Christi Shaw, JPM19 (Credit: Jeff Rumans)

#AS­CO21: A week af­ter nab­bing pri­or­i­ty re­view, Kite un­veils the piv­otal da­ta it hopes will lead to a new CAR-T ap­proval

Just less than a year ago, Gilead’s Kite won a land­mark okay for its sec­ond CAR-T ther­a­py, with da­ta that for­mer head of glob­al de­vel­op­ment Ken Takeshi­ta hailed as “bet­ter than Yescar­ta.” Now, ahead of #AS­CO21, Kite is un­veil­ing piv­otal da­ta to back the drug in a new type of can­cer.

Frank Neu­mann

Of 55 pa­tients who re­ceived Tecar­tus for re­lapsed or re­frac­to­ry B-cell pre­cur­sor acute lym­phoblas­tic leukemia (ALL), 71% saw their signs of can­cer dis­ap­pear, new head of clin­i­cal de­vel­op­ment Frank Neu­mann said. How­ev­er, some still had in­com­plete hema­to­log­ic re­cov­ery (which the com­pa­ny de­fined as com­plete re­sponse with in­com­plete hema­to­log­ic re­cov­ery, or CRi).

Thir­ty-one per­cent of these pa­tients saw on­go­ing re­spons­es at the da­ta cut­off, Kite said, and 97% had deep mol­e­c­u­lar re­mis­sion with un­de­tectable min­i­mal resid­ual dis­ease.

“This pa­tient pop­u­la­tion in par­tic­u­lar has a very ham­pered hematopoi­et­ic sys­tem,” Neu­mann told End­points News. “I would say, for a pa­tient reach­ing CRi in this par­tic­u­lar in­di­ca­tion, it’s fan­tas­tic, to say the least.”

The da­ta come from a pri­ma­ry analy­sis of the Phase II por­tion of Kite’s open-la­bel ZU­MA-3 tri­al. Just un­der half of the treat­ed pa­tients had re­ceived three or more ther­a­pies pri­or to Tecar­tus, and among the 25 who had tak­en the im­munother­a­py bli­na­tu­momab, the com­plete re­sponse rate was a bit low­er, com­ing in at just 60%.

Across the whole treat­ment arm, me­di­an du­ra­tion of re­sponse, re­lapse-free sur­vival and over­all sur­vival were 12.8 months, 11.6 months and 18.2 months, re­spec­tive­ly.

The FDA gave Tecar­tus pri­or­i­ty re­view for the in­di­ca­tion last Fri­day, and set a PDU­FA date of Oct. 1. If ap­proved, CEO Christi Shaw says the com­pa­ny could start rolling out the drug in days.

The treat­ment comes with some risk, as 95% of pa­tients ex­pe­ri­enced Grade 3 or high­er ad­verse events, the most fre­quent be­ing ane­mia and pyrex­ia, or fever. Grade 3 or high­er cy­tokine re­lease syn­drome — a well-doc­u­ment­ed side ef­fect of CAR-T ther­a­py — oc­curred in 24% of pa­tients.  Neu­ro­log­ic events hap­pened in 25%, Kite said.

CRS and neu­ro­log­ic tox­i­c­i­ties earned Tecar­tus a boxed warn­ing in re­lapsed/re­frac­to­ry man­tle cell lym­phoma, though re­searchers saw low­er cas­es of Grade 3 or high­er CRS in that study than in ZU­MA-3 (18% com­pared to 24%). CRS cas­es in Zu­ma-3 were “gen­er­al­ly re­versed with treat­ment,” Kite said in a state­ment.

Two treat­ment-re­lat­ed deaths oc­curred in ZU­MA-3, in­clud­ing one brain her­ni­a­tion and one case of sep­tic shock, ac­cord­ing to Kite’s state­ment.

The safe­ty pro­file of Tecar­tus in this par­tic­u­lar in­di­ca­tion doesn’t dif­fer sig­nif­i­cant­ly from what we’ve seen in oth­er in­di­ca­tions,” Neu­mann said.

Up­on its ap­proval last year, a Kite spokesper­son told End­points that the drug would be sold for $373,000. Since then, the list price has in­creased to just un­der $400,000, Shaw said. Tecar­tus brought in $31 mil­lion in Q1, as launch ac­tiv­i­ties ramped up in the US, ac­cord­ing to Gilead’s fi­nan­cial re­sults.

“As long as we have these re­al­ly long durable re­spons­es, and we can man­u­fac­ture con­sis­tent­ly, and con­tin­ue with Frank’s lead­er­ship de­vel­op­ing new ther­a­pies that help in­crease the ben­e­fit/risk for pa­tients, I think that’s the se­cret sauce,” she said.

While ZU­MA-3 en­rolled pa­tients 18 years and old­er, No­var­tis’ CAR-T ri­val Kym­ri­ah is al­ready ap­proved to treat re­lapsed/re­frac­to­ry ALL in pa­tients 25 years old and younger, and it’s cur­rent­ly in a Phase III tri­al for high-risk ALL in the same pop­u­la­tion.

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

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

The slate of products we’re offering here at Endpoints is continuing to grow, and it’s not just limited to editorial. If you haven’t, do visit your reader profile to see if there are any other weekly newsletters you’re interested in — as each comes with its own exclusive content. And don’t miss the publisher’s note from Arsalan Arif on Endpoints Studio, our latest avenue for advertising on Endpoints.

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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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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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Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

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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