And then there were 4: Juno adds an­oth­er vic­tim in CAR-T death tal­ly

Juno’s CAR-T drugs didn’t just kill three peo­ple in clin­i­cal tri­als. They ac­tu­al­ly killed 4, as the com­pa­ny notes in its “re­vised” re­marks from last week’s tran­script of a call with com­pa­ny an­a­lysts. And the fol­lowup rais­es the mys­tery of yet an­oth­er case of cere­bral ede­ma trig­gered by se­vere neu­ro­tox­i­c­i­ty, which may or may not have been re­port­ed by Juno.

Here’s the state­ment, post­ed with the tran­script in a fil­ing with the SEC:

Note to Re­vised Re­marks: (Chief Med­ical Of­fi­cer Dr. Mark) Gilbert mis­tak­en­ly said “three” cas­es out of 129 rather than “four” cas­es. The fourth case was a pa­tient treat­ed in the JCAR014 tri­al, which case oc­curred in a young adult pa­tient with r/r ALL who re­ceived flu/cy pre­con­di­tion­ing and a high­er JCAR014 cell dose than is now used on that tri­al. This death was in­clud­ed in the da­ta pre­sent­ed in an oral pre­sen­ta­tion at the Amer­i­can So­ci­ety of Hema­tol­ogy meet­ing in De­cem­ber 2015 and in­clud­ed in Juno’s An­nu­al Re­port on Form 10-K for the fis­cal year end­ed De­cem­ber 31, 2015.

Note to Re­vised Re­marks: As not­ed ear­li­er in the ques­tion and an­swer ses­sion, the FDA al­so re­port­ed an in­stance of cere­bral ede­ma in its data­base out­side of the JCAR015 tri­al. Juno does not know whether that in­stance is the same case of cere­bral ede­ma as Juno is aware of from the JCAR014 tri­al, or if it oc­curred on a tri­al for a non-Juno prod­uct can­di­date.

Juno trig­gered a rout among its in­vestors last week when it stunned the mar­ket with news that its lead CAR-T drug, JCAR015, had killed three peo­ple in clin­i­cal stud­ies, trig­ger­ing a clin­i­cal hold of its piv­otal study by the FDA. The com­pa­ny im­me­di­ate­ly blamed the re­cent ad­di­tion of the chemo drug flu­dara­bine to pre­con­di­tion pa­tients for the cell ther­a­py and of­fered to drop the drug. In one of the fastest re­spons­es by the FDA in the face of mul­ti­ple pa­tient deaths, the agency agreed and lift­ed the hold ear­li­er this week.

The per­son­al­ized brand of CAR-Ts that Juno, Kite, and No­var­tis have been de­vel­op­ing ex­tract im­mune cells from pa­tients, re-en­gi­neer them with a chimeric anti­gen re­cep­tor and then in­ject them back in­to pa­tients, equipped to swarm can­cer cells. These new treat­ments are al­so known to trig­ger cy­tokine re­lease syn­drome, which forced a tem­po­rary pause in the ex­per­i­men­tal work a cou­ple of years ago. But Juno be­lieves that the way that flu­dara­bine was used re­cent­ly caused the neu­ro­tox­i­c­i­ty that trig­gered cas­es of cere­bral ede­ma tracked by in­ves­ti­ga­tors.

Not every­one was as quick as the FDA to buy in­to that the­o­ry, though, as sev­er­al in­ves­ti­ga­tors note that flu­dara­bine has been used reg­u­lar­ly with­out ev­i­dence of cere­bral ede­mas. In ad­di­tion, ri­val Kite Ther­a­peu­tics has used a low dose of flu­dara­bine in its work and has no plans to change as it pur­sues its own piv­otal work.

The FDA, though, is not ex­plain­ing any­thing as of now, de­clin­ing to an­swer some spe­cif­ic ques­tions of mine.

“Cel­lu­lar ther­a­pies, in­clud­ing Chimeric Anti­gen Re­cep­tor (CAR) T-Cell ther­a­pies, hold great promise in the treat­ment of se­ri­ous and life-threat­en­ing dis­eases,” the agency said in a state­ment to End­points. “We there­fore do every­thing pos­si­ble to as­sist spon­sors in ad­vanc­ing clin­i­cal de­vel­op­ment pro­grams in an ef­fort to bring promis­ing ther­a­pies to pa­tients. The FDA rec­og­nizes that in­ves­ti­ga­tion­al prod­ucts in­tend­ed to treat se­ri­ous dis­eases al­so have the po­ten­tial to pose risks to pa­tients. To this end, the FDA con­stant­ly looks at the risk-ben­e­fit pro­file of ex­per­i­men­tal ther­a­pies and when we have con­cerns about the risks, we may place the clin­i­cal tri­als on hold.”

Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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One of Wall Street’s most high-pro­file hedge funds push­es Alex­ion's CEO to the auc­tion block — and he's not budg­ing

Fresh off buying Barnes & Noble and prodding AT&T with some heavy-handed criticism after picking up a $3.2 billion stake in the company, the activist — and supremely high profile — hedge fund Elliott Management has stepped up with some M&A advice for Alexion’s management team.
And the execs on the team $ALXN are giving them a polite — but very firm — stiff arm Friday morning.
In a release out early Friday, the big biotech said that the Elliott team had been in touch to encourage them to sell the company. But that’s not on the agenda.

