Pralu­ent Odyssey: Re­gen­eron/Sanofi gun for mar­ket break­out with first-ever mor­tal­i­ty ben­e­fit — and a big price dis­count

Few drug ri­val­ries have been car­ried out with more di­rect, hand-to-hand fight­ing than the scrap over the PC­SK9 mar­ket. Mar­gin­al as the mar­ket is now, the com­bined forces of Re­gen­eron and Sanofi al­lied against Am­gen have nev­er­the­less punched it out in court and the play­ing field in the de­vout be­lief that bil­lions are at stake. And all three have had to strug­gle with a pay­ers’ back­lash against the two drugs they’re sell­ing.

Now Re­gen­eron/Sanofi are launch­ing a full scale as­sault, armed with new da­ta from the 18,924-pa­tient Odyssey Out­comes study high­light­ing ground­break­ing ev­i­dence of a mor­tal­i­ty ben­e­fit for Pralu­ent that they be­lieve will give them an edge. And they’re fol­low­ing through by dra­mat­i­cal­ly mark­ing down the pub­lic price they are propos­ing to charge for pay­ers will­ing to fi­nal­ly dis­man­tle the hur­dles they’ve erect­ed to stop their mem­bers from tak­ing their cho­les­terol treat­ment.

Just as Am­gen won ku­dos for its work to con­vince pay­ers to do the same with mon­ey-back guar­an­tees, this new round marks the in­dus­try’s in­creas­ing will­ing­ness to ne­go­ti­ate over what it charges — a trend that is cre­at­ing a sea change over some drugs that have to sur­vive in a com­pet­i­tive scene.

First, here’s the long-await­ed Odyssey Out­comes da­ta, re­leased at the Amer­i­can Col­lege of Car­di­ol­o­gy’s sci­en­tif­ic meet­ing in Or­lan­do.

Re­searchers say they have con­clu­sive ev­i­dence that Pralu­ent not on­ly sig­nif­i­cant­ly re­duced the num­ber of car­dio in­ci­dents ex­pe­ri­enced by pa­tients on the LDL drug, with the vast ma­jor­i­ty al­so on high-in­ten­si­ty statins, they al­so have a clear re­duc­tion in deaths — the goal that elud­ed Am­gen when it float­ed their Fouri­er da­ta last sum­mer.

— Look­ing at MACE (Ma­jor Ad­verse Car­diac Events) among pa­tients with an LDL lev­el over 100 mg/dL, there was a drop of 3.4 points be­tween the place­bo arm and Pralu­ent rates — 14.9% to 11.5%, a risk re­duc­tion of 24%.

— For CV death the rate dropped from 4.2% to 2.9%.

— And for all-cause deaths the de­crease was 5.7% to 4.1%, with a 1.7 point drop; a 29% drop in risk.

To put it an­oth­er way, for every 1,000 pa­tients who met this pro­file and were on drug, 17 peo­ple would still be alive. And that, say the part­ners, should be the telling dif­fer­ence for pay­ers.

To dri­ve that mes­sage home, Sanofi to­day has agreed to cut their price of Pralu­ent to $4,460 to $7,975 a year for pay­ers who are will­ing to stop throw­ing up road­blocks to this drug, drop­ping to a price that on the low end is not much high­er than the $10-a-day cost of the old gen­er­a­tion of statins be­fore they went gener­ic. At the high end, it still marks a sharp drop from the $14,000 whole­sale price that had been the mar­ket stan­dard used to peg dis­counts against.

“Too many pa­tients in ur­gent need of ad­di­tion­al treat­ment op­tions on top of statins have faced tremen­dous hur­dles to gain ac­cess to this im­por­tant med­i­cine. We are pre­pared to change this by im­prov­ing ac­cess and af­ford­abil­i­ty, elim­i­nat­ing these bur­den­some bar­ri­ers for high-risk pa­tients in need,” said Sanofi CEO Olivi­er Brandi­court in a state­ment. “We will be­gin work­ing with pay­ers to en­sure that high-risk pa­tients have ap­pro­pri­ate ac­cess. This is the right thing to do for pa­tients.”

That was not an easy con­ces­sion for Sanofi, but these drugs are earn­ing on­ly a frac­tion of what an­a­lysts had ex­pect­ed.

At this point, there’s vir­tu­al­ly no ques­tion that these drugs work as billed, slash­ing LDL lev­els safe­ly. In fact, many an­a­lysts would al­so tell you that they are re­mark­ably sim­i­lar. Per­haps they were a lit­tle too sim­i­lar for a judge who once or­dered Re­gen­eron and Sanofi to yank their drug dur­ing their court bat­tle with Am­gen over the patents in­volved. That rul­ing was over­turned, but the le­gal fight con­tin­ues.

Re­gen­eron/Sanofi are com­ing out with a dif­fer­en­ti­at­ed pro­file now, though, af­ter Am­gen hus­tled its Repatha out­comes da­ta out last year, trum­pet­ing sig­nif­i­cant re­duc­tions in car­dio events but no mor­tal­i­ty ben­e­fit. And pay­ers re­mained unim­pressed.

Why did Odyssey Out­comes suc­ceed on that mor­tal­i­ty score?

