Roche/Ex­elix­is' Cotel­lic fiz­zles in piv­otal melanoma study

To lit­tle sur­prise, Ex­elix­is’ Cotel­lic — known chem­i­cal­ly as co­bime­tinib — in com­bi­na­tion with Roche’s Tecen­triq, has failed a late-stage study as a front­line treat­ment for pa­tients with a form of ad­vanced melanoma.

The Alame­da, Cal­i­for­nia-based com­pa­ny’s $EX­EL ki­nase in­hibitor — out-li­censed to Roche — was ap­proved in 2015 in com­bi­na­tion with the Swiss drug­mak­er’s Zelb­o­raf (ve­mu­rafenib) for pa­tients with BRAF V600E or V600K mu­ta­tion-pos­i­tive un­re­sectable or metasta­t­ic melanoma. Cotel­lic gen­er­at­ed rough­ly $61 mil­lion in glob­al sales last year.

Re­sults of the IM­spire170 study were dis­closed in a fil­ing on Thurs­day. Ex­elix­is said that Genen­tech (Roche), which spon­sored the study, had found that co­bime­tinib + Tecen­triq (ate­zolizum­ab) did not re­duce the risk of dis­ease pro­gres­sion or death com­pared to stan­dard-of-care Keytru­da, Mer­ck’s flag­ship PD-1 im­munother­a­py, in treat­ment-naïve pa­tients with BRAF V600 wild-type ad­vanced melanoma.

Last year, in the Phase III IM­blaze370 study, co­bime­tinib + Roche’s PD-L1 Tecen­triq failed to sig­nif­i­cant­ly help pa­tients with col­orec­tal can­cer live longer.

The like­li­hood of co­bime­tinib en­hanc­ing the im­pact of check­point in­hibitor ther­a­py in this melanoma tu­mor type (and oth­ers) was great­ly di­min­ished fol­low­ing last year’s dis­clo­sure of IM­blaze370 da­ta, Stifel’s Stephen Wil­ley wrote in a note. “We don’t view this news as the­sis-chang­ing (i.e. co­bime­tinib is not part of our, or any­one’s, near- or longer-term EX­EL the­sis) and con­tin­ue to view the dis­place­ment of 1L im­munother­a­py in this set­ting as un­like­ly.”

BMO Cap­i­tal Mar­ket’s George Farmer said the da­ta were in­con­se­quen­tial to his over­all Ex­elix­is in­vest­ment the­sis. “Phase 3 suc­cess (in the IM­spire170 study) would on­ly pro­vide up­side to ex­ist­ing co­bi sales, which was not fac­tored in­to our mod­el.”

An­oth­er co­bime­tinib late-stage tri­al, called IM­spire150 TRIL­O­GY, is ex­pect­ed to read out be­fore the end of this year. The study is eval­u­at­ing a triplet com­bi­na­tion of ve­mu­rafenib/co­bime­tinib/ate­zolizum­ab ver­sus the dou­blet com­bi­na­tion of ve­mu­rafenib/co­bime­tinib in pa­tients with first­line BRAF mu­tant ad­vanced melanoma. “(T)his triplet vs. dou­blet tri­al as more of a ‘check the box’ vs. an ‘ex­pand the mar­ket’ ex­er­cise and, like IM­spire170, don’t view IM­spire150 topline re­sults as a key cat­a­lyst for the stock,” Wil­ley wrote.

“We al­so be­lieve the on­go­ing eval­u­a­tion of oth­er triple-ther­a­py com­bi­na­tions (BRAF/MEK/PD-1) in 1L BRAF-mu­tant melanoma by oth­er, more-en­trenched com­peti­tors would like­ly keep any en­thu­si­asm re­lat­ed to a po­ten­tial TRIL­O­GY win ap­pro­pri­ate­ly mut­ed.”

Ex­elix­is’ for­tunes large­ly rest on the po­ten­tial of its TKI Cabome­tyx (cabozan­ti­nib) in the treat­ment of re­nal cell and he­pa­to­cel­lu­lar car­ci­no­ma. Top-line re­sults from the Check­mate-9ER tri­al, eval­u­at­ing cabozan­ti­nib plus Bris­tol-My­er’s $BMY PD-1 Op­di­vo, ver­sus Pfiz­er’s $PFE suni­tinib, are ex­pect­ed in the first half of 2020.

But com­pe­ti­tion is fierce. Mer­ck’s $MRK Keytru­da has been ap­proved in com­bi­na­tion with Pfiz­er’s TKI In­ly­ta for RCC pa­tients, as has Ger­man Mer­ck’s check­point in­hibitor, Baven­cio, (in com­bi­na­tion with In­ly­ta) for the pa­tient pop­u­la­tion.

So­cial im­age: Shut­ter­stock

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.