Af­ter ran­corous threats and a clin­i­cal hold, Ap­plied Ther­a­peu­tics is set to re­sume pe­di­atric galac­tosemia study

Af­ter an anony­mous re­port raised red flags over Ap­plied Ther­a­peu­tics’ in­tegri­ty in Ju­ly, say­ing the com­pa­ny “cher­ry picked” da­ta and os­ten­si­bly prompt­ing a short at­tack, the biotech ac­cused the au­thors of the re­port of fraud and threat­ened le­gal ac­tion. Then, a month lat­er, the FDA in­di­cat­ed it al­so had con­cerns over its lead galac­tosemia pro­gram, slap­ping a clin­i­cal hold on a study test­ing their can­di­date in chil­dren.

But on Mon­day, reg­u­la­tors hand­ed down some good news and lift­ed the hold on the tri­al, Ap­plied an­nounced. The study is ex­pect­ed to re­sume “ef­fec­tive im­me­di­ate­ly,” the com­pa­ny said in a state­ment.

At the time the hold was placed, Ap­plied of­fered few clues as to why the FDA pressed the pause but­ton. On Mon­day, the com­pa­ny said that ex­ecs met with the agency to mod­i­fy the tri­al in a way that en­sures all pa­tients re­ceive a “clin­i­cal ben­e­fit.”

The pro­gram had pre­vi­ous­ly con­sist­ed of two sep­a­rate tri­als — a dose es­ca­la­tion and bio­mark­er study, fol­lowed by a sep­a­rate long-term clin­i­cal out­comes study. Those parts have now been com­bined in­to a sin­gle, two-part tri­al that al­lows each pa­tient in the dose es­ca­la­tion por­tion to con­tin­ue in­to the long-term por­tion with­out in­ter­rupt­ing their treat­ments.

Every­one who was al­ready ran­dom­ized and par­tic­i­pat­ing in the study will be el­i­gi­ble to re­turn, and Ap­plied says they’ll be ful­ly en­rolled “with­in a mat­ter of weeks.”

Though last sum­mer’s hold did not af­fect the pa­tients from the piv­otal tri­al on adults, it pushed back the time­line for a po­ten­tial ap­proval. Ap­plied had orig­i­nal­ly shot for an NDA in the sec­ond half of 2020, but at the time of the hold pushed back that goal to the first quar­ter of 2021.

With Mon­day’s news, Ap­plied $APLT said it plans to sub­mit an NDA in the third quar­ter of this year. Shares rose 21% in Mon­day trad­ing.

Ap­plied’s pro­gram, dubbed AT-007, in­hibits the en­zyme al­dose re­duc­tase and can cross the blood brain bar­ri­er to en­ter the cen­tral ner­vous sys­tem, the com­pa­ny says. Pa­tients with galac­tosemia have trou­ble break­ing down the sug­ar galac­tose in their blood­streams and can suf­fer from tox­ic waste that builds up in tis­sues and or­gans that cause long-term com­pli­ca­tions.

In Jan­u­ary of last year, they un­veiled piv­otal da­ta that AT-007 re­duced galac­tose by around 50% when com­pared to place­bo. But the short at­tack hit the com­pa­ny in Ju­ly af­ter the full re­sults came out. Among the ac­cu­sa­tions Ap­plied made in­clud­ed “fab­ri­cat­ed graphs and fraud­u­lent da­ta” aimed at ma­nip­u­lat­ing the com­pa­ny’s stock price.

Such at­tacks are not un­com­mon in biotech and com­pa­nies rou­tine­ly shake them off, but Ap­plied raised more red flags with the ac­tions it took fol­low­ing the re­port.

Bahija Jallal, Immunocore CEO

BREAK­ING: FDA hur­ries up a quick ap­proval for the world's first TCR -- af­ter a 14-year R&D trek

Over the 14 years since Immunocore was spun out of MediGene in a quest to develop a gamechanging cancer med, the biotech has raised record sums and undergone a major shakeup on a long roller coaster ride of valuations for investors. But they survived and thrived and today they’re popping the champagne corks to celebrate an FDA approval of their first TCR drug.

Immunocore flagged the FDA’s green light for tebentafusp Wednesday morning by highlighting a series of firsts.

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Days af­ter Gilead yanks PI3K drug, In­cyte with­draws NDA for its own PI3K — say­ing con­fir­ma­to­ry tri­als would take too long

The FDA’s intensifying scrutiny on accelerated approvals isn’t just putting pressure on drugmakers with marketed products. It is also subtly reshaping the regulatory dynamics.

