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.

John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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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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Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.