by: Parent Project Muscular Dystrophy
Solid Biosciences has provided a safety and efficacy update on the ongoing IGNITE DMD phase I/II clinical study of SGT-001 microdystrophin gene therapy in patients with Duchenne.
Upcoming Webinar:
Join PPMD and Solid tomorrow, March 16 at 1 PM EDT as we host a community webinar to discuss this update.
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Letter to the Duchenne Community: Data and IGNITE DMD Clinical Trial UpdateDear Duchenne Community,
We are pleased to share an update regarding the safety and efficacy data from our ongoing IGNITE DMD phase I/II clinical trial, as announced in the press release issued this afternoon. Additionally, we are excited to announce that we have resumed safe dosing at the 2E14 vg/kg dose, and that this patient experienced mild to moderate adverse events all of which have fully resolved. We are encouraged with the improved safety profile of SGT-001 under our previously reported amended protocol and second-generation manufacturing process, both of which were designed to enhance patient safety.
The data reported were collected from the first six patients dosed in IGNITE DMD twelve to twenty-four months after treatment and include data from three patients dosed at the low dose (5E13vg/kg) and three patients dosed at the high dose (2E14 vg/kg). Data from the delayed treatment cohort, analyzed as an untreated control cohort, were evaluated alongside representative natural history data. The six patients ranged in age from five to 14-years-old at time of dosing.
We are looking forward to hosting a webinar with Parent Project Muscular Dystrophy tomorrow, Tuesday, March 16, at 1pm ET to review the data included below in more detail and take questions from the community.
Functional Data
- Among patients in the low and high dose cohorts, North Star Ambulatory Assessment (NSAA) scores at 1 year suggest benefit after treatment as compared to trajectories typically observed in natural history data. Natural history analyses suggest that patients similarly aged to those enrolled in IGNITE DMD would normally be expected to have either plateaued in gains or exhibit a 3 to 3.7-point decline year over year. Patients in the untreated control cohort exhibited a mean decline of 4.0 points from baseline to 1 year, while patients in the low dose cohort exhibited a mean improvement of 1.0 point over the same period of time. Patients in the high dose exhibited a mean improvement of 0.3 as compared to their baseline values.
- Mean increase in the 6-Minute Walk test (6MWT) distance was above the generally accepted minimally clinically important difference (MCID) of 30 meters in both the low and high dose cohorts after treatment. While patients in the untreated control cohort exhibited a decline of 8.5 meters from baseline to 1 year, patients in the low dose cohort exhibited a mean improvement of 37 meters and patients in the high dose cohort exhibited an improvement of 49.7 meters over the same 12 month period.
- With respect to spirometry testing of pulmonary function, the majority of patients in both dose groups exhibited improved forced vital capacity (% predicted FVC) at one year when declines in pulmonary function would otherwise be typically observed in patients with Duchenne. From baseline to 1 year, patients in the untreated control cohort exhibited a mean decline of 10.7% on an absolute basis, while patients in the low dose and high dose cohorts exhibited a mean improvement of 3.9% and 16.7%, respectively, over the same period.
Biomarker Data
- As previously reported, biopsies of skeletal muscle three months after a single infusion of SGT-001 at a dose of 2E14vg/kg demonstrated widespread distribution of microdystrophin-positive muscle fibers with co-localization of nNOS and β-sarcoglycan in the muscles of these patients.
- Creatine kinase (CK) assessments of the six patients provide potential physiological evidence of a positive or stabilizing effect after one year of treatment with a single high dose infusion of SGT-001. An average sustained CK decline of approximately 50% in patients in the high dose cohort was observed.
Patient Reported Outcome (PROMs) Data
Patient reported outcomes measures taken after one year of treatment revealed a trend towards dose-ordered improvements in motor function subscales and fatigability assessments, providing real-world evidence to support the clinical and biomarker findings of varying degrees of benefit in low and high dose patients.
- Meaningful improvements in the Pediatric Outcomes Data Collection Instrument (PODCI), a validated PROM that contains questions to assess how caregivers and children evaluate the child’s ability to walk, stand, and perform activities of daily living, as well as recreational activities. Motor function scores reflect the gains seen in 6MWT and benefit of NSAA observed in all dosed patients.
- Semi-structured, qualitative interviews conducted by Modus Outcomes Ltd with patients and caregivers about the impact of Duchenne on functioning demonstrated overall improvement in functional activity and school-related impacts (e.g., lower limb mobility, keeping up with peers, climbing stairs, sports) in low- and high-dose cohorts, with subjective decreased fatigability in all patients of both treatment cohorts.
