- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
Integrated analyses of data from clinical trials of delandistrogene moxeparvovec in DMD (Congress Hall, 2nd Floor) - May 29, 2023 - Abstract #EPNS2023EPNS_118;
P1, P1/2,
Delandistrogene moxeparvovec demonstrated a clinically meaningful and statistically significant difference versus a propensity-score-weighted EC cohort in change from baseline in NSAA total score at Year 1, suggesting a beneficial modification of the DMD disease trajectory. Collective safety data were consistent and manageable across studies.
- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
Phase 1/2a Trial of Delandistrogene Moxeparvovec in Patients with DMD: 4-year Update (Concourse Hall 150 & 151) - May 3, 2023 - Abstract #ASGCT2023ASGCT_2424;
P1/2
Patients treated with delandistrogene moxeparvovec generally maintained muscle strength (Time to Rise and 4-stair Climb) and showed improvement in ambulation ability (10-meter and 100-meter walk/run) from baseline to Year 3.The observed safety profile and the enduring response following treatment provide proof-of-concept for continuation of clinical trials assessing delandistrogene moxeparvovec using single-dose gene therapy in patients with DMD. We present the latest long-term (4-year) safety and functional data from this study.This study is funded by Sarepta Therapeutics.
- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
PK/PD Modeling to Inform Clinical Development of an Adeno-Associated Virus Gene Transfer Therapy for Duchenne Muscular Dystrophy (Petree Hall C) - May 3, 2023 - Abstract #ASGCT2023ASGCT_2294;
Relative specific force and western blot were not significantly correlated.For the first time, biodistribution, biomarker, and functional efficacy data were used to quantify and demonstrate PK/PD relationships for an adeno-associated virus (AAV)-based gene transfer therapy in a DMD animal model. The results continue to support the expected therapeutic benefit and clinical dose of delandistrogene moxeparvovec, an AAV-based gene transfer therapy.This study was funded by Sarepta Therapeutics, Inc.
- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
Evaluating Pharmacology and Efficacy of Delandistrogene Moxeparvovec in Young and Aged DMDMDX Rats (Board No. 1279) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1921;
Protein expression was broadly distributed across skeletal muscle, the diaphragm, and the heart.Taken together, these findings confirm expression in cardiac muscle, as expected, and support the myocardial efficacy and safety of delandistrogene moxeparvovec. Further evaluation of cardiac disease phenotypes at 12 and 24 weeks post-systemic delivery utilizing several indicators of cardiac function will also be presented.This study was funded by Sarepta Therapeutics.
- |||||||||| Exondys 51 (eteplirsen) / Sarepta Therap
Single-Cut Gene Editing Therapy for Duchenne Muscular Dystrophy via a Single AAV Vector (Board No. 951) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1673;
This unique DMD mouse model with the human genomic sequence allows in vivo assessment of clinically relevant gene editing strategies as well as other therapeutic approaches. Research on improving present antisense-based therapeutic strategies represents a significant step toward therapeutic translation of gene editing correction of patients with DMD.
- |||||||||| Exondys 51 (eteplirsen) / Sarepta Therap
Small Nuclear RNA-Mediated Exon 51 Skipping AAV9 Gene Therapy for the Treatment of Duchenne Muscular Dystrophy (Board No. 1198) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1402;
In summary, our novel designs allow for high-titer viral packaging of full-length AAV genomes carrying multiple highly expressing snRNA cassettes which we show to effectively skip DMD exon 51 and which can be rapidly deployed to therapeutically skip other DMD exons by switching antisense targeting sequences...3. Megan Waldrop, ASGCT 2022.
- |||||||||| Idefirix (imlifidase) / Hansa Biopharma, Sarepta Therap
Neutralizing Antibody Depletion with Imlifidase - A Potential Way to Enable AAV Based Gene Therapy in Seropositive Patients (Board No. 726) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1358;
All in all, antibody depletion with imlifidase could offer a simple and elegant way to enable gene therapy in seropositive patients with AAV antibodies and supports the rational for further clinical studies. The therapeutic effects of imlifidase established in various indications are thus being further evaluated in AAV based gene therapy in collaboration with gene therapy companies, including Sarepta Therapeutics and AskBio.*EU/EEA, UK and Switzerland
- |||||||||| Exondys 51 (eteplirsen) / Sarepta Therap
Precise Correction of Duchenne Muscular Dystrophy with Exon 51 Deletion by Adenine Base Editing-Induced Exon Skipping in a Humanized Mouse Model (Board No. 667) - Apr 21, 2023 - Abstract #ASGCT2023ASGCT_1357;
Here, we target the correction of the DMD exon51 deletion mutation by exon-skipping therapy of the exon50 which may therapeutically benefit DMD patients... This unique DMD mouse model with the human genomic sequence allows in vivo assessment of clinically relevant CRISPR ABE gene-editing strategies as well as other therapeutic approaches and represents a significant step toward therapeutic translation of adenine base editing for correction of patients with DMD or other genetic neuromuscular diseases.
