FDA gives Cel­lec­tis a green light to re­launch off-the-shelf CAR-T stud­ies — with sev­er­al strings at­tached

Two months af­ter the FDA forced Cel­lec­tis $CLLS to hit the brakes on a pair of clin­i­cal tri­als for their off-the-shelf CAR-T UCART123, reg­u­la­tors have fol­lowed up with a green light to re­sume test­ing. But they’re adding some key safe­ty mea­sures to try to re­duce any out­stand­ing risks for pa­tients in these high pro­file stud­ies.

Cel­lec­tis CEO An­dré Chouli­ka

The tri­al halt came on the death of the first pa­tient dosed with UCART123. Now in­ves­ti­ga­tors can be­gin again. But there are some ex­tra­or­di­nary strings that are now at­tached:

  •  The co­hort dose lev­el has been lim­it­ed to 6.25×104 UCART123 cells/kg.
  • En­roll­ment has to be stag­gered, with a 28-day gap be­tween en­roll­ment of 2 pa­tients in the 2 stud­ies, ev­i­dent­ly to bet­ter con­trol how many pa­tients are ex­posed to risk.
  • The cy­clophos­phamide dose of the lym­pho-de­plet­ing reg­i­men — for prep­ping pa­tients — has been reined in to 750 mg/m²/day over three days with a max­i­mum dai­ly dose of 1.33 grams of cy­clophos­phamide.
  • Reg­u­la­tors want to make sure there’s no un­con­trolled fever af­ter lym­phode­ple­tion.
  •  The next three pa­tients in each pro­to­col has to be un­der 65 years of age.

Share of Cel­lec­tis, helmed by CEO An­dré Chouli­ka, shot up 24%.

Paris-based Cel­lec­tis was forced in­to a halt back on Sep­tem­ber 4, af­ter a pa­tient died on the launch of tri­als for acute myeloid leukemia and blas­tic plas­ma­cy­toid den­drit­ic cell neo­plasm.

The last time there was a tri­al halt in CAR-T, the FDA wait­ed just days to give Juno Ther­a­peu­tics a sig­nal to get their study for JCAR015 re­launched, on­ly to see sev­er­al of the next set of pa­tients die. That first halt came with no new lim­its aside from a re­stric­tion on the treat­ment reg­i­men used to prep pa­tients for a per­son­al­ized CAR-T. The sec­ond halt led to the elim­i­na­tion of JCAR015 as a vi­able drug can­di­date.

While the first gen­er­a­tion of per­son­al­ized CAR-T drugs us­ing pa­tients’ cells has been be­set from the be­gin­ning with signs of cy­tokine re­lease syn­drome and neu­ro­tox­i­c­i­ty, reg­u­la­tors and de­vel­op­ers have grown steadi­ly more con­fi­dent of their abil­i­ty to screen pa­tients and low­er risks. Cel­lec­tis, which is us­ing a new ap­proach to de­vel­op uni­ver­sal CAR-T drugs that can at­tack liq­uid can­cers, has a whole new set of de­mands to meet as in­ves­ti­ga­tors look for the next big step for­ward in the field.

And they’ll be scru­ti­nized every step of the way back.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.