Deaths spur par­tial hold for Xen­cor’s CD3 bis­pe­cif­ic for leukemia, part­nered with No­var­tis in $2.5B deal

Re­searchers at Xen­cor have slammed the brakes on re­cruit­ing more pa­tients for an ear­ly-stage study of XmAb14045, a CD123 x CD3 bis­pe­cif­ic an­ti­body in the race for acute myeloid leukemia. 

The com­pa­ny says that the FDA dropped the hold on them af­ter they tracked 2 deaths in the study that could be linked to the bis­pe­cif­ic — one from cy­tokine re­lease syn­drome and an­oth­er from acute pul­monary ede­ma fol­low­ing sev­er­al dos­es. The CRS case was com­pli­cat­ed by the pa­tient’s de­ci­sion to with­draw from the study, ac­cord­ing to the com­pa­ny.

Bassil Dahiy­at

CD3 bis­pecifics are all the rage these days, in­spir­ing a $2.5 bil­lion deal with No­var­tis back in 2016 that was front­ed with a $150 mil­lion cash pay­ment. That gave the phar­ma gi­ant dibs on XmAb14045 and XmAb13676. Iron­i­cal­ly, No­var­tis opt­ed to hand back rights to XmAb13676 just weeks ago while keep­ing its ties with Xen­cor $XN­CR on ‘14045.

This isn’t the first time a CD123 x CD3 has run in­to a clin­i­cal hold. J&J’s AML study for JNJ-63709178 was put on a full hold by the FDA back in 2016 — though the com­pa­ny wouldn’t say at the time what ad­verse events were in­volved. Macro­Gen­ics, mean­while, had its own par­tial hold to deal with for its B7-H3 × CD3 bis­pe­cif­ic late last year af­ter re­searchers spot­ted signs of liv­ery tox­i­c­i­ty in pa­tients.

Now you can ex­pect plen­ty of more ques­tions about what kind of safe­ty is­sues these bis­pecifics pose as de­vel­op­ers race each oth­er to the fin­ish line. That could be es­pe­cial­ly trou­bling for Xen­cor, par­tic­u­lar­ly af­ter J&J dropped it drug ta­la­co­tuzum­ab (JNJ-56022473/CSL362) for acute myeloid leukemia in 2017. That Phase III drug, orig­i­nal­ly from CSL, us­es Xen­cor’s an­ti­body tech.

Bassil Dahiy­at, pres­i­dent and chief ex­ec­u­tive of­fi­cer at Xen­cor, not­ed this morn­ing: 

“We are work­ing with the in­ves­ti­ga­tors and the FDA and will pro­vide an up­date when more in­for­ma­tion about re­sum­ing en­roll­ment can be shared. Our on­go­ing Phase 1 stud­ies eval­u­at­ing our oth­er CD3 bis­pe­cif­ic an­ti­bod­ies, XmAb13676 and XmAb18087, are not af­fect­ed.”

An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Can an FDA hus­tle up on trastuzum­ab be far be­hind?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Mer­ck Serono’s Se­nior Vice Pres­i­dent and Glob­al Head of On­col­o­gy
EL­LIOTT LEVY — Am­gen’s Se­nior Vice Pres­i­dent of Glob­al De­vel­op­ment
CHRIS BOSHOFF — Pfiz­er On­col­o­gy’s Chief De­vel­op­ment Of­fi­cer

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Ver­sant-backed Chi­nook gets a $65M launch round for its dis­cov­ery quest in a resur­gent kid­ney field

Versant is once again stepping off the beaten track in biotech to see if they can blaze a trail of their own in a field that has looked too thorny to many investors for years.

The venture group and their partners at Apple Tree are bringing their latest creation out of stealth mode today. Born in Versant’s Inception Sciences’ Chinook Therapeutics is betting that its preclinical take on kidney disease can get an early lead among the companies starting up in the field.

Sir An­drew Dil­lon, NICE's first — and on­ly — chief ex­ec­u­tive to step down next year

Using a laptop borrowed from his former employer, South London’s St George’s Hospital, Sir Andrew Dillon set about establishing NICE — launched by the then health secretary Frank Dobson — in 1999.  On Thursday, the UK cost-effectiveness watchdog said its first and only chief executive — Dillon — is stepping down in March 2020.

Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.

Eight weeks be­tween each HIV treat­ment? GSK notch­es PhI­II win as it chas­es OK for long-act­ing reg­i­men

GSK has cleared another test in its grand plan to topple Gilead’s HIV dominance by offering alternative treatments that consist of fewer drugs and last longer. A year after scoring positive Phase III data on a four-week course of cabotegravir and rilpivirine, its ViiV subsidiary now says that an eight-week regimen seem to work just as well.

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Finch grabs a $53M round de­signed to take their ‘break­through’ mi­cro­bio­me treat­ment through a po­ten­tial­ly piv­otal tri­al

With a breakthrough designation in one hand and a fresh $53 million in venture backing in the other, Somerville, MA-based Finch Therapeutics is taking a shot at a one-trial pathway to a possible FDA OK for their new treatment for preventing recurrent C. difficile infections.

The funding brings their total raise for the microbiome company to $130 million, CEO Mark Smith tells me — enough money to pave a runway past the FDA approval they’ve sketched into the most optimistic version for their near-term future. 

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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