UP­DAT­ED: J&J beats Tagris­so and Take­da to the punch in key NSCLC sub­set, pick­ing up new FDA ap­proval

Look­ing to out­flank As­traZeneca’s best-sell­ing drug in a non-small cell lung can­cer niche, J&J scored an im­por­tant ap­proval Fri­day af­ter­noon.

Reg­u­la­tors gave the thumbs-up to Janssen’s ami­van­tam­ab for the treat­ment of metasta­t­ic NSCLC with EGFR ex­on 20 in­ser­tion mu­ta­tions, the FDA an­nounced Fri­day. It’s the first drug ap­proved to treat such pa­tients, with J&J plant­i­ng a stake in a part of the EGFR mu­ta­tion are­na where its com­peti­tors have strug­gled to gain a foothold.

The drug, whose ap­proval comes af­ter J&J jumped straight from a Phase I study to a BLA pri­or­i­ty re­view, will be brand­ed as Ry­bre­vant. In an emailed state­ment to End­points News, J&J de­clined to com­ment on spe­cif­ic pric­ing for the drug, say­ing on­ly that it would “re­flect its in­cre­men­tal val­ue” in NSCLC out­comes for this pop­u­la­tion and be “com­pa­ra­ble to oth­er in­fused on­col­o­gy med­i­cines.”

While lung can­cer is the most com­mon form of can­cer and is the lead­ing cause of world­wide can­cer deaths, pa­tients with EGFR ex­on 20 in­ser­tion mu­ta­tions had been ex­clud­ed from tak­ing pre­vi­ous­ly ap­proved drugs — on­ly about 2% to 3% of NSCLC pa­tients have these mu­ta­tions, the FDA said. That list in­cludes As­traZeneca’s block­buster Tagris­so, which raked in more than $4 bil­lion last year.

Tagris­so is on­ly OK’ed for ex­on 19 dele­tions or ex­on 21 L858R mu­ta­tions, or pa­tients with EGFR mu­ta­tions who had un­der­gone tu­mor re­sec­tion and op­tion­al, stan­dard post­op­er­a­tive ad­ju­vant chemother­a­py.

One of the pri­ma­ry rea­sons past med­i­cines haven’t worked in this new class is the drugs don’t bind all that well to the tar­get, J&J in­ves­ti­ga­tor Joshua Sabari told End­points ahead of WCLC in Jan­u­ary. But Ry­bre­vant is an EGFR/MET bis­pe­cif­ic that binds out­side of the cell, which J&J says bet­ter in­hibits tu­mor growth among the ex­on 20 in­ser­tion mu­ta­tion pop­u­la­tion.

Fri­day’s ap­proval was based on those WCLC Phase I da­ta, look­ing at 81 pa­tients whose NSCLC had pro­gressed on or af­ter plat­inum chemo. With­in the study, 32 in­di­vid­u­als saw at least a par­tial re­sponse, good for an ORR of 39.5%. The re­spons­es were al­so shown to last with the drug prompt­ing a me­di­an du­ra­tion of 11.1 months, and 20 of the 32 pa­tients demon­strat­ed a re­sponse of at least six months.

J&J like­ly won’t be sat­is­fied with just this in­di­ca­tion giv­en the com­pe­ti­tion from Tagris­so and an­oth­er pro­gram from Take­da called mobo­cer­tinib.

Re­searchers are con­tin­u­ing to study how Ry­bre­vant can af­fect ad­vanced NSCLC pa­tients when used in com­bi­na­tion with an in-house TKI called laz­er­tinib, pit­ting this com­bo head-to-head with Tagris­so in a Phase III tri­al in pre­vi­ous­ly un­treat­ed pa­tients. There’s al­so an­oth­er tri­al for the Ry­bre­vant/laz­er­tinib duo in­volv­ing pa­tients who have tak­en both Tagris­so and chemother­a­py but still pro­gressed.

The Take­da can­di­date pre­sent­ed da­ta back in Jan­u­ary show­ing a sim­i­lar over­all re­sponse rate of 35%, but high rates of se­vere GI side ef­fects could tem­per ex­pec­ta­tions. Ear­li­er this week at AS­CO, how­ev­er, mobo­cer­tinib post­ed a me­di­an OS of 24 months at a 14-month fol­low-up.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 128,900+ biopharma pros reading Endpoints daily — and it's free.

‘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.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.