Pfiz­er en­ters Al­ny­lam, Ion­is' TTR turf with ear­ly ap­proval for car­diomy­opa­thy drug, car­ry­ing a $225K price tag

Pfiz­er is set to pull its weight in transthyretin-me­di­at­ed amy­loi­do­sis, a field that has so far been Al­ny­lam and Io­n­is’ turf.

Transthyretin (TTR) is a rel­a­tive­ly abun­dant pro­tein in the blood, which trans­ports thy­rox­ine and retinol. But it can be­come un­sta­ble and mis­fold — due to a ge­net­ic mu­ta­tion or en­vi­ron­men­tal fac­tors —  spark­ing an ac­cu­mu­la­tion of tox­ic amy­loid ag­gre­gates in the heart or pe­riph­er­al nerves.

On Mon­day, the big US drug­mak­er $PFE said the FDA had ap­proved two oral for­mu­la­tions of its transthyretin-sta­bi­liz­er tafamidis — Vyn­daqel (80 mg, tak­en as four 20mg cap­sules) and Vyn­damax (61 mg, tak­en as a once-dai­ly sin­gle cap­sule) — to treat car­diomy­opa­thy of wild-type or hered­i­tary transthyretin-me­di­at­ed amy­loi­do­sis (AT­TR-CM) in adults, to re­duce re­lat­ed hos­pi­tal­iza­tion and death.

The drug has been tout­ed by Pfiz­er ex­ec­u­tives as a po­ten­tial block­buster. Last year, the com­pa­ny fol­lowed up pos­i­tive top-line re­sults with da­ta that in­di­cat­ed tafamidis spurred a 30% drop in mor­tal­i­ty risk along with a 32% re­duc­tion in the risk of CV-re­lat­ed hos­pi­tal­iza­tion.

Cred­it Su­isse’s Vamil Di­van es­ti­mat­ed peak sales of $2 bil­lion for tafamidis, but sees the “po­ten­tial for the prod­uct to be sig­nif­i­cant­ly larg­er than that if Pfiz­er is able to com­mer­cial­ize it suc­cess­ful­ly.”

Vyn­daqel com­pris­es of tafamidis meg­lu­mine, while Vyn­damax is made from tafamidis free acid — “both these dos­es are bioe­quiv­a­lent (in fact, the la­bel specif­i­cal­ly men­tions that every 20 mg of tafamidis meg­lu­mine is equiv­a­lent to 12.2 mg of tafamidis free acid),” Ever­core ISI’s Umer Raf­fat wrote in a note. Price has been set at $225,000/year, he not­ed.

How­ev­er, Phase III da­ta has shown sim­i­lar ef­fi­ca­cy at 20 mg and 80 mg, so a pa­tient should be the­o­ret­i­cal­ly able to take the small­er dose (with a $55,000 price tag) ef­fec­tive­ly — but, “it is my un­der­stand­ing that Pfiz­er will phase out the 80 mg (which is 4 pills of 20 mg) lat­er in the year. This will pre­vent this from hap­pen­ing,” he added.   

RNAi drug­mak­er Al­ny­lam $AL­NY makes On­pat­tro, which is de­signed to treat the polyneu­ropa­thy caused by hered­i­tary transthyretin-me­di­at­ed amy­loi­do­sis (hAT­TR amy­loi­do­sis). Io­n­is’ $IONS/Akcea’s $AK­CA Tegse­di is ap­proved for the same pa­tient pop­u­la­tion. Each treat­ment costs about $450,000 a year.

An­a­lysts have sug­gest­ed that even though the Pfiz­er drug and two ex­ist­ing prod­ucts are tar­get­ing dif­fer­ent in­di­ca­tions — there will still be com­pe­ti­tion — since many pa­tients with car­diomy­opa­thy tend to al­so have polyneu­ropa­thy and vice ver­sa.

The ear­li­er-than-ex­pect­ed ap­proval specif­i­cal­ly calls out be­ing able to re­duce mor­tal­i­ty and CV-re­lat­ed hos­pi­tal­iza­tions, mak­ing it like­ly tafamidis will own the seg­ment of the hAT­TR mar­ket that’s de­fined by pure car­diomy­opa­thy, Stifel an­a­lysts wrote in a note.