The totality of data collected, and the re-initiation of safe dosing support the continued enrollment of patients into the IGNITE DMD study. We encourage you to regularly visit clinicaltrials.gov (NCT03368742) for updates as they become available. If you have any questions, please feel free to contact us directly at Community@solidbio.com.
We look forward to speaking with the community tomorrow afternoon during the webinar hosted by PPMD.
#TogetherWeAreSolid
Sincerely,
Your Solid Biosciences Team
Read the Press Release from Solid:
Solid Biosciences Reports Efficacy and Safety Data from the Ongoing IGNITE DMD Clinical Trial and Resumption of Patient Dosing in the 2E14 vg/kg Cohort
– Interim data from six patients provide evidence of a potential benefit of SGT-001 in functional endpoints of North Star Ambulatory Assessments (NSAA), 6-minute walk test (6MWT), pulmonary function tests (PFTs), and clinically validated patient reported outcome measures (PROMs) –
– Patient 7, safely dosed with SGT-001, experienced transient and manageable adverse events, none of which were serious; six patients previously dosed showed no new drug-related safety findings 17-37 months post dosing; screening and enrollment of patients into IGNITE DMD continue –
– Presentations to follow at the 2021 Muscular Dystrophy Association (MDA) Virtual Clinical & Scientific Conference –
– Company to host conference call and webcast today at 4:30 PM ET to discuss clinical data and financial results –
CAMBRIDGE, Mass., March 15, 2021 (GLOBE NEWSWIRE) — Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company focused on advancing meaningful therapies for Duchenne muscular dystrophy (Duchenne), today reported encouraging interim functional (NSAA, 6MWT and PFTs) and biomarker data, and patient reported outcome measures (PROMs) from six patients after treatment in the ongoing IGNITE DMD Phase I/II clinical trial of its lead gene therapy candidate, SGT-001. The Company also announced that patient 7 in IGNITE DMD was safely dosed, with transient and manageable adverse events, none of which were serious. Patient 7 was the first patient dosed in IGNITE DMD under a previously reported clinical protocol amendment and using SGT-001 manufactured with its second-generation process. Additionally, the six patients previously dosed showed no new drug-related safety findings, 17-37 months post dosing. The totality of data collected, and the re-initiation of dosing, support the continued enrollment of patients into the IGNITE DMD study.
These data will also be presented in an oral session and at a company-sponsored symposium at the 2021 MDA Virtual Clinical & Scientific Conference on Thursday, March 18.
“The totality of the functional and biomarker data, as well as the patient reported outcome measures reported today suggest that SGT-001 may provide benefit to patients with Duchenne, a serious disease for which there is no cure,” said Barry Byrne, M.D., Ph.D., Associate Chair of Pediatrics and Director of the Powell Gene Therapy Center at the University of Florida, and Principal Investigator of the IGNITE DMD clinical study. “I am particularly encouraged by these early data when compared with the natural history of this disease. I look forward to the continued enrollment in IGNITE DMD and evaluating the data as the study progresses.”
“We are encouraged with the successful resumption of dosing in the IGNITE DMD trial under our amended clinical protocol and using SGT-001 manufactured with a second-generation process. The safe dosing of the seventh patient gives us increased confidence in our dosing strategy as we move forward with clinical development in the IGNITE DMD clinical trial. We are grateful to this patient and his family, and to all those who choose to participate in clinical trials,” said Ilan Ganot, Chief Executive Officer, President and Co-Founder of Solid Biosciences. “We look forward to continuing to dose patients and reporting clinical outcomes from additional patients in the second half of 2021.”
IGNITE DMD Data
The data reported were collected from the first six patients dosed in IGNITE DMD 12 to 24 months after treatment and include data from three patients dosed at the low dose (5E13 vg/kg) and three patients dosed at the high dose (2E14 vg/kg). Data from the delayed treatment cohort, analyzed as an untreated control cohort, were evaluated alongside representative natural history data. The six patients ranged in age from five to 14-years-old at baseline. These data have been previously shared with FDA, as well with members of the IGNITE DMD Data Safety Monitoring Board and clinical consultants.Functional Data
- Among patients in the low and high dose cohorts, North Star Ambulatory Assessment (NSAA) scores at one year suggest benefit after treatment as compared to trajectories typically observed in natural history data. Natural history analyses suggest that patients similarly aged to those enrolled in IGNITE DMD would normally be expected to exhibit year-over-year disease progression ranging from a plateau in gains to a 3 to 3.7-point decline. Patients in the untreated control cohort exhibited a mean decline of 4.0 points from baseline to 1 year, while patients in the low-dose cohort exhibited a mean improvement of 1.0 point over the same period of time. Patients in the high-dose cohort exhibited a mean improvement of 0.3 points as compared to their baseline values.
