Af­ter Kite Phar­ma stuns an­a­lysts with news of a death in lead CAR-T study, safe­ty ques­tions sour launch fore­cast

There may nev­er have been a right way for Kite Phar­ma to an­nounce that a pa­tient in one of its CAR-T stud­ies died from cere­bral ede­ma — but wait­ing more than a week and then bring­ing it up on the quar­ter­ly call with an­a­lysts def­i­nite­ly wasn’t the way to go. That route seems to have on­ly bright­ened the glar­ing spot­light that im­me­di­ate­ly swiveled over to com­pa­ny ex­ecs as they tried to ex­plain, and down­play, the death.

David Nieren­garten, Wed­bush an­a­lyst

To­day, in a note to in­vestors, Wed­bush an­a­lyst David Nieren­garten high­light­ed the mine field that Kite — which saw its shares plunge 13% yes­ter­day — is try­ing to nav­i­gate on this top­ic.

While Kite CMO David Chang re­peat­ed­ly em­pha­sized in the call just how sick this pa­tient was be­fore he died, Nieren­garten sees some dis­turb­ing sim­i­lar­i­ties with Juno’s old lead drug, JCAR015, which im­plod­ed in Phase III af­ter it killed 5 peo­ple in two dif­fer­ent groups — be­fore and af­ter a clin­i­cal hold by the FDA.

In his note to in­vestors this morn­ing, Nieren­garten said:

We al­so see the death as ad­di­tion­al ev­i­dence against the use of CD28 co-stim­u­la­to­ry do­mains in CAR-T de­signs — re­call, JUNO scrapped its CD28-con­tain­ing CAR-T JCAR015 pro­gram that caused mul­ti­ple fa­tal­i­ties due to cere­bral ede­ma in the ROCK­ET study of adult ALL pa­tients. We see high risk for safe­ty prob­lems in axi-cel’s on­go­ing stud­ies in adult and pe­di­atric ALL pa­tients, as well as for pipeline CAR-Ts KITE-585 (BC­MA) and KITE-796 (CLL-1/CLEC12A) that both uti­lize a CD28 co-stim­u­la­to­ry do­main.

David Chang, Kite

While Kite ex­ecs, led by CEO Arie Bellde­grun, want to fo­cus on near-term op­por­tu­ni­ties for a lead CAR-T that’s neck-and-neck with No­var­tis in seek­ing a pi­o­neer­ing FDA OK, Nieren­garten sees in­creased risk — even with an ex­pect­ed ap­proval. And ri­vals may well com­pli­cate the pic­ture even more at the up­com­ing AS­CO meet­ing.

“We see adop­tion as be­ing lim­it­ed by physi­cian aware­ness and com­fort re­gard­ing risk/ben­e­fit pro­file,” notes Nieren­garten. “We see lit­tle push­back from pay­ers, giv­en the lim­it­ed ini­tial pa­tient pop­u­la­tion and one-time na­ture of the treat­ment, and as­sume the price re­ceived by KITE from each pro­ce­dure to be $325k. We await da­ta from Juno’s (JUNO, NEU­TRAL) JCAR017 at AS­CO, as well as NVS’s CAR-T CTL019 Juli­et study at ICML in June to gain fur­ther in­sight in­to mar­ket dy­nam­ics go­ing for­ward.”

Arie Bellde­grun

Juno nev­er did ful­ly ex­plain just what went wrong with JCAR015. It’s first ex­pla­na­tion, try­ing to pin the blame on flu­dara­bine, was clear­ly off base. Long time ob­servers nev­er thought that was cred­i­ble. And Juno wound up shelv­ing the whole thing and go­ing the next-wave ap­proach with JCAR017.

It didn’t help that two top Kite ex­ecs, in­clud­ing Chang, cashed in some stock op­tions be­tween the time they learned of the death and the time it was an­nounced. Those sales may have been pro­grammed in well ahead of time, but the op­tics are al­ways bad.

Kite now has lit­tle room for er­ror. The risk of an­oth­er lethal cere­bral ede­ma case pop­ping up is cre­at­ing doubts just when Kite needs to ex­ude con­fi­dence and cer­tain­ty.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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Sanofi takes a $260M hit to ex­tri­cate it­self from a dis­as­trous al­liance with Lex­i­con

Sanofi spent $300 million in cash to get into a $1.7 billion alliance with Lexicon on their SGLT1/2 diabetes drug sotagliflozin. And now that the drug has been spurned by the FDA after burning through a program that provided mixed late-stage data and a late shot at a last-place finish, the French pharma giant is forking over another $260 million to get out of the deal.

Sanofi’s unhappiness was already apparent when the company — now under new CEO Paul Hudson — posted a statement back in July that they were dropping the deal. But it wasn’t that simple. 

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.