FDA fol­lows through with a ground­break­ing OK for Yescar­ta, Gilead­'s new CAR-T break­through

Just two weeks af­ter Gilead closed on its $12 bil­lion Kite buy­out, the FDA has fol­lowed through with a ground­break­ing ap­proval of Yescar­ta (axi-cel), putting its CAR-T drug neck-and-neck with No­var­tis’ pi­o­neer Kym­ri­ah as the two drugs are prepped for a launch.

In a vir­tu­al heart­beat, Gilead used its con­sid­er­able cash re­serves to reach a deal to buy out Kite and axi-cel 6 weeks ago, ac­quir­ing its new­ly ap­proved CAR-T and all the next-gen tech­nol­o­gy now in the works. The ac­qui­si­tion made Gilead an overnight leader in CAR-T. While beat­en to a his­toric first FDA ap­proval for a CAR-T by an ag­gres­sive group at No­var­tis — ini­tial­ly green-light­ed at the end of Au­gust for pe­di­atric and young adult pa­tients with a form of acute lym­phoblas­tic leukemia — Gilead is re­tain­ing most of the Kite gang and hon­ing its man­u­fac­tur­ing ef­fort, shav­ing off the time it takes to turn around these per­son­al­ized ther­a­pies.

In clas­sic ag­gres­sive form, Gilead came out gun­ning, of­fer­ing the ther­a­py at a price of $373,000 — $102,000 less than its ri­val at No­var­tis. On the oth­er hand, No­var­tis of­fered a val­ue-based deal to a num­ber of pay­ers in which they on­ly get re­im­burse­ment for pa­tients who re­spond to ther­a­py, evening the play­ing field.

Once again, FDA com­mis­sion­er Scott Got­tlieb took the hon­ors in con­grat­u­lat­ing the de­vel­op­ers, as he did when No­var­tis came out in front. And this time, he promised to lend the agency’s help for the rest of the bur­geon­ing cell ther­a­py field. Said Got­tlieb:

“To­day marks an­oth­er mile­stone in the de­vel­op­ment of a whole new sci­en­tif­ic par­a­digm for the treat­ment of se­ri­ous dis­eases. In just sev­er­al decades, gene ther­a­py has gone from be­ing a promis­ing con­cept to a prac­ti­cal so­lu­tion to dead­ly and large­ly un­treat­able forms of can­cer. This ap­proval demon­strates the con­tin­ued mo­men­tum of this promis­ing new area of med­i­cine and we’re com­mit­ted to sup­port­ing and help­ing ex­pe­dite the de­vel­op­ment of these prod­ucts. We will soon re­lease a com­pre­hen­sive pol­i­cy to ad­dress how we plan to sup­port the de­vel­op­ment of cell-based re­gen­er­a­tive med­i­cine. That pol­i­cy will al­so clar­i­fy how we will ap­ply our ex­pe­dit­ed pro­grams to break­through prod­ucts that use CAR-T cells and oth­er gene ther­a­pies. We re­main com­mit­ted to sup­port­ing the ef­fi­cient de­vel­op­ment of safe and ef­fec­tive treat­ments that lever­age these new sci­en­tif­ic plat­forms.”

The CD19 T cell im­munother­a­py — which reengi­neers pa­tient cells in­to a po­tent can­cer ther­a­py — has been ap­proved for adult pa­tients with re­lapsed or re­frac­to­ry large B-cell lym­phoma af­ter two or more lines of sys­temic ther­a­py. That la­bel in­cludes dif­fuse large B-cell lym­phoma (DL­B­CL), pri­ma­ry me­di­asti­nal large B-cell lym­phoma, high-grade B-cell lym­phoma, and DL­B­CL aris­ing from fol­lic­u­lar lym­phoma.

Alessan­dro Ri­va

The R&D work will now be led by Alessan­dro Ri­va, a for­mer No­var­tis sci­en­tist pro­mot­ed yes­ter­day to ex­ec­u­tive vice pres­i­dent in charge of on­col­o­gy R&D, with a seat on the lead­er­ship team.

Left be­hind in the race to CAR-T dom­i­nance, for now at least, is Juno Ther­a­peu­tics. Its ri­val drug was mired down by a lethal tox­i­c­i­ty is­sue that killed 5 pa­tients, forc­ing the biotech to switch over to its num­ber 2 pro­gram.

No­var­tis man­aged to sur­prise quite a few an­a­lysts by peg­ging Kym­ri­ah at $475,000, which is sig­nif­i­cant­ly low­er than the $600,000 max­i­mum pro­vid­ed in some of the spreads. In a sto­ry we pub­lished yes­ter­day, how­ev­er, a num­ber of ex­perts said the full cost of ther­a­py may well end up at $1 mil­lion to $1.5 mil­lion.

The da­ta, though, are jaw drop­ping.

The FDA’s ap­proval comes through on the da­ta for ZU­MA-1, which demon­strat­ed that 72% of the pa­tients in­volved had an ob­jec­tive re­sponse rate to the ther­a­py. And 51% demon­strat­ed a com­plete re­mis­sion, with no sign of the can­cer left.

In a re­cent farewell let­ter to the staff, Kite CEO Arie Bellde­grun summed it up by writ­ing:

In a span of just a few short years, we grew from few­er than 10 em­ploy­ees to al­most 700. The com­pa­ny’s val­ue in­creased 2300% from the time of our IPO to near­ly $12 bil­lion with the ac­qui­si­tion by Gilead Sci­ences. Our clos­ing $180 per share price rep­re­sents not just a 960% ap­pre­ci­a­tion from the IPO price of $17 per share, but the largest ever pre-com­mer­cial bio­phar­ma ac­qui­si­tion.

Now Gilead can see if it’s ag­gres­sive team can make the most of the block­buster peak sales es­ti­mates that have yet to be climbed.

To­day, Bellde­grun had this to say:

“The FDA ap­proval of Yescar­ta is a land­mark for pa­tients with re­lapsed or re­frac­to­ry large B-cell lym­phoma. This ap­proval would not have been pos­si­ble with­out the coura­geous com­mit­ment of pa­tients and clin­i­cians, as well as the on­go­ing ded­i­ca­tion of Kite’s em­ploy­ees. We must al­so rec­og­nize the FDA for their abil­i­ty to em­brace and sup­port trans­for­ma­tion­al new tech­nolo­gies that treat life-threat­en­ing ill­ness­es. We be­lieve this is on­ly the be­gin­ning for CAR T ther­a­pies.”

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.