- Mean increase in the 6-Minute Walk Test (6MWT) distance was above the generally accepted minimally clinically important difference (MCID) of 30 meters in both the low- and high-dose cohorts after treatment. While patients in the untreated control cohort exhibited a decline of 8.5 meters from baseline to one year, patients in the low-dose cohort exhibited a mean improvement of 37 meters and patients in the high-dose cohort exhibited an improvement of 49.7 meters over the same period.
- With respect to pulmonary function tests (PFTs), the majority of patients in both dose groups exhibited improved forced vital capacity (% predicted FVC) at one year when declines in pulmonary function would otherwise be typically observed in patients with Duchenne. From baseline to one year, patients in the untreated control cohort exhibited a mean decline of 10.7% on an absolute basis, while patients in the low-dose and high-dose cohorts exhibited a mean improvement of 3.9% and 16.7%, respectively, over the same period.
Biomarker Data
- As previously reported, biopsies of skeletal muscle three months after a single infusion of SGT-001 at a dose of 2E14vg/kg demonstrated widespread distribution of microdystrophin-positive muscle fibers with co-localization of neuronal nitric oxide synthase (nNOS) and β-sarcoglycan in the muscles of these patients.
- Creatine kinase (CK) assessments of the six patients provide potential physiological evidence of a positive or stabilizing effect after one year of treatment with a single high-dose infusion of SGT-001. An average sustained CK decline of approximately 50% in patients in the high-dose cohort was observed. In the low-dose cohort, an average CK increase of approximately 166% was observed, and in the control group an average CK increase of approximately 17% was observed.
Patient Reported Outcome Measures (PROMs) Data
Patient reported outcome measures taken after one year of treatment revealed a trend towards dose-ordered improvements in motor function subscales and fatigability assessments, providing real-world evidence to support the clinical and biomarker findings of varying degrees of benefit to patients in the low- and high- dose cohorts.
- Meaningful improvements were demonstrated in the Pediatric Outcomes Data Collection Instrument (PODCI), a validated PROM that contains questions to assess how caregivers and children evaluate the child’s ability to walk, stand, and perform activities of daily living, as well as recreational activities. Motor function scores reflect the gains seen in 6MWT and benefit of NSAA observed in all dosed patients.
- Semi-structured, qualitative interviews conducted by Modus Outcomes Ltd with patients and caregivers about the impact of Duchenne on functioning demonstrated overall improvement in functional activity and school-related impacts (e.g., lower limb mobility, keeping up with peers, climbing stairs, sports) in low- and high-dose cohorts, with subjective decreased fatigability in all patients of both treatment cohorts.
As previously reported, three of the first six patients dosed prior to the protocol amendments introduced in 2020 developed four serious adverse events (SAEs). All prior SAEs have fully resolved, and no new drug-related safety findings have been identified with post-dosing follow up of 17-37 months. Additionally, as reported today, with resumption of dosing in IGNITE DMD, patient 7 was dosed safely with mild to moderate adverse events, all of which have fully resolved. The resumption of dosing was under an amended clinical protocol and using SGT-001 manufactured with an improved process, both of which are designed to enhance patient safety.
Data Presentations at MDA
Dr. Byrne will present the IGNITE DMD efficacy and safety data during a virtual oral session at the MDA conference on Thursday, March 18, 2021 at 4:00 PM ET. Also, on March 18, the PROM data will be presented during a Company-sponsored lunch symposium at 12:00 p.m. ET. Registration for the MDA conference is required to attend the oral presentation and the lunch symposium. Registration information is available at: https://mdavirtualconference.org/en/registration.
MDA Presentation Details
Presentation Title: IGNITE-DMD: Phase I/II Ascending Dose Study of Single IV Infusion of SGT-001 Microdystrophin Gene Therapy for DMD: One Year Efficacy and Safety Results
Presentation Date: Thursday, March 18, 2021, 4:00 PM ET
Symposium Details
Also, on March 18, Solid Biosciences will sponsor a symposium, “Real World Outcome Measures in Duchenne Muscular Dystrophy: Current and Novel Assessments of Meaningful Patient Benefit” at 12 PM ET. The symposium will feature:
- Valeria Ricotti, MD, Co-Founder, Executive Vice-President & Chief Medical Officer at DiNAQOR, Honorary Clinical Lecturer, Biomedical Research Centre, UCL GOS Institute of Child Health
- Chad R. Heatwole, MD, MS-CI, Professor of Neurology, Associate Director of the Center for Health + Technology (CHeT) and CHeT Outcomes Division Director at the University of Rochester Medical Center
- Craig M. McDonald, MD, Professor and Chair of the Department of Physical Medicine and Rehabilitation at the University of California, Davis
