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.”

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

15 LGBTQ lead­ers in bio­phar­ma; Paul Stof­fels’ Gala­pa­gos re­vamp; As­traZeneca catch­es up in AT­TR; 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.

A return to in-person conferences also marks a return to on-the-ground reporting. My colleagues Beth Synder Bulik and Nicole DeFeudis were on-site at Cannes Lions, bringing live coverage of pharma’s presence at the ad festival — accompanied by photos from Clara Bui, our virtual producer, that bring you right to the scene. You can find a recap (and links to all the stories) below.

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Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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GSK says its drug for chron­ic hep B could ‘lead to a func­tion­al cure’ — but will it be alone or in com­bi­na­tion?

GSK, newly branded and soon-to-be demerged, shared interim results from its Phase II trial on its chronic hepatitis B treatment, one that it says has the “potential to lead to a functional cure.”

At a presentation at the EASL International Liver Congress, GSK shared that in around 450 patients who received its hep B drug bepirovirsen for 24 weeks, just under 30% had hepatitis B surface antigen and viral DNA levels that were too low to detect.

Sanofi, GSK tout 72% Omi­cron ef­fi­ca­cy in PhI­II tri­al of next-gen, bi­va­lent shot — with an eye to year-end roll­out

Sometimes, being late can give you an advantage.

That’s what Sanofi and GSK are trying to say as the Big Pharma partners report positive results from a late-stage trial of their next-gen bivalent Covid-19 vaccine, which was designed to protect against both the original strain of the SARS-CoV-2 virus and the Beta variant. Specifically, against Omicron, they note, the vaccine delivered 72% efficacy in all adults and 93.2% in those previously infected.

Matt Kapusta, uniQure CEO

In trou­bled Hunt­ing­ton’s space, uniQure’s gene ther­a­py shows ear­ly promise

In randomized clinical trial data from a small number of patients, Dutch biotech uniQure shared that its gene therapy for Huntington’s disease seems to reduce the amount of the mutant protein responsible for the disease over the course of a year.

In seven patients with early-stage Huntington’s — four who got the treatment and three who got a placebo — mutant huntingtin protein levels in the cerebrospinal fluid decreased by an average of just over 50% in patients who got the gene therapy compared to around a 17% drop in patients who got the placebo after a year.

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De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.