Bris­tol-My­ers craters af­ter block­buster check­point drug Op­di­vo fails key lung can­cer study

Bris­tol-My­ers Squibb an­nounced this morn­ing that Op­di­vo has flopped in a late-stage study on non-small cell lung can­cer, pre­sent­ing a stun­ning set­back for the star ther­a­py. Its shares $BMY im­me­di­ate­ly plunged 18%, wip­ing out bil­lions in mar­ket val­ue, while ri­val Mer­ck $MRK—a run­ner-up in the check­point mar­ket—saw its shares soar 10%.

Re­searchers had re­cruit­ed a broad pop­u­la­tion of 541 pre­vi­ous­ly un­treat­ed first line pa­tients whose tu­mors ex­pressed PD-L1 at ≥ 5%, a key bio­mark­er used to iden­ti­fy pa­tients most like­ly to re­spond. The Op­di­vo arm was com­pared to a group who re­ceived their physi­cian’s choice of al­ter­na­tive ther­a­pies. But this time, in the first ma­jor re­ver­sal for Bris­tol-My­ers, the drug failed to de­liv­er a sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival.

The fo­cus now may cen­ter on the lev­el of PD-L1 ex­pres­sion used to qual­i­fy pa­tients. Last fall, when the FDA ex­pand­ed its ap­proval of Op­di­vo to NSCLC pa­tients whose can­cer had spread af­ter chemo, FDA can­cer czar Richard Paz­dur not­ed:

“While Op­di­vo showed an over­all sur­vival ben­e­fit in cer­tain non-small cell lung can­cer pa­tients, it ap­pears that high­er ex­pres­sion of PD-L1 in a pa­tient’s tu­mor pre­dicts those most like­ly to ben­e­fit.”

“The missed re­sult like­ly re­flects the fact that BMY pushed the en­ve­lope too far in de­sign­ing its tri­al,” not­ed Bern­stein’s Tim An­der­son. “Specif­i­cal­ly, as men­tioned in the press re­lease to­day, they chose a “cut-off val­ue” for PDL1 ex­pres­sion of 5%.  This is in-line with what we had been say­ing (that 5% was the val­ue), where­as the con­sen­sus view had been that the cut-off was 10%.  By mak­ing it 5%, BMY was in essence try­ing to broad­en the pa­tient pop­u­la­tion where it could claim a ben­e­fit (had re­sults been pos­i­tive, of course), but failed re­sults sug­gest they like­ly made it too broad, mean­ing they en­rolled pa­tients with too lit­tle PDL1 ex­pres­sion, and this soured the over­all analy­sis.  The pop­u­la­tion MRK stud­ied was nar­row­er.”

I/O in­vest­ment spe­cial­ist Brad Lon­car had this to say:

Bris­tol’s more ag­gres­sive strat­e­gy of fo­cus­ing on a broad­er pop­u­la­tion rather than high PD-L1 ex­pres­sors has worked out for them in lat­er stages of dis­ease, but it looks like that has fi­nal­ly reached its lim­it. This is a very dis­ap­point­ing re­sult, but I think they de­serve cred­it for try­ing to help as many pa­tients as pos­si­ble.

Mer­ck has been lag­ging far be­hind Bris­tol-My­ers Squibb in the check­point sales race, with

Gio­van­ni Caforio, Bris­tol-My­ers Squibb CEO

Op­di­vo OK’d for use with­out a di­ag­nos­tic test while Keytru­da pa­tients have to be screened. Free of test­ing pa­tients, Op­di­vo has raced far ahead on the sales front. But Keytru­da—which was test­ed in pa­tients with a PD-L1 ex­pres­sion of 50%—looks to have the edge now in a key mar­ket­place.

These two pi­o­neer­ing drugs work es­sen­tial­ly the same way. They both dis­man­tle a hur­dle that can­cer cells re­ly on to es­cape an at­tack by the im­mune sys­tem. That has proven to be a game-chang­er in many types of can­cer, where new com­bi­na­tions are now be­ing test­ed to pro­vide a one-two punch against can­cer cells.