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Un­lock the full End­points ex­pe­ri­ence for your com­pa­ny — and sup­port our mis­sion of in­de­pen­dent bio­phar­ma re­port­ing

I want to give readers a quick update on the most important part of our business model — premium subscriptions. We have some crucial financial goals we hope to achieve by the end of the year, and the team here in Lawrence is ready to ship some swag to kick off this limited December promotion.

We offer two premium plans — Enterprise for companies ($1,000/year, unlimited people), and Insider for individuals ($200/year). This month of December will be the last chance to enroll at the original rates — which have remained flat since we launched them in 2017.

Jasper Ther­a­peu­tics launch­es out of Stan­ford with new ap­proach to stem cell treat­ment

The first girl in the trial came in with chronic diarrhea and the immune system of an untreated HIV patient. Born with a rare genetic disease that impeded her ability to make B and T cells, she had once been given a stem cell transplant but it didn’t take.  Back in the hospital, she was injected with a new experimental antibody and then given a new stem cell transplant. Soon, she gained weight. The diarrhea stopped.

Samantha Budd Haeberlein. Biogen via YouTube

UP­DAT­ED: Skep­tics pounce as Bio­gen de­tails pos­i­tive sub­group analy­sis on ad­u­canum­ab — and both sides are dig­ging in

“Exhilarating.” “A major advance.” “A milestone achievement.” If one had just tuned into the panel comments on Biogen’s presentation at CTAD, it would seem that the biotech had an impressive, disease-modifying Alzheimer’s drug in aducanumab.

But off the stage, reactions to their admittedly complicated dataset and the biotech’s explanation for resurrecting a drug that failed its futility analysis were a lot more mixed, with analysts continuing to question whether the evidence is substantial enough to warrant an FDA approval and raising new doubts on the safety side.

In an investor call later in the day, execs noted that they are not planning another study and stood by their intention, publicized in October to much surprise, to submit regulatory filings based on what they have.

“We don’t file willy nilly,” said Al Sandrock, head of R&D. “We only go to filing when we believe that there is a benefit-risk argument based on science, based on data. And if you look at our history, we haven’t done filings right and left without good reason.”

Biogen had a theory going into the Clinical Trials on Alzheimer’s Disease meeting.

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No­var­tis CEO Vas Narasimhan's R&D up­date spot­lights next wave of drug stars as well as late-stage fa­vorites

As one of the biggest spenders in biopharma R&D, Novartis execs love to tout the scope of its late-stage pipeline, spotlighting the winners most likely to create blockbuster revenue streams in the near future.

Building on the 5 drug approvals the pharma giant expects to end the year with, Novartis CEO Vas Narasimhan — who’s done a slate of acquisitions topped by the recent $9.7 billion MedCo buyout — tapped the top emerging drugs as:

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Jeff Jonas, Sage

UP­DAT­ED: Sage's star ex­per­i­men­tal de­pres­sion drug fails the cru­cial MOUN­TAIN study — shares crash

Sage Therapeutics’ crucial MOUNTAIN study for Sage-217 has failed, setting the stage for a quick and ugly investor backlash.

Widely viewed by analysts as the critical clinical study $SAGE needed to win on major depression, researchers say the drug failed to beat out a placebo at day 15, falling well short of the mark for statistical significance on the primary endpoint. And investors reacted with alacrity, fleeing the stock and gutting the price with a 60% instantaneous drop — erasing about $4.6 billion in market cap in an instant.

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Ex-Cel­gene ex­ec Ter­rie Cur­ran puts her Phath­om team in place; Car­away taps Mar­tin Williams as CEO

→ Gastrointestinal disease-focused Phathom Pharmaceuticals has shaken up its leadership team. The company has tapped former Celgene exec Terrie Curran as CEO, succeeding David Socks, who is transitioning to interim CFO. Curran was president of Celgene’s global inflammation and immunology franchise — helping with the sale of Otezla for $13.4 billion to Amgen — and has held a previous stint at Merck. In addition to Curran, the company also welcomed former Omeros CMO Eckhard Leifke as CMO, ex-Celgene exec Joseph Hand as chief administrative officer, and former general counsel for Cyclerion Therapeutics Larry Miller as general counsel. They also replaced Chris Slavinsky on the board with Takeda exec Asit Parikh.

UCB buffs up in block­buster pso­ri­a­sis race as bimek­izum­ab beats Hu­mi­ra in head-to-head

Just weeks after boasting head-to-head victories over first placebo and then J&J’s IL-23 contender Stelara in clearing psoriasis, the results are in for UCB’s last Phase III trial, in which bimekizumab went up against the world’s best-selling drug.

Only topline results are provided for today’s readout of the BE SURE study, so we won’t find out just how superior bimekizumab proved against Humira on the co-primary endpoints — standard scores known as PASI90 and IGA measuring the impact and severity of the disease — until a scientific conference in 2020.