- |||||||||| Idefirix (imlifidase) / Hansa Biopharma, Sarepta Therap
Enrollment closed: A Study of Imlifidase in Patients With Guillain-Barr (clinicaltrials.gov) - Apr 13, 2023
P2, N=30, Active, not recruiting,
This unique DMD mouse model with the human genomic sequence allows in vivo assessment of clinically relevant CRISPR ABE gene-editing strategies as well as other therapeutic approaches and represents a significant step toward therapeutic translation of adenine base editing for correction of patients with DMD or other genetic neuromuscular diseases. Recruiting --> Active, not recruiting
- |||||||||| Idefirix (imlifidase) / Hansa Biopharma, Sarepta Therap
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: An Long-term Follow-up Trial of Kidney Tx Patients Treated With Imlifidase or PE After an AMR (clinicaltrials.gov) - Apr 6, 2023
P=N/A, N=18, Terminated,
Recruiting --> Active, not recruiting N=30 --> 18 | Trial completion date: Apr 2025 --> Mar 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Mar 2023; This is an internal decision based on prioritisations and no safety issues have been raised during the trial.
- |||||||||| SRP-4055 / Sarepta Therap
Base Editing Correction of DMD in Human iPSC-Derived Cardiomyocytes and Dystrophic Mice (Board No. 505) - Apr 6, 2023 - Abstract #ASGCT2023ASGCT_602;
N=30 --> 18 | Trial completion date: Apr 2025 --> Mar 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2025 --> Mar 2023; This is an internal decision based on prioritisations and no safety issues have been raised during the trial. Co-transfection of ABE and a guide RNA (gRNA) targeting the splice acceptor led to efficient conversion of AG to GG (35.9%
- |||||||||| Vyondys 53 (golodirsen) / Sarepta Therap, Exondys 51 (eteplirsen) / Sarepta Therap, Viltepso (viltolarsen) / Nippon Shinyaku
Preclinical, Journal: In Vivo Evaluation of Exon 51 Skipping in hDMD/Dmd-null Mice. (Pubmed Central) - Apr 4, 2023
A solution to this issue is to use double mutant hDMD/Dmd-null mice, which only carry the human DMD sequence and are null for the mouse Dmd sequence. Here, we describe intramuscular and intravenous injections of an ASO to skip exon 51 in hDMD/Dmd-null mice, and the evaluation of its efficacy in vivo.
- |||||||||| Review, Journal: Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy. (Pubmed Central) - Mar 30, 2023
These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.
- |||||||||| Exondys 51 (eteplirsen) / Sarepta Therap
Journal: High-capacity adenovector delivery of forced CRISPR-Cas9 heterodimers fosters precise chromosomal deletions in human cells. (Pubmed Central) - Mar 21, 2023
Finally, all-in-one AdVP delivery of forced CRISPR-Cas9 heterodimers triggers robust DMD exon 51 splice site excision resulting in reading frame restoration and selection-free detection of dystrophin in muscle cells derived from Duchenne muscular dystrophy patients. In conclusion, AdVPs promote precise multiplexing genome editing through the integrated delivery of forced CRISPR-Cas9 heterodimer components, which, in comparison with split conventional CRISPR-Cas9 multiplexes, engage target sequences in a more coordinated fashion.
- |||||||||| scAAV1.tMCK.NTF3 / Sarepta Therap
Trial completion date, Trial primary completion date: Phase I/IIa Trial of scAAV1.tMCK.NTF3 for Treatment of CMT1A (clinicaltrials.gov) - Mar 14, 2023
P1/2, N=3, Suspended,
In conclusion, AdVPs promote precise multiplexing genome editing through the integrated delivery of forced CRISPR-Cas9 heterodimer components, which, in comparison with split conventional CRISPR-Cas9 multiplexes, engage target sequences in a more coordinated fashion. Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Mar 2023 --> Mar 2024
- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
PK/PD Modeling to Inform Clinical Development of an Adeno-associated Virus Gene Transfer Therapy for Duchenne Muscular Dystrophy (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_4400;
Conclusions For the first time, biodistribution, biomarker and functional efficacy data were used to quantify and demonstrate PK/PD relationships for an adeno-associated virus (AAV)-based gene transfer therapy in a DMD animal model. The results continue to support the expected therapeutic benefit and clinical dose of delandistrogene moxeparvovec, an AAV-based gene transfer therapy.
- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
One-year Data from ENDEAVOR, a Phase 1b Trial of Delandistrogene Moxeparvovec (SRP-9001) in Patients with Duchenne Muscular Dystrophy (DMD) (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_4398;
P1
There was a clinically meaningful and statistically significant difference in least-squares mean change from baseline to Year 1 in NSAA total score (?=3.2; P<0.0001), Time to Rise (?=-1.2; P<0.0001) and 10-meter Walk/Run (?=-1.0; P=0.0018) in treated patients relative to EC patients. Conclusions Cohort 1 data suggest the safety and efficacy profile of intended commercial process delandistrogene moxeparvovec material is consistent with that of clinical process material, with no new safety signals identified, and robust SRP-9001 dystrophin expression and positive functional benefit observed.
- |||||||||| delandistrogene moxeparvovec (SRP-9001) / Sarepta Therap, Roche
Evaluating Pharmacology and Efficacy of Delandistrogene Moxeparvovec in Young and Aged DMDmdx Rats (Both in-person and online) - Mar 12, 2023 - Abstract #AAN2023AAN_1800;
Conclusions Taken together, these findings confirm expression in cardiac muscle of rats, as expected, and support the potential myocardial efficacy and safety of delandistrogene moxeparvovec. Further results of cardiac disease phenotypes at 12 and 24 weeks post-systemic delivery utilizing several indicators of cardiac function will also be presented.
- |||||||||| Idefirix (imlifidase) / Hansa Biopharma, Sarepta Therap
IgG and IgM ABO antibodies detected by a novel bead-based assay fail to be discriminated by hemagglutination methods (Grand Georgian) - Mar 10, 2023 - Abstract #ITS2023ITS_37;
IgG Abs can contribute to non-AHG HA titres, despite the common assumption that only IgM Abs drive agglutination; each ABO titre includes an unpredictable range of ABO-Abs. This novel ABO-Ab detection method will allow better characterization of the relative roles of IgG vs IgM ABO-Abs in ABOi-transplantation, making it possible to manage immune risk with more isotype-specific tools such as imlifidase.
- |||||||||| Idefirix (imlifidase) / Hansa Biopharma, Sarepta Therap
Trial completion, Trial completion date: An Efficacy and Safety Study of Imlifidase in Treatment of Antibody-Mediated Rejection in Kidney Transplant Patients (clinicaltrials.gov) - Feb 28, 2023
P2, N=30, Completed,
This novel ABO-Ab detection method will allow better characterization of the relative roles of IgG vs IgM ABO-Abs in ABOi-transplantation, making it possible to manage immune risk with more isotype-specific tools such as imlifidase. Active, not recruiting --> Completed | Trial completion date: Mar 2023 --> Nov 2022
- |||||||||| ezutromid (SMT C1100) / Sarepta Therap
Development of next generation utrophin modulators for Duchenne muscular dystrophy: Learning from clinical setbacks (Room 138 (Indiana Convention Center)) - Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_11093;
Our demonstration through a series of target identification and validation studies that ezutromid binds to the arylhydrocarbon receptor (AhR) with high affinity, and antagonism of AhR by ezutromid leads to utrophin upregulation will be described, confirming AhR as a viable target for utrophin functional replacement therapies. The identification of new lead molecule AhR antagonists with better efficacy and improved properties compared to ezutromid will also be described, as will the implementation of an alternative screening strategy leading to the discovery of new molecules with a distinct mechanism of action to ezutromid.
- |||||||||| Vyondys 53 (golodirsen) / Sarepta Therap, Amondys 45 (casimersen) / Sarepta Therap
Enrollment closed: ESSENCE: Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - Jan 19, 2023
P3, N=229, Active, not recruiting,
The identification of new lead molecule AhR antagonists with better efficacy and improved properties compared to ezutromid will also be described, as will the implementation of an alternative screening strategy leading to the discovery of new molecules with a distinct mechanism of action to ezutromid. Recruiting --> Active, not recruiting
- |||||||||| SRP-4055 / Sarepta Therap
Journal: Correction of DMD in human iPSC-derived cardiomyocytes by base-editing-induced exon skipping. (Pubmed Central) - Jan 3, 2023
Transfection of ABE and a guide RNA (gRNA) targeting the splice acceptor led to efficient conversion of AG to GG (35.9% ± 5.7%) and enabled exon 55 skipping...Moreover, we designed gRNAs to target the splice sites of exons 6, 7, 8, 43, 44, 46, and 53 in the mutational hotspots and demonstrated their efficiency to induce exon skipping in iCMs. These results highlight the great promise of ABE-mediated exon skipping as a promising therapeutic approach for DMD.
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