D-day: No­var­tis ar­rives at a cross­road in the block­buster race to win the first FDA OK for CAR-T

Three years of in­tense com­pe­ti­tion and bil­lions of dol­lars in in­vest­ments in­to de­vel­op­ing the world’s first CAR-T ther­a­py has come down to the wire to­day with the first FDA pan­el re­view for No­var­tis’ lead­ing CTL019 (ti­s­agen­le­cleu­cel) ther­a­py.

Ob­servers crowd­ed in­to the pre­sen­ta­tion room this morn­ing, rub­bing shoul­ders with CAR-T celebs like Penn’s Carl June with many, many more look­ing on­line as No­var­tis and reg­u­la­tors be­gan the painstak­ing process of break­ing down the man­u­fac­tur­ing process that goes in­to the lengthy and com­plex task in­volved in mak­ing these drugs. While most of these pan­el re­views come down to as­sess­ing the da­ta and how re­sults stack up against the gold stan­dard on safe­ty and ef­fi­ca­cy, the agency to­day wants their ex­perts to care­ful­ly con­sid­er if these drugs can con­sis­tent­ly be made to or­der in a safe fash­ion by man­u­fac­tur­ers who are still fine tun­ing their de­liv­ery times. In ad­di­tion, they’ll need to dis­cuss the po­ten­tial threat of a tox­i­c­i­ty pro­file that has yet to be ful­ly es­tab­lished or com­plete­ly un­der­stood.

But they’ll be putting all that in­to con­text of a new ther­a­py that of­fers a break­through ap­proach in treat­ing ad­vanced can­cers for pa­tients with few, if any, op­tions. And they’ll be do­ing it at a time that the FDA has com­mit­ted it­self to ac­cel­er­at­ing the de­vel­op­ment of ma­jor new ther­a­pies un­der FDA com­mis­sion­er Scott Got­tlieb.

Brad Lon­car, an in­vestor who runs the $CN­CR im­munother­a­py ETF, cap­tured the key is­sues in an ear­ly tweet from the meet­ing.

Vic­tor Lu at the FDA was giv­en the mis­sion of ex­plain­ing the process of ex­tract­ing cells from pa­tients, en­gi­neer­ing them with chimeric anti­gen re­cep­tors and then whip­ping that in­to a ther­a­peu­tic punch in­volv­ing tens of mil­lions of T cells. While No­var­tis and the close run­ner up in the field have been man­u­fac­tur­ing CAR-T for rel­a­tive­ly small num­bers of tri­al sub­jects, No­var­tis is ask­ing for an OK to shift in­to the com­mer­cial sphere.

No­var­tis has ex­pe­ri­enced fail­ures in mak­ing ther­a­peu­tic dos­es for all of its pa­tients. And it’s been work­ing hard to get the vein-to-vein time down to about 22 days, ac­cord­ing to to­day’s tes­ti­mo­ny. If they get a pos­i­tive vote to­day, and a sub­se­quent for­mal OK, look for plen­ty of care­ful com­par­isons among the lead­ers in the field to see who can do the best job on man­u­fac­tur­ing.

Arie Bellde­grun, Kite CEO

Kite CEO Arie Bellde­grun, whose team will be up for re­view in com­ing months, dis­count­ed the horse race lan­guage that I have used just about week­ly as the lead­ers in CAR-T racked up progress and set­backs. In a blog post to­day, he said he’d be watch­ing as a lead cheer­leader for the ri­val team at No­var­tis.

The talk of a “race” makes for great prose, but my desk isn’t cov­ered in bet­ting sheets. It’s cov­ered in stacks of sci­en­tif­ic pa­pers that shows the promise of CAR-T tech­nol­o­gy. Stacks that are grow­ing. With every pa­per I read, it be­comes more and more clear that CAR-T is not a biotech race to be won, but rather a rev­o­lu­tion­ary ther­a­py to be ex­plored and ap­plied to oth­er can­cers. That’s a task larg­er than any sin­gle com­pa­ny.

Bellde­grun worked hard to be the first up for an FDA pan­el re­view, de­layed by de­mands for more ma­ture re­sults. But there is one ad­van­tage, from a horse race per­spec­tive, in its po­si­tion as a run­ner up. A win for No­var­tis to­day will make Kite’s task of win­ning ap­proval much more straight­for­ward. Kite, though, will like­ly have to field even more point­ed ques­tions about cere­bral ede­ma, which re­cent­ly killed one pa­tient in a clin­i­cal tri­al and de­railed the lead ther­a­py at Juno.

There’s plen­ty of dra­ma ahead — and not just in the vote to come up lat­er in the af­ter­noon.

I’ll keep you post­ed.


Im­age: to­day’s FDA pan­el Brad Lon­car

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Dave Barrett, Brian Chee, Amir Nashat, Amy Schulman. Polaris

Bob Langer's first port of call — Po­laris Part­ners — maps $400M for ninth fund

Health and tech ven­ture group Po­laris Part­ners, which counts Alec­tor, Al­ny­lam and Ed­i­tas Med­i­cine as part of its port­fo­lio, is set­ting up its ninth fund, rough­ly two years af­ter it closed Po­laris VI­II with $435 mil­lion in the bank, sur­pass­ing its tar­get by $35 mil­lion.

The Boston-based firm, in an SEC fil­ing, said it in­tends to raise $400 mil­lion for the fund. Po­laris — which rou­tine­ly backs com­pa­nies mold­ed out of the work done in the lab of pro­lif­ic sci­en­tist Bob Langer of MIT  — typ­i­cal­ly in­vests ear­ly, and sticks around till com­pa­nies are in the green. Like its peers at Flag­ship and Third Rock, Po­laris is all about cham­pi­oning the lo­cal biotech scene with a steady flow of start­up cash.

Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Partners Innovation Fund

David de Graaf now has his $28.5M launch round in place, build­ing a coen­zyme A plat­form in his lat­est start­up

Long­time biotech ex­ec David de Graaf has the cash he needs to set up the pre­clin­i­cal foun­da­tion for his coen­zyme A me­tab­o­lism com­pa­ny Comet. A few high-pro­file in­vestors joined the ven­ture syn­di­cate to sup­ply Comet with $28.5 mil­lion in launch mon­ey — enough to get it two years in­to the plat­form-build­ing game, with­in knock­ing dis­tance of the clin­ic.

Canaan jumped in along­side ex­ist­ing in­vestor Sofinno­va Part­ners to co-lead the round, with par­tic­i­pa­tion by ex­ist­ing in­vestor INKEF Cap­i­tal and new in­vestor BioIn­no­va­tion Cap­i­tal.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.

UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.