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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

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Jean-Jacques Bienaimé, BioMarin chairman and CEO

Bio­Marin holds the line on bleeds with 4-year val­rox up­date on he­mo­phil­ia A — but what's this about an­oth­er de­cline in Fac­tor 8 lev­els?

BioMarin has posted some top-line results for their 4-year followup on the most advanced gene therapy for hemophilia A — extending its streak on keeping a handful of patients free of bleeds and off Factor VIII therapy, but likely stirring fresh worries over a continued drop in Factor VIII levels.

We just don’t know how big a drop.

We’ll see more data when the results are presented at the World Federation of Hemophilia in a couple of weeks. But in a statement out Sunday night, BioMarin $BMRN reported that none of the patients required Factor VIII treatment, adding:

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As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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Iterum's fu­ture looks un­cer­tain, af­ter lead an­tibi­ot­ic fails con­sec­u­tive piv­otal stud­ies

While the market for antibiotics remains in tatters — unlike many of its bankrupt (or at the brink of bankruptcy) peers — Iterum is suffering not because its antibiotic isn’t selling, but because the compound has now failed back-to-back late-stage studies.

The experimental drug, sulopenem, was designed to tackle drug-resistant infections with an outpatient focus (in addition to hospitals), to avert those reimbursement challenges that incentivize hospitals to prescribe cheaper, generic broad-spectrum antibiotics.

Covid-19 roundup: Did in­sid­ers cash in on pos­i­tive news re­port about Gilead be­fore pub­li­ca­tion?

A series of bullish trades on Gilead options just before the release of a favorable news story is raising questions among regulatory experts, Reuters reported.

On April 16, just hours before STAT published anecdotes from a Chicago hospital that served as one of the clinical sites to test Gilead’s remdesivir in Covid-19 patients, the California-based company’s shares were trading at around $75. Four large blocks of options were purchased for about $1.5 million each, betting that the stock would rise beyond that to as much as $87.5 by mid-August.

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