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.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

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As­traZeneca scores new goal on the pipeline front, adding its first AI-gen­er­at­ed tar­get to the port­fo­lio

As more and more biopharmas develop artificial intelligence platforms, the drug discovery process is being reshaped to fit new goals on cutting down the prodigious amount of time, energy and money that go into a drug program. Now one of the most ambitious players in the drive to improve on ROI, AstraZeneca, is marking a milestone on that front by adding the first target generated by AI to its portfolio.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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