Ap­peals court sides with Bris­tol My­ers Squibb in years-long bat­tle with in­vestors over Op­di­vo fail

Bris­tol My­ers Squibb’s years-long court bat­tle with in­vestors over a failed Op­di­vo study is com­ing to a close. Sec­ond Cir­cuit judges sided with the phar­ma gi­ant on Fri­day, af­firm­ing a fed­er­al court’s de­ci­sion to dis­miss a case sur­round­ing a lung can­cer tri­al for the block­buster PD-1 check­point in­hibitor.

Op­di­vo, al­so known as nivolum­ab, won its first ap­proval back in 2014 for ad­vanced melanoma, and has since tacked on a lengthy list of can­cer in­di­ca­tions. But this par­tic­u­lar case traces back to a dis­ap­point­ing 2016 read­out in non-small cell lung can­cer, which shed rough­ly $20 bil­lion off the com­pa­ny’s mar­ket cap in pre-mar­ket trad­ing.

The drug works by pre­vent­ing the PD-L1/PD-1 in­ter­ac­tion in can­cer cells, ren­der­ing them vul­ner­a­ble to the body’s im­mune sys­tem. But not all can­cer cells have the PD-1 pro­tein — so the high­er a pa­tient’s PD-L1 ex­pres­sion, the more ef­fec­tive the drug. BMS re­vealed back in Au­gust 2016 that Op­di­vo did not meet the pri­ma­ry end­point in the Phase III Check­Mate-026 study, just months af­ter Mer­ck tout­ed a win in that same set­ting with its PD-1 ri­val Keytru­da.

How­ev­er, there was a key dif­fer­ence among the tri­als. While both claimed to en­roll pa­tients with “strong” PD-L1 ex­pres­sion, BMS set the thresh­old at 5%, while Mer­ck de­fined “strong” ex­pres­sion as high­er than 50%.

BMS’ fail­ure in NSCLC left in­vestors shak­ing their heads — and in 2018, sev­er­al filed suit against the phar­ma gi­ant al­leg­ing that it “mis­rep­re­sent­ed the study” by de­clin­ing to dis­close the 5% PD-L1 ex­pres­sion thresh­old in ad­vance.

“The claim in this suit is that 5% is not a ‘strong’ ex­pres­sion, and that the class was there­by mis­led to over­es­ti­mate the prospect of the tri­al’s suc­cess,” court doc­u­ments state.

A fed­er­al judge in New York dis­missed an amend­ed com­plaint in 2020 for fail­ure to state a claim, main­tain­ing that the in­vestors failed to “al­lege (i) ma­te­r­i­al mis­rep­re­sen­ta­tions or omis­sions or (ii) facts giv­ing rise to a strong in­fer­ence of sci­en­ter.”

Sec­ond Cir­cuit judge Den­nis Ja­cobs af­firmed that de­ci­sion in an opin­ion on Fri­day, con­clud­ing that there was no gen­er­al­ly un­der­stood mean­ing of “strong” ex­pres­sion at the time, and al­so that no ev­i­dence in­di­cates BMS had an oblig­a­tion to dis­close the pre­cise thresh­old.

In fact, BMS “cau­tioned the pub­lic” that it would not do so, Ja­cobs wrote.

De­spite Mer­ck’s de­f­i­n­i­tion of up to 49% ex­pres­sion as “weak,” Ja­cobs said “there was lit­tle con­sen­sus among in­dus­try par­tic­i­pants and re­searchers as to the ex­pres­sion lev­els con­sti­tut­ing ‘strong’ PD-L1 ex­pres­sion and PD-L1 ‘pos­i­tiv­i­ty.'”

With re­spect to PD-L1 pos­i­tiv­i­ty, the Ju­ly 2015 Jour­nal of Tho­racic On­col­o­gy sur­veyed the thresh­old used for “pos­i­tive” ex­pres­sion in var­i­ous stud­ies, not­ing that many used 5%, while some used 1% or 10%. The pub­li­ca­tion showed that in sev­er­al stud­ies, Mer­ck con­sid­ered any ex­pres­sion up to 49% “weak.” Sim­i­lar­ly, a May 26, 2016 med­ical pub­li­ca­tion stat­ed that “[t]he best cut-off per­cent­age of scored cells to de­ter­mine PD-L1 pos­i­tiv­i­ty … re­mains an un­re­solved ques­tion” but “the thresh­old most of­ten cho­sen is >5% ex­pres­sion.”

“Bris­tol My­ers Squibb is pleased with the unan­i­mous de­ci­sion of the ap­pel­late court to af­firm the dis­trict court’s dis­missal of this law­suit,” a spokesper­son told End­points News. 

Op­di­vo raked in more than $7.5 bil­lion last year, and snagged an ap­proval ear­li­er this month in com­bi­na­tion with chemother­a­py for adults with NSCLC in the neoad­ju­vant set­ting.

Mark Awad, clin­i­cal di­rec­tor of the Lowe Cen­ter for Tho­racic On­col­o­gy at the Dana-Far­ber Can­cer In­sti­tute and a study in­ves­ti­ga­tor, said in a state­ment that the ap­proval “marks a turn­ing point in how we treat re­sectable NSCLC.”

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; 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.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Tar­sus looks to raise aware­ness of eye­lid mite dis­ease in cam­paign aimed at eye­care spe­cial­ists

Eyelid mite disease may be “gross” but it’s also fairly common, affecting about 25 million people in the US.

Called demodex blepharitis, it’s a well-known condition among eyecare professionals, but they often don’t always realize how common it is. Tarsus Pharmaceuticals wants to change that with a new awareness campaign called “Look at the Lids.”

The campaign and website debut Thursday — just three weeks after Tarsus filed for FDA approval for a drug that treats the disease.

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