Heart at­tack while on Repatha? Am­gen will give you your mon­ey back

Wash­ing­ton, DC —Am­gen has over­come one of the tough­est chal­lenges in car­dio re­search, out­lin­ing a clear health ben­e­fit for its PC­SK9 cho­les­terol drug Repatha. But be­fore pay­ers get a chance to gnaw at the num­bers be­ing put on dis­play to­day, look­ing for holes or find­ing fault with the lev­el of ben­e­fit, the phar­ma gi­ant wants to send them a sim­ple mes­sage: it’s ready to of­fer a ne­go­ti­at­ed truce to get them to drop their de­fens­es and pull out of the trench­es.

Af­ter find­ing ac­cess to Repatha blocked and locked by blan­ket pay­er re­jec­tions, cor­ralling this drug far from the main­stream, Am­gen $AMGN wants to par­lay.

If pay­ers will just con­sid­er the ben­e­fits Am­gen is demon­strat­ing to­day and take down their elab­o­rate bar­ri­ers, com­pa­ny ex­ecs say they are not on­ly will­ing to of­fer a re­fund when the drug fails, they’ll al­so ne­go­ti­ate an­nu­al pay­ment caps and risk shar­ing deals with in­sur­ers so pay­ers can be sure to keep con­trol of their bud­gets.

Sean Harp­er, EVP Re­search and De­vel­op­ment

Drug re­funds have be­gun to make their way in­to the sys­tem, but they’re still rare enough to make this a stand­out pro­pos­al for a man­u­fac­tur­er try­ing to es­tab­lish a big drug.

“We will work with pay­ers if they’re will­ing to just stop block­ing pa­tients from get­ting the drug,” Sean Harp­er, head of R&D at Am­gen, tells me.

Harp­er and his team showed up at Amer­i­can Col­lege of Car­di­ol­o­gy con­fer­ence in Wash­ing­ton DC on Fri­day to lay their case out with some pi­o­neer­ing da­ta. Study­ing this drug in 27,564 pa­tients over two years, re­searchers say, Repatha was able to low­er a com­pos­ite of car­dio risks by an av­er­age of 20%. And the im­prove­ment in­creased with time, grow­ing from a 16% risk ad­van­tage in year one to 25% af­ter 12 months.

That’s large enough to hit key end­points, but it’s al­so small enough to leave many an­a­lysts won­der­ing if this drug can ever make it to big block­buster sta­tus, which Am­gen is cer­tain it de­serves.

Break­ing down the da­ta, which every­one will do, re­searchers not­ed a 27% re­duc­tion in the risk of heart at­tacks, a 21% risk re­duc­tion for stroke and a 22% re­duc­tion on coro­nary revas­cu­lar­iza­tion. But sig­nif­i­cant­ly there was no im­pact on mor­tal­i­ty or un­sta­ble angi­na.

This was the first time that a tri­al has shown a clear car­dio ben­e­fit from PC­SK9 in­hi­bi­tion.

Sums up Harp­er: “This is huge that we can do this.”

In­vestors, though, were clear­ly not im­pressed. Am­gen’s shares were down 6% af­ter the head­lines hit. And this Tweet should give you a fla­vor for what’s dri­ving the skep­ti­cism:

Umer Raf­fat at Ever­cor­eISI not­ed that most of in­vestors were look­ing for a mor­tal­i­ty ben­e­fit and were clear­ly dis­ap­point­ed in not see­ing one. Am­gen’s bull­ish­ness on the da­ta ahead of the de­tails al­so in­flat­ed ex­pec­ta­tions. And the same bit­ter taste al­so ex­tend­ed to the rest of the play­ers in the field, in­clud­ing Re­gen­eron $REGN and Sanofi $SNY, which both got hit, as well as The Med­i­cines Com­pa­ny {$MD­CO -20%} which has a next-gen ther­a­py in the clin­ic it’s been see­ing suc­cess with.

Baird’s Bri­an Sko­r­ney called it a let down. He added:

The pri­ma­ry end­point just hit stat sig with a HR of 0.85 (be­low ex­pec­ta­tions), while the MACE sec­ondary end­point saw a 20% risk re­duc­tion (in-line). Even more dis­ap­point­ing, CV death failed to sep­a­rate from place­bo. Though we do think that to­day’s da­ta is ev­i­dence that PC­SK9 in­hi­bi­tion works, the ben­e­fit isn’t as pro­found as in­vestors were look­ing for and pay­ers are like­ly to lever­age this dis­ap­point­ment.

Am­gen has bet big on Repatha, bankrolling sev­er­al huge stud­ies to demon­strate the drug’s abil­i­ty to dra­mat­i­cal­ly slash LDL lev­els, which its in­ves­ti­ga­tors say is clear­ly a tox­in. Now it has a win on car­dio out­comes to make its point to physi­cians and a large po­ten­tial pa­tient pop­u­la­tion. But the tri­al suc­cess is not big enough by it­self to get pay­ers to stop re­ject­ing pre­scrip­tions “over and over and over again,” as Harp­er de­scribes the treat­ment to date.

Joshua J. Of­man, Am­gen

“The process on uti­liza­tion man­age­ment has been bro­ken,” says Am­gen val­ue man­age­ment chief Joshua J. Of­man. Ever since 2013’s in­tro­duc­tion of So­val­di pay­ers have been up­ping their game, fig­ur­ing out new ways to stop their mem­bers from get­ting ac­cess to new drugs like this. And in Repatha’s case, pay­ers are in over­drive, forc­ing physi­cians to go back and file over and over again.

The num­bers Am­gen is re­port­ing to­day are al­so be­ing pitched as far more con­ser­v­a­tive than what pa­tients see in the re­al world. All the pa­tients in the study got the best stan­dard of care, which is some­thing you won’t see in the re­al world. And Am­gen is hap­py to ne­go­ti­ate its next round of con­tracts based on re­al-world ex­pec­ta­tions.

So now Am­gen says they’ll guar­an­tee a low­er risk of heart at­tack and re­fund the cost of the drug for any pa­tient who has a heart at­tack. They’ll still come out well ahead if they can reach the at-risk pop­u­la­tion whose LDL lev­els can­not be con­trolled by cheap statins.

Am­gen’s full court press on Repatha has in­clud­ed a co­or­di­nat­ed at­tack on its big ri­val Pralu­ent from Re­gen­eron and Sanofi. At one point re­cent­ly a judge’s rul­ing threat­ened to push the com­pet­ing drug off the mar­ket as Am­gen — a ma­jor league lit­i­ga­tor — pressed its ar­gu­ment that Pralu­ent vi­o­lat­ed its PC­SK9 patents. But the part­ners man­aged to block that, for now.

Next up: Car­dio da­ta from Re­gen­eron and Sanofi. So far, these drugs have ap­peared very sim­i­lar, and it wouldn’t sur­prise many ob­servers if their com­peti­tor comes on around the same score. But every da­ta point will get care­ful scruti­ny as the gi­ants block and tack­le in search of every small ad­van­tage, while hop­ing to achieve a break­through on mar­ket­ing that can fi­nal­ly gen­er­ate some big num­bers.

So far, it’s not look­ing good.

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.
Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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:

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,000+ biopharma pros reading Endpoints daily — and it's free.

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.”