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.

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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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 with any issues.

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As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources.