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.

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

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Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

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Federal Trade Commission commissioner Rohit Chopra testifies on Capitol Hill (AP Photo/Susan Walsh)

FTC clears Bris­tol-My­ers’ $74B deal to buy Cel­gene — but Dems sig­nal a po­ten­tial hard shift against Big Phar­ma M&A

Bristol-Myers Squibb’s record $74 billion takeover of Celgene is a done deal. And it will all be over — except for the lingering complaints from die-hard Celgene investors — on Wednesday.

Like much else that’s going on in Washington these days, the vote among the 5 FTC commissioners split along party lines, with the 3 Republicans voting to clear the way and the 2 Democrats steamed over what they see as a major M&A move that will lessen competition and innovation. And that split has big implications for the M&A side of the business if the Dems take the White House in 2020.

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No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

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No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

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BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: In a first, FDA green-lights use of a Chi­nese built can­cer ther­a­py — and more are com­ing

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

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What does $62B buy you these days? A lot, says Take­da ex­ecs as the phar­ma play­er promis­es a block­buster R&D fu­ture

First comes the $62 billion buyout. Then comes the asset auction and reorganization to pay down debt. Now comes the detailed pledge of a bigger, brighter future in drug development.

That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

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GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

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Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

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