In a stun­ning set­back, FDA spurns Eli Lil­ly’s mar­ket­ing ap­pli­ca­tion for baric­i­tinib, de­mands more da­ta


The FDA has re­ject­ed Eli Lil­ly’s block­buster con­tender baric­i­tinib, say­ing that the phar­ma gi­ant will need to gath­er sig­nif­i­cant­ly more da­ta be­fore reg­u­la­tors will re­con­sid­er their de­ci­sion.

Ac­cord­ing to a state­ment from Lil­ly, the phar­ma gi­ant will not on­ly need to pro­vide more clin­i­cal da­ta on the ap­pro­pri­ate dos­es to be used for rheuma­toid arthri­tis, reg­u­la­tors are al­so de­mand­ing more safe­ty da­ta, which could sig­nif­i­cant­ly de­lay any re­sponse to the CRL. Lil­ly says it dis­agreed with the FDA’s con­clu­sion and the re­jec­tion.

The kick­back marks a stun­ning set­back for Eli Lil­ly $LLY CEO Dave Ricks, who owes in­vestors a string of promised ap­provals fol­low­ing a long drought in the clin­ic. The phar­ma gi­ant is known for its care­ful, if slow, ap­proach to late-stage de­vel­op­ment. Baric­i­tinib has been tagged as one of the top block­busters in late-stage de­vel­op­ment and an im­por­tant new drug for Lil­ly.

Hervé Hop­penot, In­cyte CEO

The re­jec­tion is al­so a set­back for its biotech part­ner, In­cyte $IN­CY, which li­censed out the drug to Lil­ly 8 years ago for $90 mil­lion up­front. An­a­lysts have pegged this as a po­ten­tial block­buster ca­pa­ble of earn­ing up to $2 bil­lion in peak an­nu­al sales, but that’s an­oth­er num­ber that is like­ly to get a se­ri­ous re­view.

Ever­cor­eISI’s Umer Raf­fat be­lieves this could in­di­cate that the FDA may ul­ti­mate­ly ap­prove a low dose of the drug, which could be­dev­il the de­vel­op­ers’ plans. He not­ed:

We’re wait­ing to hear back from com­pa­ny … but my sum­ma­ry thoughts are along the lines of:  there is a clear de­lay here, but I think they should get ap­proved ul­ti­mate­ly (keep in mind baric­i­tinib ap­proved in Eu­rope now).  How­ev­er, if FDA is re­al­ly fo­cused so much on “ap­pro­pri­ate dose”, I won­der if 2 mg is ul­ti­mate­ly the best dose … and if that’s the case, then it’s not so clear that 2 mg is su­pe­ri­or to Hu­mi­ra (re­call the head to head su­pe­ri­or­i­ty of baric­it­nib vs Hu­mi­ra was us­ing 4 mg dose … and plen­ty of da­ta from oth­er tri­als sug­gest­ing 2 mg has low­er ra­di­ograph­ic pro­gres­sion than 4 mg).

Lil­ly chose to re­lease the news on the morn­ing of Good Fri­day, a bank hol­i­day, de­lay­ing the beat­ing these two com­pa­nies faced. In­vestors, though, weren’t in a bet­ter mood Mon­day morn­ing. Lil­ly’s shares dropped 5.6% while In­cyte’s shares slid 13%.

Lil­ly’s John Lech­leit­er – now chair­man of the board – ini­tial­ly promised in­vestors at least two new drug ap­provals per year be­gin­ning in 2013, but had to de­lay on de­liv­er­ing un­til 2014. The com­pa­ny has al­so had three straight late-stage fail­ures for solanezum­ab in Alzheimer’s dis­ease. But new drugs have been kick­ing in, help­ing Lil­ly to start to grow its num­bers af­ter be­ing pum­meled by gener­ics for years.

I queried a com­pa­ny spokesper­son on whether Lil­ly now ex­pects to keep its promise on sev­er­al new drug ap­provals in 2017. She fol­lowed up by point­ing out that Lil­ly most re­cent­ly promised 20 new ap­provals be­tween 2014 and 2023, and that’s ev­i­dent­ly not re­strict­ed to FDA OKs. Baric­i­tinib al­so gets to count, as it was ap­proved in Eu­rope — as Olu­mi­ant — where it will be sub­ject­ed to a sin­gle-pay­er re­view and sig­nif­i­cant­ly low­er re­im­burse­ments.

That log­ic isn’t like­ly to help with dis­ap­point­ed an­a­lysts.

The re­jec­tion pro­vides Re­gen­eron and its part­ners at Sanofi a chance to over­come its re­cent re­jec­tion on sar­ilum­ab — for man­u­fac­tur­ing rea­sons — and push ahead with a ri­val ther­a­py that many an­a­lysts be­lieve is the odds-on fa­vorite. It al­so marks an­oth­er ad­van­tage for Ab­b­Vie, which has been cir­cling the wag­ons around Hu­mi­ra as it mounts a de­fense against new ther­a­pies bit­ing off pieces of its multi­bil­lion dol­lar fran­chise ther­a­py.

A new re­port from ICER took is­sue with the price for Hu­mi­ra, which it post­ed as a net of $40,415 a year. And ICER pro­vid­ed a thumbs up for baric­i­tinib and sar­ilum­ab. ICER clear­ly prefers sar­ilum­ab on ef­fi­ca­cy — though we don’t know the price — giv­ing on­ly a mar­gin­al stamp of ap­proval to baric­i­tinib.


“We are dis­ap­point­ed with this ac­tion. We re­main con­fi­dent in the ben­e­fit/risk of baric­i­tinib as a new treat­ment op­tion for adults with mod­er­ate-to-se­vere RA,” said Christi Shaw, pres­i­dent of Lil­ly Bio-Med­i­cines. “We will con­tin­ue to work with the FDA to de­ter­mine a path for­ward and ul­ti­mate­ly bring baric­i­tinib to pa­tients in the U.S.”

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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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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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.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

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.

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.

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.