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: 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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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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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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As­traZeneca gains EU nod for di­a­betes triple; Am­gen and Duke launch re­al-world PC­SK9 ob­ser­va­tion­al study

→ Weeks after winning EU approval to start marketing dapagliflozin as Forxiga, AstraZeneca has racked up another OK for a triplet combo involving the SGLT2 diabetes drug. Named Qtrilmet, the pill combines Forxiga with the DPP-4 inhibitor Onglyza (saxagliptin) and the bedrock drug metformin in a modified-release format. That 3-in-1 approach proved superior in reducing average blood glucose levels to a number of other dual combinations across 5 Phase III trials, including Forxiga plus metformin, Onglyza with metformin, or glimepiride with metformin.

Five drugs, in­clud­ing two No­var­tis ther­a­pies, win EMA en­dorse­ment

As is custom, an EMA panel on Friday issued its weekly recommendations on marketing applications submitted by drug developers. This week, the agency backed the use of five new therapies — including two Novartis drugs — but issued no negative reviews.

Novartis’ S1P drug for relapsing forms of multiple sclerosis (MS) drug, Mayzent (known chemically as siponimod), which was approved by the FDA in March — has been given the nod by the EMA. The Swiss drugmaker already sells its other MS drug, Gilenya, in both regions.

Atom­wise's X-37 spin­out gets $14.5 mil­lion to launch AI dis­cov­ery ef­forts

The folks behind Atomwise’s spinout X-37 like to think in cosmological metaphors, and you can think of their AI drug development model as probes sent into space from a central station. That station just got $14.5 million in Series A funding from DCVC Bio, Alpha Intelligence Capital and Hemi Ventures to back those missions.

X-37 uses Atomwise’s AI platform to identify drug targets and – unlike the parent company, which largely sticks to computers  – bring those into a wet lab and preclinical testing.  In addition to AI professionals, it’s led in by part by drug developers from Velocity Pharmaceutical Development.

Ab­bott Lab­o­ra­to­ries CEO Miles White pass­es ba­ton down to suc­ces­sor; Lon­za CEO Marc Funk hits the ex­it

→ Abbott Laboratories has named a successor to CEO Miles White after he announced that he was stepping down in March after 21 years of service. Robert Ford, the company’s COO and president, will take the helm. Ford is known for his work in the $25 billion merger between St. Jude Medical into Abbott in January 2017. White will remain with the company as executive chairman of the board. 

→ After snapping up Novartis’ Swiss facility, Novartis Center of Excellence, in July, Lonza has announced that their CEO, Marc Funk, is hitting the exit for “personal reasons.” Funk has been the CEO of the company for less than a year — brought onto the company back in March. In the meantime, chairman Albert Baehny will serve as interim CEO. 

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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