Bob Pordy, the vice pres­i­dent of car­dio­vas­cu­lar and me­tab­o­lism ther­a­peu­tics at Re­gen­eron, says you can mark that down to the fact they fo­cused on a group of ACS pa­tients who were by far at the high­est risk, with a sig­nif­i­cant­ly longer du­ra­tion of treat­ment in the study.

“Odyssey Out­comes stud­ied Pralu­ent in the high­est risk pa­tients,” echoes Jay Edel­berg, Sanofi’s head of car­dio de­vel­op­ment. “They re­main at high risk of re­cur­ring heart at­tacks. By study­ing these high­est risk pa­tients, we were able to demon­strate re­duc­tions in MACE and a re­duc­tion in mor­tal­i­ty.”

While most of the at­ten­tion in the cho­les­terol mar­ket has cen­tered on the two PC­SK9 drugs, the two key com­pa­nies aren’t alone here. Es­pe­ri­on CEO Tim Mayleben has made it clear that they plan to charge un­der $4,000 for their late-stage cho­les­terol pill, now in late-stage de­vel­op­ment. That price point may not look like so much of a bar­gain now. And The Med­i­cines Com­pa­ny has been putting all their eggs in one RNAi bas­ket on LDL cho­les­terol as well, which may al­so face al­tered prospects.

This kind of pub­lic dis­cus­sion about re­tail drug prices is a re­mark­able change for an in­dus­try that has ben­e­fit­ed enor­mous­ly by keep­ing their true prices as opaque as pos­si­ble. But now da­ta aren’t enough, as pay­ers find new ways to put some dis­tance be­tween them­selves and the mass mar­ket drugs that threat­en to eat in­to their mar­gins.

Now you al­so have to pub­licly com­pete on the stick­er price, on oc­ca­sion.

Im­age: Sanofi CEO Olivi­er Brandi­court on Jan­u­ary 31, 2018  Alek­sey Nikol­skyi/Sput­nik via AP

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

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No­var­tis is eye­ing a multi­bil­lion-dol­lar Med­Co buy­out as Jer­sey biotech nears NDA — re­ports

To get from Novartis’ US headquarters to the Medicines Company, you make a left out of a square concrete building on NJ-Route 10, follow it past the sun orange veranda of Jersey’s Hot Bagels and the inexplicable green Vermont cabin that houses the Whippany Railway Museum until you turn right and immediately arrive at a rectangular glass building. It should take you about 12 minutes.

Reports are out that Novartis may be making that trip. Amid a torrent of Phase III data burnishing MedCo’s chances at a blockbuster cholesterol drug,  Bloomberg News is reporting that Novartis is looking to acquire the Jersey-based biotech.

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UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

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Badrul Chowdhury. FDA via Flickr

As­traZeneca los­es an­oth­er ex­ec­u­tive to biotech, as Badrul Chowd­hury moves to Savara

Another executive is migrating from the echelons of Big Pharma to the corridors of small biotech.

In April 2018, Badrul Chowdhury took his more than two decades of experience at the FDA to AstraZeneca, where he took on the role of senior vice president and chief physician-scientist for respiratory, inflammation and autoimmunity late-stage development in biopharmaceuticals R&D.

After about a year and a half in this role, Chowdhury is moving to a small Texas biotech called Savara, where he will serve as chief medical officer.

Yiannis Kiachopoulos and Artur Saudabayev, co-founders of Causaly

Lon­don AI up­start, which counts No­var­tis as a cus­tomer, can teach your com­put­er to read

When Amazon developed a machine-learning tool to make its recruitment process more efficient — the man-made system absorbed the gender-bias of its human makers, and the project was aborted. In the field of biopharmaceuticals, the way researchers train their machine learning algorithms can skew the outcome of predictions. But before those predictions can be made, the engine must learn to read to make sense of explosive volume of knowledge out there.

Burt Adelman. Novo Ventures

Here's a $25M seed fund aimed at back­ing some brash new drug ideas out of the Broad

As a former academic and a seasoned drug developer, Burt Adelman knew when he was recruited as a senior advisor to Novo Ventures in 2017 that one of his key priorities needs to be introducing the fund to the network he was so deeply embedded in.

“I was thinking long and hard on how can I, as a Boston insider, help Novo really get inside the ecosystem of Boston biotech?” he recalled in an interview with Endpoints News.

Welling­ton lines up a $393M bankroll for its next round of pri­vate biotech bets — and they’re like­ly think­ing big

Wellington Management made some uncustomary waves at the beginning of the year when it threw its considerable weight against Bristol-Myers Squibb’s $74 billion Celgene buyout. But after Bristol-Myers’ biggest investor conceded that game to the influential proxy firms involved, they’re now going to end the year by rolling out a big new investment fund for a new stable of fledgling biotechs on the private side of the industry.

As uter­ine race with Ab­b­Vie heats up, My­ovant eyes FDA ap­proval with tri­al re­sults from prostate can­cer

Myovant has long had a secret weapon in its uterine rivalry with AbbVie: Men.

While the small Swiss biotech has jockeyed with the Illinois-based giant for a foothold in the endometriosis and uterine fibroid therapy market, the company has been developing the same lead compound, relugolix, for use in one of the most common cancers for the uterus-less: prostate cancer. Today, Myovant is out with positive topline results from its big Phase III trial on the gonadotropin-releasing hormone (GnRH) antagonist. They say they’ve reached every primary and secondary endpoint with p values less than .0001.