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.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Sanofi and GSK reach deal with Cana­da for 72 mil­lion vac­cine dos­es

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the biotech.

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Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Isaac Veinbergs, Libra CEO

With $29M in Se­ries A, Boehringer-backed Li­bra looks to tack­le neu­rode­gen­er­a­tion through cel­lu­lar clean­ing

Can the natural process by which cells clean out toxic proteins be harnessed to create potential treatments for neurodegenerative disorders?

That’s the question Libra Therapeutics will be trying to answer, as the new biotech officially launched Wednesday morning with $29 million in Series A financing. The company has three preclinical programs at the ready, with its lead candidate targeting ALS and frontotemporal dementia. But CEO Isaac Veinbergs said he hopes to develop therapies for a wide range of diseases, including Parkinson’s, Alzheimer’s and Huntington’s.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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