that scored 21% for Ze­tia and 18% for BA. Place­bo re­spons­es were neg­li­gi­ble, al­low­ing for a com­pelling p val­ue on ef­fi­ca­cy (p=0.001).

But what about safe­ty, where all eyes are on any kind of threat?

Where Es­pe­ri­on got in­to trou­ble in the spring was a slight im­bal­ance in the rate of death be­tween their drug arm and the place­bo group — 13 to 2 — even though none of the deaths were di­rect­ly linked to the drug and no one changed or halt­ed the study. Sta­tis­ti­cal­ly, that may have been noth­ing more than an un­lucky drop of the cards — sta­tis­ti­cal­ly in­signif­i­cant — but Es­pe­ri­on faces its own unique stan­dards on suc­cess that are craft­ed for each hur­dle.

In this lat­est tri­al re­searchers tracked se­ri­ous ad­verse events, but they evened out among the ther­a­peu­tic dos­es, with 8% in the fixed dose arm, 6% for BA, 9% for Ze­tia and 2% in the sug­ar pill arm. But there were no fa­tal­i­ties.

Es­pe­ri­on re­searchers al­so tracked a 34% re­duc­tion in C-re­ac­tive pro­tein for the com­bo — a key safe­ty bio­mark­er though well short of an out­comes ben­e­fit — com­pared to an in­crease in the place­bo group of 4% and re­duc­tions of 20% for BA and 9% for EZE.

“We’re the lipid man­age­ment ex­perts,” says Es­pe­ri­on CEO Tim Mayleben, who sees his chief task right now as ed­u­cat­ing the field on what the da­ta in­di­cate. Priced right, Mayleben and his crew be­lieve that they can make their drug the top choice for mil­lions of pa­tients who don’t do well enough on cheap gener­ic statins but al­so don’t need the full weight of a more ex­pen­sive PC­SK9 drug.

PC­SK9 lead­ers Am­gen, Re­gen­eron and Sanofi, though, are do­ing all they can to un­der­cut that mar­ket, squeez­ing Es­pe­ri­on with low­er prices.

Now in­vestors will be wait­ing un­til Oc­to­ber to find out more about Study 2, which will pro­vide 52-week safe­ty re­sults on a large group of pa­tients. That will set the stage for a mar­ket­ing pitch on both the monother­a­py as well as the com­bi­na­tion, Mayleben tells me. The on­ly oth­er study is its big out­comes study in 2022, which Es­pe­ri­on be­lieves won’t be re­quired ahead of a green reg­u­la­to­ry light.

That still presents a big hur­dle, how­ev­er.

Pay­ers have set a high bar for cho­les­terol drugs, leav­ing Es­pe­ri­on at work try­ing to thread the nee­dle on ef­fi­ca­cy — where PC­SK9 drugs can do bet­ter — and safe­ty, where any hand­i­cap is seen as a po­ten­tial deal killer with in­sur­ers who may well not like the idea of see­ing mil­lions of pa­tients grav­i­tate to a pricey new brand­ed drug.

Their see-saw bat­tle for prov­ing ef­fi­ca­cious enough to al­low the com­pa­ny to shoot for a sweet spot where every­one can be sat­is­fied with a less ex­pen­sive al­ter­na­tive to PC­SK9 will keep the de­bate alive right up un­til the com­pa­ny gets a de­ci­sion on its mar­ket­ing ap­pli­ca­tion. Even af­ter that, the stock could re­main a volatile se­cu­ri­ty.

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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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: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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