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.”

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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UP­DAT­ED: CMS to re­strict cov­er­age of Bio­gen's con­tro­ver­sial Alzheimer's drug to on­ly clin­i­cal tri­als

The Centers for Medicare and Medicaid Services on Tuesday said it will only pay for Biogen’s Aduhelm and other FDA-approved anti-amyloid monoclonal antibodies for Alzheimer’s disease under CMS-approved randomized controlled trials.

The draft national coverage decision, which insurers nationwide are likely to follow, makes clear that CMS will be looking for randomized controlled trials that “demonstrate a clinically meaningful benefit in cognition and function.” That will be a tough task for Biogen, which previously showed conflicting benefits from past Aduhelm trials that were initially cut short due to futility and then resurrected for the accelerated approval.

CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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