The mixed polyneu­ropa­thy/car­diomy­opa­thy pa­tients are more like­ly to be a bat­tle ground area where one can cer­tain­ly make a case for both tafamidis and knock­down drugs at the same time…But among pa­tients with true de­bil­i­tat­ing polyneu­ropa­thy, we ex­pect On­pat­tro/Tegse­di to be pre­ferred over tafamidis where for the lat­ter, the polyneu­ropa­thy da­ta are fair­ly equiv­o­cal/mod­est in our view. In the near to mid-term, we as­sume knock­down drugs can cap­ture 35% of mixed phe­no­type in 2021. We al­so be­lieve the pre­mi­um price of Tafamidis at over $225k is a mar­gin­al pos­i­tive for AL­NY/AK­CA/IONS; while you nev­er know for sure what pay­ors might do to re­strict ac­cess, if Tafamidis had been priced at a much low­er lev­el, say be­low $100k, it could’ve raised con­cerns that in­sur­ers would po­si­tion this drug as first line in hAT­TR across the board, re­gard­less of phe­no­type.

The big hur­dle in front of Pfiz­er is now get­ting AT­TR-CM di­ag­nosed prop­er­ly — rough­ly 100,000 Amer­i­cans suf­fer from the dis­ease, but on­ly 1% to 2% have been di­ag­nosed, ac­cord­ing to the drug­mak­er. Of­ten AT­TR-CM is di­ag­nosed on­ly af­ter symp­toms have be­come se­vere, and once di­ag­nosed, the me­di­an life ex­pectan­cy in pa­tients — de­pend­ing on the sub-type — is ap­prox­i­mate­ly 2 to 3.5 years, the com­pa­ny added.

“Pfiz­er has high­light­ed this is a mar­ket that will need to be build out…we un­der­stand that ~400-450 pa­tients are al­ready in the ex­pand­ed ac­cess pro­gram.  This like­ly means that 2020 con­sen­sus of $250 mil­lion is like­ly achiev­able,” Raf­fat not­ed.

Vyn­daqel has been ap­proved for transthyretin amy­loid polyneu­ropa­thy in the Eu­ro­pean Union since 2011, and is now ap­proved for the in­di­ca­tion in 40 coun­tries, ex­clud­ing the US where it was re­ject­ed for the in­di­ca­tion in 2012.

Bridge­bio-backed Ei­dos Ther­a­peu­tics $EI­DX is al­so de­vel­op­ing an oral treat­ment for TTR amy­loi­do­sis.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.

Ted Love. HAVERFORD COLLEGE

Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.


Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.


Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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J&J gains an en­thu­si­as­tic en­dorse­ment from Pres­i­dent Don­ald Trump for their big new drug Spra­va­to

Pres­i­dent Don­ald Trump has lit­tle love for Big Phar­ma, but there’s at least one new drug that just hit the mar­ket which he is en­am­ored with.

Trump, ev­i­dent­ly, has been read­ing up on J&J’s new an­ti-de­pres­sion drug, Spra­va­to. And the pres­i­dent — who of­ten likes to break out in­to a full-throat­ed at­tack on greedy drug­mak­ers — ap­par­ent­ly en­thused about the ther­a­py in a meet­ing with of­fi­cials of Vet­er­ans Af­fairs, which has long grap­pled with de­pres­sion among vet­er­ans.

Savara shares are crushed as PhI­II tri­al flunks pri­ma­ry, key sec­on­daries — but they can’t stop be­liev­ing

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

As an­oth­er an­tibi­otics biotech sinks in­to a cri­sis, warn­ings of a sec­tor ‘col­lapse’

Another antibiotics company is scrambling to survive today, forcing the company’s founding CEO to exit in a reorganization that eliminates its research capabilities as the survivors look to improve on minuscule sales of their newly approved treatment. And the news — on top of an alarming series of failures — spurred at least one figure in the field to warn of a looming collapse of the antimicrobial resistance research field.

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In a boost to Rit­ux­an fran­chise, Roche nabs quick ap­proval for po­latuzum­ab ve­dotin

Roche’s lat­est an­ti­body-drug con­ju­gate has crossed the FDA fin­ish line, gain­ing an ac­cel­er­at­ed ap­proval a full two months ahead of sched­ule.

Po­livy, or po­latuzum­ab ve­dotin, is a first-in-class drug tar­get­ing CD79b — a pro­tein promi­nent in B-cell non-Hodgkin lym­phoma. It will now be mar­ket­ed for dif­fuse large B-cell lym­phoma as part of a reg­i­men that al­so in­cludes the chemother­a­py ben­damus­tine and a ver­sion of rit­ux­imab (Rit­ux­an).