Gio­van­ni Caforio, the CEO at Bris­tol, had this to say:

While we are dis­ap­point­ed Check­Mate -026 did not meet its pri­ma­ry end­point in this broad pa­tient pop­u­la­tion, we re­main com­mit­ted to im­prov­ing pa­tient out­comes through our com­pre­hen­sive de­vel­op­ment pro­gram, in­clud­ing the on­go­ing Phase 3 Check­Mate -227 study ex­plor­ing the po­ten­tial of the com­bi­na­tion of Op­di­vo plusYer­voy for PD-L1 pos­i­tive pa­tients, and Op­di­vo plus Yer­voy, or Op­di­vo plus chemother­a­py in PD-L1 neg­a­tive pa­tients.


via Brad Lon­car

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

Big week for Alzheimer’s da­ta; As­traZeneca buys cell ther­a­py start­up; Dig­i­tal ther­a­peu­tics hits a pay­er wall; and more

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Am­gen, years be­hind ri­vals, says PhI obe­si­ty drug shows dura­bil­i­ty signs

While NBC ran “The Biggest Loser” for 17 seasons, deemed toxic by critics for the reality show’s punishing exercise and diet upheavals, researchers in pharmaceutical labs have been attempting to create prescription drugs that induce weight loss — and one pharma betting it can require less frequent dosing is out with a new crop of data.

Amgen was relatively late to the game compared to its approved competitor Novo Nordisk and green light-approaching rival Eli Lilly. But early data suggested Amgen’s AMG 133 led to a 14.5% weight reduction in the first few months of dosing, buoying shares earlier this fall, and now the California pharma is out with its first batch of durability data showing that figure fell slightly to 11.2% about 150 days after the last dose. Amgen presented at the 20th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease on Saturday afternoon.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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US month­ly costs for biosim­i­lars 'sub­stan­tial­ly high­er' than Ger­many or Switzer­land, JA­MA re­search finds

As the global biologics market is expected to hit nearly the half-trillion-dollar mark this year, new JAMA research points to the importance of timely biosimilar entry, particularly as fewer biosimilars are entering the US than in Europe, and as monthly treatment costs for biosimilars were “substantially higher” in the US compared with Germany and Switzerland.

Among the three countries, biosimilar market share at launch was highest in Germany, but increased at the fastest rate in the US, the authors from the University of Zurich’s Institute of Law wrote in JAMA Network Open today.

Kirk Myers is shown in a still image from a new film series showcasing the efforts of HIV advocates funded by Gilead.

Gilead spot­lights HIV projects and the com­mu­ni­ty lead­ers dri­ving them in new mi­ni-doc­u­men­tary films

Gilead is going behind the scenes of some of the HIV initiatives it funds through grants in a new film series narrated by the people helming the projects.

The first four films and leaders come from across the US — Arianna Lint in Florida and Puerto Rico, Cleve Jones in San Francisco, June Gipson in Mississippi and Kirk Myers in Texas. Their HIV-focused efforts range from addressing unmet needs of the transgender community to delivering social services and high-quality health care in underserved communities.

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EMA pulls an opi­oid from the 1950s used to treat dry cough

The European Medicines Agency said Friday that it’s pulling from all European markets pholcodine-containing medicines, which are an opioid used in adults and children for the treatment of dry cough and in combo with other drugs as a treatment for cold and flu.

The decision to pull the medicines comes as the EMA points to the results from the recent ALPHO study, which show that use of pholcodine during the 12 months preceding anesthesia is linked to a risk of an anaphylactic reaction related to the neuromuscular blocking agents (NMBAs) used (with an adjusted OR of 4.2, and a 95% confidence interval of 2.5 to 6.9).

David Arthur, Salarius Pharmaceuticals CEO

Salarius Phar­ma­ceu­ti­cals sees with­drawals, 3 of 13 pa­tient re­spon­ders in sar­co­ma tri­al

The Houston-based biotech Salarius Pharmaceuticals is lifting the cover on data from a Phase I/II trial for a drug currently on voluntary hold after a patient death, and the results appear to have underwhelmed investors.

Salarius’ candidate, dubbed seclidemstat, is an oral LSD1 inhibitor that is meant to treat Ewing sarcoma and FET-rearranged sarcomas in patients under 12 years old. The biotech had presented data with 13 patients with “first- and second-relapse Ewing sarcoma” who were treated in combination with topotecan and cyclophosphamide.