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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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