Recent data readouts in cell and gene therapies highlight promising advancements in treating various diseases, including mucopolysaccharidosis type II (MPSII), spinal muscular atrophy (SMA), diffuse large B-cell lymphoma (DLBCL), and X-linked retinitis pigmentosa (XLRP).
REGENXBIO's RGX-121 Shows Long-Term Efficacy in MPSII
REGENXBIO's RGX-121, an investigational adeno-associated virus (AAV) vector-based gene therapy for MPSII (Hunter syndrome), continues to demonstrate efficacy in long-term data from the phase 1/2/3 CAMPSIITE clinical trial (NCT03566043). Presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium 2024, the data showed a median reduction of 85% in heparan sulfate (HS) D2S6 levels in the cerebrospinal fluid (CSF) among patients who received the pivotal dose level (DL3). These levels approached normal and were sustained for up to two years.
Notably, 80% of patients treated at DL3 remained off standard-of-care enzyme replacement therapy (ERT) for up to 18 months post-gene therapy. Additionally, 71% of patients treated at DL2 were ERT-free for nearly three years after treatment.
Biogen's Nusinersen Demonstrates Efficacy at Higher Dose in SMA
Biogen's nusinersen (Spinraza), an antisense oligonucleotide (ASO) therapy for SMA, has shown improved efficacy compared to a sham treatment when administered at a higher dose. Data from the pivotal part B cohort of the phase 2/3 DEVOTE clinical trial (NCT04089566) revealed that a higher dose regimen resulted in a statistically significant improvement in Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores at 6 months posttreatment (least squares mean difference: 26.19; P < .0001) compared to a matched, untreated sham control group from the phase 3 ENDEAR clinical trial (NCT02193074). The experimental higher dose included two 50-mg loading doses 14 days apart, followed by 28-mg maintenance doses every four months, contrasting with the FDA-approved 12-mg loading and maintenance doses.
Allogeneic CAR-T Azer-Cel Shows Promise in DLBCL
Azercabtagene zapreleucel (azer-cel), an investigational allogeneic CAR-T therapy, has demonstrated complete responses (CRs) in some patients with relapsed/refractory (r/r) DLBCL in a phase 1/1b clinical trial (NCT03666000) run by Imugene. In cohort B, where patients received azer-cel with interleukin 2 (IL-2) following lymphodepletion, 2 out of 3 evaluable patients achieved CRs (67%), with one ongoing for over 120 days and another for over 90 days. In cohort A, the overall response rate was 33%, with 17% achieving a CR and 1 patient achieving a partial response; however, the durability of response was less than 60 days.
Beacon Therapeutics' AGTC-501 Maintains Favorable Profile in XLRP
Beacon Therapeutics' AGTC-501, an AAV vector-based gene therapy for XLRP, continues to exhibit a favorable benefit-risk profile based on updated data from the phase 1/2 HORIZON clinical trial (NCT03316560), presented at the 24th EURETINA Congress. Among 29 patients, there were no suspected unexpected serious adverse reactions (SUSARS) or endophthalmitis. Most treatment-emergent adverse events (TEAEs) were not serious. Ocular serious AEs (SAEs) included retinal detachment (4 cases), subcapsular cataract (1 case), reduced visual acuity (1 case), and glaucoma (1 case), primarily related to the injection procedure or perioperative steroids. Approximately 73% of ocular TEAEs occurred within the first three months post-treatment, with most resolving within a month.
