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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

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With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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Sanofi CFO Jean-Baptiste de Chatillon (L) and CEO Paul Hudson (Romuald Meigneux/Sipa via AP Images)

Sanofi sees downtick in flu sales as it preps for launch of RSV an­ti­body

Sanofi expects its RSV antibody jointly developed with AstraZeneca will be available next season, executive VP of vaccines Thomas Triomphe announced on the company’s quarterly call.

Beyfortus, also known as nirsevimab, was approved in the EU back in November and is currently under FDA review with an expected decision coming in the third quarter of this year. The news comes as the FDA plans to hold advisory committee meetings over the next couple months to review RSV vaccines from Pfizer and GSK.

Christophe Weber, Takeda CEO (Photographer: Shoko Takayasu/Bloomberg via Getty Images)

Take­da fo­cus­es on ‘di­verse’ pipeline prospects on heels of two ac­qui­si­tions

After a whopping $4 billion asset buy from Nimbus Therapeutics, along with a $400 million deal with Hutchmed for a colorectal cancer drug, Takeda executives touted pipeline optimism on its latest earnings call this week.

That’s because the TYK2 inhibitor for psoriasis Takeda is getting from Nimbus, along with the Hutchmed fruquintinib commercialization outside of China, are just two of what it reports are 10 late-stage development programs of promising candidates.

Regeneron CSO George Yancopoulos (L) and CEO Len Schleifer at a groundbreaking for its new Tarrytown, NY facility, June 2022 (Lev Radin/Pacific Press/LightRocket via Getty Images)

In show­down with Roche, Re­gen­eron gears up for po­ten­tial Eylea ex­pan­sion amid Covid de­cline

Regeneron faced a substantial slump in overall revenue last year, but the focus still remains on some of its biggest blockbusters.

The pharma with several high-profile partnerships — Sanofi and Bayer among them — said Friday that Q4 revenue was down 31% for the quarter, and down 24% for the entire year. However, that won’t stop blockbuster expansion plans.

One of those is Eylea, the Bayer-partnered eye disease drug that has been in major competition with Roche’s Vabysmo. While Eylea is currently only approved in a 2 mg dose, the company recently filed for approval to give a 8 mg dose, in hopes of making a longer-lasting treatment.