No­var­tis to pay near­ly $178M in law­suit over BRAF drug — and will be on the hook for roy­al­ty

Af­ter a four-year bat­tle over a can­cer drug patent, No­var­tis has been or­dered by a Cal­i­for­nia judge to pay a Dai­ichi Sankyo sub­sidiary $177.8 mil­lion.

Plexxikon filed a law­suit against the phar­ma gi­ant in 2017, alledg­ing that Tafin­lar, a ri­val to its melanoma drug Zelb­o­raf that was brought to mar­ket in col­lab­o­ra­tion with Roche, has stepped on its in­tel­lec­tu­al prop­er­ty. The ju­ry ruled in its fa­vor, adding that the in­fringe­ment is in fact will­ful.

On top of get­ting com­pen­sat­ed for the past in­fringe­ments, Plexxikon says it will re­ceive “ad­di­tion­al roy­al­ty pay­ments for fu­ture sales of Tafin­lar in the Unit­ed States through the life of the patents.”

Sales for Tafin­lar and Mekin­ist, the MEK in­hibitor it was ap­proved with, hit $672 mil­lion in 2016. Fast for­ward to 2020 and the duo gen­er­at­ed $1.5 bil­lion in rev­enue. In 2021, the com­bo has raked in $818 mil­lion in the first half of the year alone for No­var­tis, a num­ber that is al­ready up 11% from last year. Com­par­a­tive­ly, Roche re­port­ed $218 mil­lion in sales of Zelb­o­raf in 2016, and rev­enue was not re­port­ed in its most re­cent mid-year up­date.

The Plexxikon patents are for com­pounds that re­duce can­cer cell growth by block­ing V600E mu­tat­ed BRAF. Patents were filed as ear­ly as 2005.

No­var­tis and GSK car­ried out a swap of its vac­cine and can­cer drugs back in 2015. GSK paid $5.25 bil­lion to No­var­tis for its vac­cine busi­ness, and No­var­tis sent $16 bil­lion for GSK’s on­col­o­gy pro­grams. Tafin­lar and Mekin­ist had al­ready been grant­ed FDA ap­proval at the time of that deal, and as a part of that deal, No­var­tis agreed to di­vest its own BRAF and MEK in­hibitors to avoid cre­at­ing a mo­nop­oly.

Ac­cord­ing to Plexxikon, GSK sci­en­tists were on­ly able to make Tafin­lar af­ter talks with Plexxikon about a po­ten­tial part­ner­ship; al­though those talks nev­er turned in­to a li­cens­ing deal, GSK ap­par­ent­ly chan­neled that in­for­ma­tion and cre­at­ed a ri­val drug.

The suit says that while BRAF ki­nase in­hibitors ex­ist­ed pri­or to Plexxikon’s dis­cov­er­ies, they were not se­lec­tive, and Plexxikon’s have a core mol­e­c­u­lar struc­ture that al­lows them to bind se­lec­tive­ly to ki­nase cre­at­ed by the BRAF mu­ta­tion. That al­lows for high­er dos­es to be ad­min­is­tered.

“The ju­ry was care­ful and award­ed us what we’d asked for down to the pen­ny,” Plexxikon’s lawyer Dar­a­lyn Durie told Bloomberg af­ter the ver­dict came down.

The ju­ry unan­i­mous­ly ruled in Plexxikon’s fa­vor on all sev­en ques­tions, in­clud­ing that No­var­tis has not proved the spec­i­fi­ca­tion of the patent was full and clear enough to en­able a per­son of “or­di­nary skill” to make and use the in­ven­tion.

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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