Cell & Gene weekly
DMD Gene therapy fail, Allo-NK data, In Vivo CAR-T data published in Blood, and more...
What I read this week
» Pfizer announced gene therapy fordadistrogene movaparvovec did not hit primary or secondary endpoints in their Ph III clinical trial in ambulatory boys aged 4-7 yrs with Duchenne muscular dystrophy (DMD)… The trial was already on hold due to the death of a young boy in their DAYLIGHT trial, for boys 2-3 yrs old. A sad day for patients and their families. - Source: Fiercebiotech
» Affimed / Artiva published data on their combo trial, LuminICE-203, evaluating AFM13, an innate cell engager, with AB-101, an allo NK cell therapy, in r/r Hodgkin lymphoma. 6 of 7 patients (85.7%) responded, of which 4 were complete responses (57%) . Albeit early data, this is supported by the previous study from the MD Anderson study which in which 32 patients were enrolled. Considering a median baseline of 4 lines of prior treatment the data bodes well. -Source: AffimedIR
» Umoja bio published data in Blood, highlighting generation of in vivo CAR T-cells in Non-Human Primate; whats particularly neet is that even in the absence of lymphodepleting chemo, their lentiviral particles, dubbed VivoVec, successfully generated CAR positive T cells targeting CD20 in vivo leading to depletion of B cells in excess of 10 weeks. - Source: UmojaIR; Blood
» Ultragenyx announced plans to file for accelerated approval of UX111 AAV gene therapy for Sanfilippo Syndrome Type A (MPS IIIA) after reaching an agreement with FDA that CSF heparan sulfate can be a reasonable surrogate for approval. The biotech now plans to finalize the details of its filing at a meeting with the FDA and apply for approval either late in 2024 or early in 2025. - source: Fiercebiotech
» Cabaletta Bio Reported VERY preliminary data from Ph1/2 RESET-Myositis and SLE Trials of their CABA-201 cell therapy. When I mean very preliminary, its data for 1 SLE patient and 1 Myositis patient… Since when do public companies report n=2 patient data… Anyhow, therapy seems to have been well tolerated, and both patients showed improvement in specific disease measures → chronic maintenance therapies were discontinued, except for a planned steroid taper. For now the CAR-T autoimmune story holds 😉 - source: EULAR symposium slides
CAR-T cell therapy trial tracker
~12 new CAR-T studies posted on clinical trials.gov in the past few week.
7 CAR-T in heme: (1) Essen Biotech CD5/CD7 CAR-T in Leukemia [link]; (2) Vittoria Bio CD5 CAR-T in NHL [link]; (3) Essen Bio CD33/CD123 CAR-T in AML [link]; (4) Shenzhen Geno-Immune Medical Institute combined BCMA and GPRC5D “multi-CAR-T cells” in MM and Plasmacytoma [link]; (5) Shangai Cell therapy group’s CD19/CD22/BCMA CAR-T in NHL [link]; (6) Rong Tao’s CD19/CD22 CAR-T in ALL or NHL [link]; (7) City of Hope CD19 CAR-T in Leukemia [link]
5 CAR-Ts in autoimmune: (1) Gracell CD19/BCMA CAR-T in Myasthenia Gravis [link]; (2) Shanghai First Song Therapeutics CD-19 in autoimmune diseases [link]; (3) Essen biotech BCMA/CD19 CAR-T in r/r autoimmune disease [link]; (4) Atara bio Allo CD19 CAR-T in Lupus [link]; (5) Kyverna CD19 CAR-T in Multiple Sclerosis [link]
Given IQVIA institute have recently published their Oncology research and developemtn activities report, lets also take a step back and look at the overall trial landscape for CAR-Ts (oncology only here): 264 trials were started investigating the use of CAR Ts in oncology in 2023, similar to levels over the prior two years; however, solid tumor trial starts nearly doubled while hematological cancer trial starts remained flat over the last five years
Source: Clinicaltrials.gov; IQVIA report
Interesting reads
STAT NEWS - Europe is set to shake up the way it assesses new medicines. Gene therapy makers are worried
THE CONVERSATION - When there’s no commercial incentive to develop gene therapy – hospitals will try to fill the gap —> Great Ormond Street Hospital (Gosh) will explore for the first time if an NHS hospital can plug the gap for UK patients
NATURE MEDICINE- PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial —> Prostate-specific antigen declines (>30%) occurred in 4 of 14 patients, as well as radiographic improvements
*Any views and opinions expressed herein are those of the author (Marco Sabatini) and do not necessarily reflect those of his employer