Stung by pa­tient deaths, a small Juno study points to a Goldilocks for­mu­la for CAR-T

For Juno, the hunt to find just the right mix­ture of T cells along with an ef­fec­tive reg­i­men to prep pa­tients for their CAR-T ther­a­py has had a lethal his­to­ry, tan­gling up de­vel­op­ment time­lines in a way that has ced­ed the lead in the field to ri­val Kite.

Stan­ley Rid­dell

But in a new, small study in­volv­ing one of their most ad­vanced CAR-Ts, an in­ves­tiga­tive team feels that they came up with just the right recipe. And that could have big im­pli­ca­tions for an­oth­er CAR-T pro­gram in which Juno holds high hopes for a come­back.

The drug in­volved in the study is called JCAR014, and the in­ves­ti­ga­tors say that they came up with a one-on-one mix of CD4+ helper cells with CD8+ killer cells that showed a re­mark­able abil­i­ty to wipe out can­cer cells that ex­press CD19, which has been the big ini­tial tar­get for all the play­ers in the van­guard of CAR-T work.

Sig­nif­i­cant­ly, the in­ves­ti­ga­tors al­so con­clud­ed that adding flu­dara­bine to cy­clophos­phamide (Cy/Flu) in a cock­tail to prep pa­tients cre­ates the right en­vi­ron­ment for the T cells to grow in the body. Half of the 18 pa­tients with non-Hodgkin lym­phoma who got the Cy/Flu com­bo had a com­plete re­sponse to the ther­a­py, com­pared to on­ly 8% of the group who re­ceived on­ly cy­clophos­phamide.

The team point­ed out that these re­sults could in­di­cate sim­i­lar out­comes for JCAR017, which is now in ear­ly stud­ies. Juno has tapped JCAR017 as a po­ten­tial “best-in-class” treat­ment for blood can­cers.

The mes­sage helped buoy the com­pa­ny’s stock to­day, send­ing shares up about 3%.

“With the de­fined com­po­si­tion treat­ment, we are able to get more re­pro­ducible da­ta about the ef­fects of the cells — both the ben­e­fi­cial im­pact against the can­cer and any side ef­fects to the pa­tient,” said Fred Hutch clin­i­cal re­searcher Stan Rid­dell, one of the se­nior au­thors of the pa­per, along with Dr. David Mal­oney. “We are then able to ad­just the dose to im­prove what we call the ther­a­peu­tic in­dex — im­pact against the tu­mor, with low­er tox­i­c­i­ty to the pa­tient.”

The ad­di­tion of flu­dara­bine to Juno’s lead CAR-T, JCAR015, was fin­gered for killing four pa­tients, a set­back for the biotech which trig­gered a brief but dam­ag­ing clin­i­cal hold by the FDA. The hold last­ed on­ly days, end­ing with the FDA sign­ing off on the biotech’s de­ci­sion to drop flu­dara­bine. But the hold end­ed up forc­ing Juno to de­lay its ex­pect­ed move to file for their first ap­proval back to 2018. Kite, mean­while, which is us­ing its own mix of T cells and Cy/Flu, has said it ex­pects to take the first batch of da­ta from its lead­ing study to the FDA af­ter an ini­tial re­view that comes in just a mat­ter of weeks.

This new study from Juno al­so rais­es ques­tions about its lead drug, JCAR015. If pa­tient out­comes are sig­nif­i­cant­ly low­ered by the ab­sence of flu­dara­bine, Juno’s first at­tempt at a com­mer­cial en­try against the com­pe­ti­tion could be se­vere­ly af­fect­ed.

CAR-Ts be­came a hot field a cou­ple of years ago, at­tract­ing hun­dreds of mil­lions in new in­vest­ments as the front run­ners raced to ad­vance new reme­dies for can­cer by adding a chimeric anti­gen re­cep­tor to a pa­tient’s T cells and then in­fus­ing them back in­to the pa­tient. But with Juno’s de­rail­ment and a re­cent de­ci­sion by No­var­tis to dis­solve its cell and gene ther­a­py unit and re­ab­sorb it in­to their big on­col­o­gy di­vi­sion, all eyes are on Kite now to see if it can claim the first ap­proval and mar­ket en­try.

The stakes are high.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.

Vas Narasimhan. Getty Images

Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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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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Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.

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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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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