Tri­al ob­servers say ‘game over’ for XBiotech's failed PhI­II can­cer study, the lat­est in a long line of set­backs

There’s more bad news to re­port for XBiotech $XBIT.

A few weeks af­ter Eu­ro­pean reg­u­la­tors snubbed the com­pa­ny’s ap­pli­ca­tion to start mar­ket­ing its du­bi­ous can­cer drug Xilonix, the Austin-based biotech is back with the news that it’s halt­ing a Phase III colon can­cer study af­ter out­side ex­perts con­clud­ed it wasn’t work­ing.

Their con­clu­sion:

The IDMC had no safe­ty con­cerns from the un­blind­ed analy­sis. How­ev­er, the com­mit­tee rec­om­mend­ed the ear­ly ter­mi­na­tion of the study since the find­ings were not suf­fi­cient to meet ef­fi­ca­cy or the thresh­old for con­tin­u­a­tion, which in­volved a prospec­tive­ly de­fined ac­cep­tance bound­ary for the in­ter­im analy­sis of less than or equal to p = 0.08.

For the record, p=0.08 is a ter­ri­ble score. In­vestors got the mes­sage fast, and drove XBiotech’s shares down by a cap­i­tal crunch­ing 62% Fri­day af­ter­noon.

Very lit­tle about this drug, though, has gone right. Back in April the EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use flagged the mem­bers’ opin­ion that the da­ta just wasn’t there for an ap­proval. The for­mal CHMP opin­ion didn’t change. And its opin­ion was bru­tal.

The CHMP had a num­ber of con­cerns. First, the com­mit­tee not­ed that the study did not show clear im­prove­ments in ei­ther lean body mass or qual­i­ty of life. Sec­ond­ly, there was an in­creased risk of in­fec­tion in pa­tients tak­ing the med­i­cine, which was not con­sid­ered ac­cept­able in vul­ner­a­ble pa­tients who will be re­ceiv­ing pal­lia­tive care. Last­ly, there were in­ad­e­quate con­trols of the man­u­fac­tur­ing process to en­sure the med­i­cine would have the same qual­i­ty as the prod­uct used in clin­i­cal tri­als.

There­fore, the CHMP was of the opin­ion that the ben­e­fits of this med­i­cine did not out­weigh its risks and rec­om­mend­ed that it be re­fused mar­ket­ing au­tho­ri­sa­tion.

This was af­ter in­ves­ti­ga­tors re­port­ed that the Phase III was marred by a mix­up in treat­ing the place­bo and drug arms, a num­ber of dropouts and im­prop­er pa­tient eval­u­a­tions.

XBiotech CEO John Simard, though, im­me­di­ate­ly be­gan an ap­peal. And he’s not about to give up on this failed Phase III, ei­ther.

“We are ob­vi­ous­ly dis­ap­point­ed with these find­ings,” he said in a pre­pared state­ment. “In the com­ing weeks, the Com­pa­ny plans to an­a­lyze the da­ta ex­ten­sive­ly to fur­ther un­der­stand the pri­ma­ry and sec­ondary end­point da­ta, as well as to iden­ti­fy pop­u­la­tions that may have ben­e­fit­ed from the ther­a­py. These find­ings to­day will not af­fect our ef­forts to pur­sue ap­proval of the ther­a­py based on the suc­cess­ful com­ple­tion of the Eu­ro­pean study, which demon­strat­ed con­trol of de­bil­i­tat­ing symp­toms in col­orec­tal can­cer.”

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.