Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by loss of motorneurons in the spinal cord leading to progressive muscle atrophy and weakness. The disorder is caused by a homozygous deletion of the SMN1 gene resulting in deficiency of the SMN (survival of motor neuron) protein. Patients with the most severe form of the disease, type I SMA, present between 0 and 6 months with hypotonia and muscle weakness. If untreated, they develop respiratory and swallowing problems and most children die before the age of 2 years. Patients with type 2 SMA present between 6 and 18 months. They do achieve independent sitting, but never obtain the ability to walk and suffer from severe respiratory and orthopaedic complications. Type 3 SMA patients present later, after 18 months. These patients can walk, but they lose ambulation later on in life.
A Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam in Patients with Spinal Muscular Atrophy (F. Hoffmann-La Roche Ltd)
Principal Investigator: Prof. Liesbeth De Waele
Jewelfish: An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of RO7034067 in Adult and Pediatric Patients With Spinal Muscular Atrophy.
The Jewelfish study is studying the safety, tolerance and pharmacokinetics/dynamics of risdiplam in patients with SMA type 2 and 3 who were previously treated with another product (branaplam, nusinersen, onasemnogene abeparvovec, olesoxime). Risdiplam increases via the SMN2 gene the expression of the SMN protein that should prevent the death of motor neurons in the spinal cord.
Risdiplam needs to be taken daily by mouth.
A study to evaluate the safety, tolerability and efficacy of gene replacement therapy with intravenous OAV101 (AVXS-101) in pediatric patients with spinal muscular atrophy (SMA) (Novartis)
Principal Investigator: Prof. Liesbeth De Waele
COAV101A12306 - SMART: A Phase IIIb, open-label, single-arm, multicenter study to evaluate the safety, tolerability and efficacy of gene replacement therapy with intravenous OAV101 (AVXS-101) in pediatric patients with spinal muscular atrophy (SMA)
COAV101A12308 - SPECTRUM: Long-term follow-up of patients with spinal muscular atrophy Treated with OAV101 IT or OAV101 IV in Clinical Trials
The COAV101A12306 - SMART study examines the efficacy and safety of OAV101 in patients with Spinal Muscular Atrophy (SMA) weighing 8.5 to 21 kg. OAV101 is a genetically modified organism (GMO) consisting of a viral vector derived from the adeno-associated virus (AAV) with a copy of the human SMN1 gene. Single intravenous administration of this vector would provide stable production of the SMN1 protein, improving the condition of SMA patients.
The COAV101A12308 - SPECTRUM study is a long-term follow-up for patients who participated in one of the COAV studies, for example, COAV101A12306. This study will evaluate the long-term safety and efficacy of OAV101.
A study to evaluate the safety and efficacy of gene replacement therapy with intrathecally OAV101 (AVXS-101) in pediatric patients with spinal muscular atrophy (Novartis)
Principal investigator: Prof. Dr. Liesbeth De Waele
COAV101B12302 - STRENGTH: Phase IIIb, open-label, single-arm, multi-center study to evaluate the safety and efficacy of OAV101 administered intrathecally (1.2 x 1014 vector genomes) to participants 2 to 12 years of age with spinal muscular atrophy (SMA) who have previously been treated with nusinersen or risdiplam
COAV101A12308 - SPECTRUM: Long-term follow-up of patients with spinal muscular atrophy Treated with OAV101 IT or OAV101 IV in Clinical Trials
This study examines the efficacy and safety of OAV101 in patients with Spinal Muscular Atrophy (SMA) aged 2 to 12 years at time of screening. OAV101 is a genetically modified organism (GMO) consisting of a viral vector derived from the adeno-associated virus (AAV) with a copy of the human SMN1 gene. Single intrathecally administration of this vector would provide stable production of the SMN1 protein, improving the condition of SMA patients.
The COAV101A12308 study is long-term follow-up for patients who participated in one of the COAV studies, for example, COAV101B12302. This study will evaluate the long-term safety and efficacy of OAV101.
A Treatment Trial to Evaluate the Efficacy and Safety of Apitegromab in Patients with Later-Onset Spinal Muscular Atrophy Who Are Being Treated with Nusinersen or Risdiplam (Scholar Rock)
Principal investigator: Prof. Dr. Liesbeth De Waele
SRK-015-003 SAPPHIRE: Phase 3, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Apitegromab (SRK-015) in Patients with Later-Onset Spinal Muscular Atrophy Receiving Background Nusinersen or Risdiplam Therapy
The SAPPHIRE study is studying the efficacy and safety of Apitegromab (SRK-015) in non-ambulant patients with type 2 or 3 Spinal Muscular Atrophy (SMA) aged 2 to 21 years. Apitegromab is a myostatin inhibitor. Myostatin is a protein that inhibits muscle growth. Apitegromab inhibits this protein, resulting in increased muscle mass and possibly increased muscle force.
SRK-015 is administered intravenously monthly in combination with risdiplam or nusinersen.
A study to evaluate the efficacy and safety of Taldefgrobep Alfa in ambulatory and non-ambulatory participants with spinal muscular atrophy (Biohaven Pharmaceuticals)
Principal investigator: Prof. Dr. Liesbeth De Waele
RESILIENT: A randomized, double-blind, placebo-controlled, study to evaluate the efficacy and safety of taldefgrobep alfa in ambulatory and non-ambulatory participants with Spinal muscular atrophy (SMA) with open-label extension
The RESILIENT study is studying the efficacy and safety of Taldefgrobep alfa in patients with Spinal muscular atrophy (SMA) aged 4 to 21 years. Taldefgrobep alfa is a myostatin inhibitor administered in combination with risdiplam, nusinersen or onasemnogene abeparvovec. Myostatin is a protein that inhibits muscle growth. Taldegrobep alfa inhibits this protein, resulting in increased muscle mass and possibly increased muscle force.
Taldefgrobep alfa is administered subcutaneously weekly.