Ying Huang, Legend Biotech CEO

UP­DAT­ED: Leg­end scraps tri­al of its fol­low-up au­tol­o­gous CAR-T weeks af­ter clin­i­cal hold was lift­ed

Six weeks af­ter get­ting its clin­i­cal hold lift­ed, Leg­end Biotech has de­cid­ed to ter­mi­nate the Phase I study of its CAR-T tar­get­ing CD4+.

The news was tucked in­to an SEC fil­ing, and Leg­end con­firmed to End­points News in an email that the US study of LB1901 was scrapped, as well as a sep­a­rate in­ves­ti­ga­tor-ini­ti­at­ed Phase I study in Chi­na of a sim­i­lar prod­uct (LCAR-T2C) us­ing the same CAR pro­tein.

On­ly one pa­tient had been en­rolled in Leg­end’s Phase I study and the biotech nev­er re­sumed the tri­al af­ter the Feb­ru­ary clin­i­cal hold was lift­ed in late-May, a com­pa­ny spokesper­son told End­points.

Li­da Pacaud

“The de­ci­sion to ter­mi­nate the pro­gram was made based on a lack of clin­i­cal ben­e­fit from a sim­i­lar Leg­end Biotech CAR-T prod­uct can­di­date that ex­pressed the same CAR pro­tein as LB1901 and a de­sire to pri­or­i­tize oth­er prod­uct can­di­dates in our pipeline,” VP of clin­i­cal de­vel­op­ment Li­da Pacaud told End­points in an emailed state­ment.

LB1901 is an au­tol­o­gous CAR-T that was be­ing test­ed in pa­tients with re­lapsed or re­frac­to­ry T-cell lym­phoma. The tri­al had ex­pect­ed to en­roll 50 pa­tients and com­plete pri­ma­ry out­come da­ta col­lec­tion in De­cem­ber 2023, ac­cord­ing to the fed­er­al tri­als data­base.

LB1901 was cleared for an IND in De­cem­ber 2020, and the tri­al be­gan in Sep­tem­ber 2021. Af­ter en­rolling on­ly one pa­tient — who showed low CD4+ T-cell counts — the FDA placed a clin­i­cal hold on the study in Feb­ru­ary. The agency said the IND did not “con­tain suf­fi­cient in­for­ma­tion re­quired” to as­sess the ther­a­py’s risks to pa­tients.

The one pa­tient to have re­ceived LB1901 “con­tin­ues to do well and has not ex­pe­ri­enced any se­ri­ous ad­verse events,” a Leg­end spokesper­son said in an email to End­points. The pa­tient had failed two pri­or lines of ther­a­py.

The treat­ment, which takes cells from the pa­tient, was the fur­thest in the pipeline be­hind Leg­end and part­ner John­son & John­son’s Carvyk­ti, the sec­ond BC­MA CAR-T ap­proved by the FDA, which is al­so au­tho­rized in Eu­rope for pa­tients with mul­ti­ple myelo­ma.

Fur­ther down the pipeline, Leg­end re­ceived FDA clear­ance last month to be­gin a Phase I tri­al of LB1908, an­oth­er au­tol­o­gous CAR-T. The treat­ment se­lec­tive­ly tar­gets Claudin18.2 and will be test­ed in pa­tients with re­lapsed or re­frac­to­ry gas­tric, esophageal and pan­cre­at­ic can­cers.

Ed­i­tor’s note: This sto­ry was up­dat­ed to in­clude ad­di­tion­al in­for­ma­tion from a Leg­end spokesper­son. 

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Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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David Reese, Amgen R&D chief

UP­DAT­ED: In a fresh dis­ap­point­ment, Am­gen spot­lights a ma­jor safe­ty is­sue with KRAS com­bo

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, just two weeks after submitting a supplemental BLA. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Steve Paul, Karuna Therapeutics CEO (Third Rock)

Karuna's schiz­o­phre­nia drug pass­es a close­ly-watched PhI­II test, will head to FDA in mid-2023

An investigational pill that combines a former Eli Lilly CNS compound with an overactive bladder drug was better than placebo at reducing a scale of symptoms experienced by patients with schizophrenia in a Phase III trial.

Karuna Therapeutics’ drug passed the primary goal in EMERGENT-2, the Boston biotech said early Monday morning, alongside quarterly earnings. The study is the first of Karuna’s four Phase III clinical trials to read out in schizophrenia and will provide the backbone to the biotech’s first drug approval application, slated for mid-2023.

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GSK and IQVIA launch plat­form of US vac­ci­na­tion da­ta, show­ing drop in adult rates

Throughout the Covid-19 pandemic, the issue of vaccine uptake has been a point of contention, but a new platform from GSK and IQVIA is hoping to shed more light on vaccine data, via new transparency and general awareness.

The two companies have launched Vaccine Track, a platform intended to be used by public health officials, medical professionals and others to strengthen data transparency and display vaccination trends. According to the companies, the platform is intended to aid in increasing vaccine rates and will provide data on trends to assist public health efforts.

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