FDA ad­vis­ers back No­var­tis’ game-chang­ing per­son­al­ized CAR-T for can­cer, ap­proval in sight

The FDA’s ad­vi­so­ry com­mit­tee on can­cer drugs has of­fered a group thumbs-up for No­var­tis’ trail­blaz­ing CAR-T CTL019 (ti­s­agen­le­cleu­cel), mark­ing a key mile­stone for the phar­ma gi­ant as it nears the like­ly launch of a ground­break­ing per­son­al­ized cell ther­a­py for B-cell acute lym­phoblas­tic leukemia.

These out­side ex­perts at the FDA vot­ed 10 to 0 to urge an ap­proval for this drug, of­fer­ing some key sup­port af­ter reg­u­la­tors care­ful­ly re­viewed the com­plex man­u­fac­tur­ing process as well as the safe­ty and ef­fi­ca­cy pro­files of this ther­a­py.

Key to No­var­tis’ suc­cess was the high re­mis­sion rate as well as 6-month and 12-month sur­vival da­ta for chil­dren and young adult pa­tients who were run­ning out of op­tions. The pa­tient num­bers were small, but the re­spons­es were ex­tra­or­di­nary for the pa­tients who re­spond­ed, with an 83% over­all re­mis­sion rate and 79% over­all sur­viv­abil­i­ty rate at 12 months – hit­ting the pri­ma­ry end­point.

“This is a nov­el ther­a­py, there’s an un­met med­ical need, a strong ef­fi­ca­cy and a good risk mit­i­ga­tion strat­e­gy,” not­ed com­mit­tee mem­ber James Gul­ley from the Na­tion­al Can­cer In­sti­tute.

Alan Rein from the Cen­ter for Can­cer Re­search cit­ed the drug’s “re­mark­able clin­i­cal suc­cess­es,” though he not­ed some lin­ger­ing con­cerns with the long-term risks in­volved. And oth­ers echoed those re­marks, rais­ing the prospect that CAR-T can be a game-chang­er in this field.

David Leb­wohl

David Leb­wohl, No­var­tis’ chief of the CTL019 pro­gram, told the pan­el ear­li­er in the day that these out­comes were un­like any­thing he’d seen in 20 years of prac­tice.

But this ther­a­py is al­so linked with threat­en­ing side ef­fects. While pa­tients on this en­gi­neered CAR cell ther­a­py have been re­peat­ed­ly hit by po­ten­tial­ly lethal cas­es of cy­tokine re­lease syn­drome and neu­ro­log­i­cal tox­i­c­i­ty with the threat of new ma­lig­nan­cies, ad­vis­ers were clear­ly will­ing to ac­cept the risk in or­der to achieve the po­ten­tial gains. There were no cas­es of cere­bral ede­ma, in­ves­ti­ga­tors not­ed, but oth­er CAR-Ts have been linked to such cas­es.

No­var­tis al­so not­ed the death of a pa­tient from a cere­bral he­m­or­rhage. Al­so, 9 pa­tients had to dis­con­tin­ue the tri­al af­ter CTL019 couldn’t be man­u­fac­tured for them – a key short­fall that No­var­tis will have to man­age care­ful­ly if it gets a green light for man­u­fac­tur­ing.

Sev­er­al of the com­mit­tee mem­bers, though, of­fered No­var­tis a vote of con­fi­dence on their risk mit­i­ga­tion strat­e­gy and the abil­i­ty of spe­cial­ists in the field to han­dle side ef­fects.

The last three years of de­vel­op­ment work at No­var­tis has been marked by or­ga­ni­za­tion­al re­struc­tur­ing along with the ad­vance and re­treat of ri­val ther­a­pies – all while sort­ing through a threat­en­ing list of tox­i­c­i­ty fac­tors. But No­var­tis’ team main­tained their lead, de­liv­er­ing on a promise No­var­tis CEO Joe Jimenez made to per­sist with the de­vel­op­ment of a dra­mat­ic new ap­proach to treat­ing can­cer.

Ob­servers crowd­ed in­to the FDA’s pre­sen­ta­tion room this morn­ing, rub­bing shoul­ders with CAR-T celebs like Penn’s Carl June with many, many more look­ing on on­line. But the re­view in­volves more than just one ther­a­py at one com­pa­ny. The ad­vis­ers gath­ered at a time that the FDA has com­mit­ted it­self to ac­cel­er­at­ing the de­vel­op­ment of ma­jor new ther­a­pies un­der new FDA com­mis­sion­er Scott Got­tlieb, and CTL019 will be viewed as a test case for the agency’s open­ness to new ther­a­pies that are not yet thor­ough­ly probed in ad­vanced clin­i­cal tri­als.

The vote al­so un­der­scores ODAC’s in­grained ac­cep­tance of mod­er­ate risk when it comes to treat­ing pa­tients dy­ing of can­cer.

Close on No­var­tis’ heels is a team from Kite, a CAR-T-fo­cused biotech which had hoped to be the first to the mar­ket. Kite to­day got a front row seat to the way the agency views these ther­a­pies, and it’s like­ly to take ad­van­tage of that in its own up­com­ing reg­u­la­to­ry re­view.

Be­hind them comes Juno, with a new lead drug, and a group of play­ers like Cel­lec­tis, which are in the ear­ly stages of de­vel­op­ing what they hope can be off-the-shelf ther­a­pies that should be less ex­pen­sive to make and mar­ket.

Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors. 

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

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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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.

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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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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H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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