Case in point: Incyte announced late Tuesday that it has made the “business decision” to withdraw an NDA for parsaclisib, its oral PI3Kδ inhibitor, after deciding that running the confirmatory studies the agency was asking for to support an accelerated approval wouldn’t be worth it.

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In a set­back, FDA or­ders Gilead to hit the brakes on their late-stage, $5B can­cer play

Gilead’s $5 billion drug magrolimab has run into a serious setback.

The FDA ordered Gilead to halt enrollment on their studies of the drug in combination with azacitidine after investigators reports revealed an “apparent imbalance” in the suspected unexpected serious adverse reactions between study arms. And the halt is raising questions about Gilead’s plans for a quick pitch to regulators.

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A new can­cer im­munother­a­py brings cau­tious hope for a field long await­ing the next big break­through

Bob Seibert sat silent across from his daughter at their favorite Spanish restaurant near his home in Charleston County, SC, their paella growing cold as he read through all the places in his body doctors found tumors.

He had texted his wife, a pediatric intensive care nurse, when he got the alert that his online chart was ready. Although he saw immediately it was bad, many of the terms — peritoneal, right iliac — were inscrutable. But she was five hours downstate, at a loud group dinner the night before another daughter’s cheer competition.

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Dominic Borie, Kyverna Therapeutics CEO

Well-con­nect­ed, Gilead-backed biotech gets an­oth­er stack of cash to pur­sue CAR-Ts for au­toim­mune dis­ease

Almost exactly two years after its debut at the 2020 JP Morgan confab — and on the heels of a new partnership with the gene editing experts at Intellia — a Gilead-backed, autoimmune disease-focused startup has returned to the well with a clearer outline of just what it plans to do with its CAR-T platform.

Kyverna brought in $85 million in its oversubscribed Series B, the company announced Wednesday. Northpond Ventures led the round, and Westlake Village BioPartners, Vida Ventures, Gilead and Intellia all contributed as well.

Graphic: Alexander Lefterov for Endpoints News

Small biotechs with big drug am­bi­tions threat­en to up­end the tra­di­tion­al drug launch play­book

Of the countless decisions Vlad Coric had to make as Biohaven’s CEO over the past seven years, there was one that felt particularly nerve-wracking: Instead of selling to a Big Pharma, the company decided it would commercialize its migraine drug itself.

“I remember some investors yelling and pounding on the table like, you can’t do this. What are you thinking? You’re going to get crushed by AbbVie,” he recalled.

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Mar­ket­ingRx roundup: Pfiz­er de­buts Pre­vnar 20 TV ads; Lil­ly gets first FDA 2022 pro­mo slap down let­ter

Pfizer debuted its first TV ad for its Prevnar 20 next-generation pneumococcal pneumonia vaccine. In the 60-second spot, several people (actor portrayals) with their ages listed as 65 or older are shown walking into a clinic as they turn to say they’re getting vaccinated with Prevnar 20 because they’re at risk.

The update to Pfizer’s blockbuster Prevnar 13 vaccine was approved in June, and as its name suggests is a vaccine for 20 serotypes — the original 13 plus seven more that cause pneumococcal disease. Pfizer used to spend heavily on TV ads to promote Prevnar 13 in 2018 and 2019 but cut back its TV budgets in the past two fall and winter seasonal spending cycles. Prevnar had been Pfizer’s top-selling drug, notching sales of just under $6 billion in 2020, and was the world’s top-selling vaccine before the Covid-19 vaccines came to market last year.

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UP­DAT­ED: FDA slams Eli Lil­ly's 'mis­lead­ing' In­sta­gram ad for its type 2 di­a­betes in­jec­tion

In a first for 2022, the FDA’s Office of Prescription Drug Promotion has issued an untitled letter, which was recently sent to Eli Lilly over what the agency calls a “misleading” and “particularly concerning” Instagram ad the company posted for its type 2 diabetes drug Trulicity.

The questionable Instagram post, which has since been deleted by Lilly, failed to adequately communicate the indication and limitations of use associated with Trulicity, FDA says.

US re­stricts use of two mon­o­clon­al an­ti­bod­ies that don't work against Omi­cron

Two monoclonal antibody combos from Eli Lilly and Regeneron are no longer authorized in the US, and shipments to states have ceased because HHS said they are “highly unlikely” to work against the sweeping new variant Omicron.

The move by the FDA comes as states like Florida have become insistent that the mAbs need to be independently evaluated, although the federal Department of Health and Human Services, which has shipped hundreds of thousands of these two mAbs to states in recent weeks, did not ship any this week.