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.

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: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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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 help@endpointsnews.com with any issues.

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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Ver­sant-backed Chi­nook gets a $65M launch round for its dis­cov­ery quest in a resur­gent kid­ney field

Versant is once again stepping off the beaten track in biotech to see if they can blaze a trail of their own in a field that has looked too thorny to many investors for years.

The venture group and their partners at Apple Tree are bringing their latest creation out of stealth mode today. Born in Versant’s Inception Sciences’ Chinook Therapeutics is betting that its preclinical take on kidney disease can get an early lead among the companies starting up in the field.

Sir An­drew Dil­lon, NICE's first — and on­ly — chief ex­ec­u­tive to step down next year

Using a laptop borrowed from his former employer, South London’s St George’s Hospital, Sir Andrew Dillon set about establishing NICE — launched by the then health secretary Frank Dobson — in 1999.  On Thursday, the UK cost-effectiveness watchdog said its first and only chief executive — Dillon — is stepping down in March 2020.

Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.