Up­dat­ed: Cel­gene, Agios win a land­mark FDA OK for new AML drug Id­hi­fa

David Schenkein, Agios CEO

Cel­gene and Agios didn’t have to wait un­til the PDU­FA date at the end of Au­gust to get a speedy FDA de­ci­sion on enasi­denib (AG-221), their new ther­a­py for acute myeloid leukemia. The FDA cut to the chase and ap­proved it to­day.

Cel­gene $CELG re­worked its deal with Agios $AGIO last year, but kept its hands on its rights to AG-221 in pa­tients with ad­vanced hema­to­log­ic ma­lig­nan­cies with an IDH2 mu­ta­tion. In turn, Agios stayed ra­zor fo­cused on grab­bing the ear­li­est pos­si­ble ap­proval, hus­tling Phase I/II da­ta straight to reg­u­la­tors for an ac­cel­er­at­ed re­view.

The drug will now be sold as Id­hi­fa, con­cen­trat­ing on about 9% to 13% of the AML mar­ket.

“The use of Id­hi­fa was as­so­ci­at­ed with a com­plete re­mis­sion in some pa­tients and a re­duc­tion in the need for both red cell and platelet trans­fu­sions,” not­ed the FDA’s Richard Paz­dur in herald­ing the OK to­day. The drug will be used with the Re­al­Time IDH2 As­say, which is used to de­tect spe­cif­ic mu­ta­tions in the IDH2 gene in pa­tients with AML.

It won’t come cheap. From Cel­gene:

The ap­proval of ID­HI­FA rep­re­sents a new, tar­get­ed ther­a­py for a sub­type of AML with an ex­treme­ly rare ge­net­ic mu­ta­tion. The 8-19% of AML pa­tients that have an IDH2 mu­ta­tion rep­re­sent about 1,200 to 1,500 in­di­vid­u­als in the U.S. These pa­tients are liv­ing with dis­ease that has a poor prog­no­sis and no stan­dard of care and no oth­er cur­rent­ly ap­proved op­tions un­til to­day. Pair­ing this ther­a­py with an ap­proved com­pan­ion di­ag­nos­tic al­so sig­nif­i­cant­ly im­proves iden­ti­fi­ca­tion of el­i­gi­ble pa­tients who could ben­e­fit from this new­ly ap­proved treat­ment.

The month­ly whole­sale ac­qui­si­tion cost of ID­HI­FA is $24,872. In the piv­otal study, the me­di­an time on ther­a­py for pa­tients was 4.3 months

Cel­gene first al­lied it­self with Agios back in 2010, part­ner­ing on its work in can­cer me­tab­o­lism. That deal led Cel­gene to grab world­wide rights to AG-221 in 2014. Cel­gene hand­ed back rights to AG-120, an IDH1 in­hibitor, but al­so an­ted up an­oth­er $200 mil­lion to grab op­tions on a slate of ex­per­i­men­tal drugs in the biotech’s pipeline.

The re­la­tion­ship paid off nice­ly for Cel­gene. The jour­ney from first-in-hu­man test­ing to a reg­u­la­to­ry fil­ing took just three years, an in­cred­i­bly fast speed in R&D. And Agios plans to do that again with oth­er drugs in its pipeline. Leerink’s says it’s a big step for both com­pa­nies, which will be fol­lowed close­ly dur­ing the mar­ket launch.

This is the first drug to emerge from Cel­gene’s col­lab­o­ra­tion with Agios, and from Agios’ re­search plat­form in can­cer me­tab­o­lism, and al­so the first drug to be ap­proved from Cel­gene’s net­worked re­search arrange­ments. It pro­vides im­por­tant val­i­da­tion for both plat­form and strat­e­gy, and in­vestors will close­ly mon­i­tor the drug’s com­mer­cial per­for­mance to as­sess how well these ad­vances trans­late in­to com­mer­cial suc­cess. Cel­gene is the pri­ma­ry com­mer­cial­iz­ing par­ty in the US, al­though Agios has opt­ed in to co-com­mer­cial­ize the prod­uct in the US. Cel­gene has sug­gest­ed that they will add ap­prox­i­mate­ly 30 head­count to sup­port the prod­uct’s com­mer­cial­iza­tion on the US. Cel­gene es­ti­mates that there is a tar­get­ed pa­tient pop­u­la­tion of 1,200-1,500 pa­tients in the US and ex­pects the du­ra­tion of treat­ment to ap­prox­i­mate the 4 months ob­served in the phase I/II tri­al.

Leerink’s Michael Schmidt al­so took a step back and sized up the im­pli­ca­tions for the biotech, now that it owns the IDH1 ther­a­py. It all adds up to a siz­able op­por­tu­ni­ty, he notes:

In our view, FDA-ap­proval of Id­hi­fa al­so re­duces reg­u­la­to­ry risk for ivosi­denib in AML, the lat­ter be­ing pro­pri­etary to AGIO and hence rep­re­sent­ing a more sig­nif­i­cant val­ue dri­ver for the com­pa­ny. AGIO’s IDH1 & 2 in­hibitors ad­dress a ~$270M and ~$370M glob­al mar­ket op­por­tu­ni­ty in re­lapsed/re­frac­to­ry AML, re­spec­tive­ly, based on our up­dat­ed es­ti­mates; po­ten­tial front-line use in com­bi­na­tion with ap­proved or in­ves­ti­ga­tion­al agents re­flects a sig­nif­i­cant­ly larg­er $1Bn+ com­mer­cial op­por­tu­ni­ty based on our re­cent due dili­gence should on­go­ing and planned front-line clin­i­cal tri­als suc­ceed.

CEO David Schenkein is fond of re­call­ing Agios start­ed out with lit­tle more than a blank sheet of pa­per. Since then, the pages have been filled with high-pro­file part­ner­ships, an IPO for its po­ten­tial cut­ting-edge work and now its first new drug ap­proval. It’s a wa­ter­shed mo­ment for this biotech.


How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

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No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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In­cyte’s PD-(L)1 in­hibitor head­ed for an ODAC show­down next month

The FDA’s Oncologic Drugs Advisory Committee will spend a half day on June 24 reviewing Incyte’s PD-(L)1 inhibitor retifanlimab as a treatment for locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) for those who have progressed on or who are intolerant of platinum-based chemotherapy.

The eighth PD-(L)1 entrant in January nabbed a priority review and an orphan designation from the FDA, which sets the agency’s final decision date as July 25.