Pa­tient death forces FDA to slap a hold on study us­ing com­bo from Ad­vax­is, As­traZeneca -- biotech's shares plunge

The FDA has slapped a clin­i­cal hold on a com­bo ther­a­py us­ing Ad­vax­is’ $ADXS ax­al­imo­gene filolis­bac along with As­traZeneca’s ap­proved PD-L1 Imfinzi fol­low­ing the death of a pa­tient in their Phase I/II tri­al.

Re­searchers were study­ing the com­bi­na­tion of drugs for pa­tients with HPV-trig­gered head-and-neck as well as cer­vi­cal can­cer. In this par­tic­u­lar case, a pa­tient died from res­pi­ra­to­ry fail­ure fol­low­ing the 6th treat­ment cy­cle. And now reg­u­la­tors want to put the study on hold while they ex­am­ine the im­pli­ca­tions for oth­ers in the tri­al.

The news trig­gered a sharp 31% drop in Ad­vax­is’ shares af­ter the mar­ket closed.

An­tho­ny Lom­bar­do

The two de­vel­op­ers part­nered more than three years ago, while Imfinzi was still an ex­per­i­men­tal ther­a­py. The As­traZeneca drug works by tak­ing the brakes off an im­mune sys­tem at­tack on can­cer cells. Ad­vax­is’ drug us­es a live, en­gi­neered strain of Lm bac­te­ria to kick up an im­mune re­sponse while tar­get­ing de­fen­sive mech­a­nisms in can­cer cells. Just a few days ago Ad­vax­is filed for con­di­tion­al mar­ket­ing ap­proval in the EU for use against cer­vi­cal can­cer.

Ad­vax­is learned about the hold on Fri­day, 10 days af­ter the pa­tient’s death.

In a quar­ter­ly call with an­a­lysts on Mon­day, Ad­vax­is’ Robert Pet­tit ex­plained that the pa­tient has been in the study for more than a year. He added:

So in this par­tic­u­lar case, she re­ceived her first drug which was dur­va. She start­ed de­vel­op­ing some med­ical prob­lems in be­tween that were man­aged, then she start­ed to re­ceive the sec­ond dose. Af­ter­wards, she re­ceived the sec­ond drug, which was AX­AL. She was be­ing man­aged for hy­poten­sion ag­gres­sive­ly and was sub­se­quent­ly hos­pi­tal­ized. While she was hos­pi­tal­ized, she de­vel­oped res­pi­ra­to­ry fail­ure and sub­se­quent­ly ex­pired de­spite meth­ods to stop the pro­gres­sion of her dis­ease. That’s re­al­ly all the in­for­ma­tion we have at this point.

While tri­al deaths in stud­ies us­ing CAR-T drugs are not un­usu­al, the check­points have been go­ing in­to hun­dreds of com­bi­na­tion stud­ies with­out rais­ing a lot of safe­ty is­sues — aside from com­bos us­ing Cel­gene’s Revlim­id and Po­m­a­lyst with Mer­ck’s Keytru­da, where an im­bal­ance in pa­tient deaths trig­gered con­cern. That caused a blan­ket pull­back in­volv­ing sim­i­lar check­point com­bos, but af­ter the FDA de­ter­mined there like­ly was no class ef­fect in­volved, most of those stud­ies were al­lowed to get back in­to the clin­ic.

Ad­vax­is is al­so part­nered with Bris­tol-My­ers on an Op­di­vo com­bi­na­tion pro­gram, which fol­lowed a sep­a­rate al­liance with Am­gen.

This isn’t the first study us­ing their drug, and the biotech tried to re­as­sure in­vestors about its safe­ty.

“We care deeply for our pa­tients and for their safe­ty as we work to re­search and de­vel­op new treat­ment op­tions for ad­vanced can­cers. We be­lieve in the po­ten­tial of our Lm Tech­nol­o­gy to pro­vide new ad­vance­ments in the area of can­cer care,” said Ad­vax­is CEO An­tho­ny Lom­bar­do in a state­ment. “We are con­fi­dent in the safe­ty and ef­fi­ca­cy pro­file of ax­al­imo­gene filolis­bac, to date, based on our ex­pe­ri­ence in over 250 pa­tients and over 700 dos­es across mul­ti­ple tri­als in HPV-as­so­ci­at­ed can­cers.”

Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

Seer adds ex-FDA chief Mark Mc­Clel­lan to the board; Her­cules Cap­i­tal makes it of­fi­cial for new CEO Scott Bluestein

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Daniel O'Day

No­var­tis hands off 3 pre­clin­i­cal pro­grams to the an­tivi­ral R&D mas­ters at Gilead

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.

Vas Narasimhan, AP Images

On a hot streak, No­var­tis ex­ecs run the odds on their two most im­por­tant PhI­II read­outs. Which is 0.01% more like­ly to suc­ceed?

Novartis CEO Vas Narasimhan is living in the sweet spot right now.

The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

Year-to-date the stock is up 28%, so the investors will be beaming. Anyone looking for chinks in their armor — and there are plenty giving it a shot — right now focus on payer acceptance of their $2.1 million gene therapy Zolgensma, where it’s early days. And CAR-T continues to underperform, but Novartis doesn’t appear to be suffering from it.

So what could go wrong?

Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

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On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.