Sanofi, Re­gen­eron bur­nish their block­buster Dupix­ent fran­chise with pos­i­tive re­sults in chil­dren with un­con­trolled eczema

As a sta­ble of new play­ers sets out to top­ple Dupix­ent’s sta­tus as the reign­ing an­ti­body treat­ment for atopic der­mati­tis, the block­buster’s de­vel­op­ers are mov­ing the goal­posts.

Dupix­ent has aced a Phase III tri­al in­volv­ing 162 chil­dren be­tween 6 months and 5 years old, Sanofi and Re­gen­eron say, be­com­ing the first bi­o­log­ic drug to show ef­fi­ca­cy in this young pop­u­la­tion. When giv­en Dupix­ent on top of stan­dard of care top­i­cal cor­ti­cos­teroids, 28% of pa­tients achieved clear or al­most-clear skin com­pared to 4% of those on place­bo — thus meet­ing the pri­ma­ry end­point.

Sanofi and Re­gen­eron have bet big on the Dupix­ent fran­chise, and an­a­lysts have large­ly ex­pect­ed it to pay off, with Jef­feries once peg­ging peak sales at $12.5 bil­lion.

Core to the pitch for physi­cians will be the fact that even as it clears eczema, the drug doesn’t broad­ly sup­press the im­mune sys­tem, which could be par­tic­u­lar­ly dan­ger­ous for young in­fants.

By bind­ing to IL-4Rα, the drug is de­signed to block sig­nal­ing of the IL-4 and IL-13 path­ways.

“When a child is di­ag­nosed with mod­er­ate-to-se­vere atopic der­mati­tis in the first few months of life, many as­pects of their child­hood can be sig­nif­i­cant­ly im­pact­ed. Par­ents and care­givers are chal­lenged to find safe and ef­fec­tive treat­ment op­tions,” said John Reed, Sanofi’s head of R&D. “Cur­rent­ly, the stan­dard of care for this pa­tient pop­u­la­tion is top­i­cal steroids and oth­er im­muno­sup­pres­sive med­i­cines may be used which can dam­age del­i­cate skin and, if used long-term, po­ten­tial­ly im­pact growth.”

The drug, which is al­ready ap­proved for chil­dren aged 6 or above, al­so met the co-pri­ma­ry end­point out­side of the US, which is 75% or greater over­all dis­ease im­prove­ment from base­line. In the drug arm, 53% hit that thresh­old, ver­sus 11% with place­bo, good for a p-val­ue of p<0.0001.

In­ves­ti­ga­tors al­so spelled out stel­lar num­bers on a hand­ful of sec­ondary end­points, in ad­di­tion to “sig­nif­i­cant­ly im­proved mea­sures” in symp­toms such as sleep, skin pain and oth­er qual­i­ty of life met­rics.

  • 70% av­er­age im­prove­ment from base­line in EASI com­pared to 20% im­prove­ment with place­bo (p<0.0001)
  • 49% av­er­age im­prove­ment from base­line in itch com­pared to 2% im­prove­ment in place­bo (p<0.0001)

Dur­ing the 16-week treat­ment pe­ri­od, the com­pa­nies added, pa­tients on Dupix­ent were 50% less like­ly to get a skin in­fec­tion — 12% of them had at least one in­fec­tion, com­pared to 24% on place­bo. Over­all, there were 11 in­fec­tions in the drug arm and 34 in­fec­tions in the place­bo arm.

Eli Lil­ly, Pfiz­er, Am­gen and oth­ers are hot in pur­suit of the drug as they seek a slice of the eczema mar­ket for them­selves. But they will first have to crash a sol­id wall of da­ta that Sanofi and Re­gen­eron con­tin­ue to build.

Ed­i­tor’s Note: This sto­ry has been up­dat­ed to clar­i­fy the re­sults on skin in­fec­tions.

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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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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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.