Novartis Highlights Transformative Efficacy of Zolgensma, the First and Only Gene Therapy for Spinal Muscular Atrophy, in Both Presymptomatic and Symptomatic Children

SMA Boy (Image from: drpgx.com)

June 19, 2021 News /BioValleyBIOON/ --Novartis(Novartis) recently announced new data reinforcing the transformative benefits of Zolgensma (onasemnogene abeparvovec) as an important one-time therapy and the only gene therapy for spinal muscular atrophy (SMA). From the completed Phase 3 SPR1NTClinical TrialsNew data from the dual-copy queue,Demonstrated that treated presymptomatic SMA children achieved age-appropriate developmental milestones without any respiratory or nutritional support., and no serious treatment-related adverse events were reported. Data from the completed Phase 3 STR1VE-EU trial indicate that,Following treatment with Zolgensma, patients experienced rapid improvement in motor function, with the majority achieving motor milestones not observed in the natural history of type 1 SMA.。Safety was consistent with previously reported data. These data will be presented online at the 2021 European Academy of Neurology (EAN)Conferencepublished on.

Spinal muscular atrophy (SMA) is a rare`Genetics`disease that causes progressive muscle weakness, paralysis, and even death. Without treatment, most pediatric patients with severe SMA will either become permanently dependent on mechanical ventilation for survival or ultimately die by the age of two.

Zolgensma is, to date, approved for the treatment of patients with SMA (including inDiagnosisthe first and only gene therapy for (patients who have not yet developed symptoms).In May 2019, Zolgensma received U.S.FDAApproved for the treatment of pediatric patients under 2 years of age with spinal muscular atrophy (SMA) who have biallelic mutations in the survival motor neuron 1 (SMN1) gene. Zolgensma addresses the underlying cause of SMA by providing a functional copy of the human SMN gene toHeredityFundamentally, sustained SMN protein expression from a single intravenous injection alone is sufficient to halt disease progression.

Data presented at the EAN Congress indicate that the treatment data for Zolgensma stand in stark contrast to the natural history of type 1 SMA, which causes progressive and irreversible loss of motor function. Without treatment, patients typically die or require permanent ventilation by age 2. In the SPR1NT two-copy cohort,All presymptomatic children with SMA who received treatment (100%) achieved the primary endpoints of event-free survival, independence from respiratory and nutritional support, and sitting independently for ≥30 seconds, including 11/14 (79%) who achieved this milestone within the World Health Organization (WHO) normal developmental window. The majority of patients were able to stand independently (11/14, 79%) and walk independently (9/14, 64%), with most (7 and 5 patients, respectively) achieving these milestones within the normal developmental window.

In the STR1VE-EU trialAmong symptomatic children with type 1 SMA who received treatment, including those with more severe disease at baseline, the majority (27/32, 82%) achieved developmental motor milestones not observed in the natural history of type 1 SMA, including 16 children (49%) who sat unsupported for ≥30 seconds.

NovartisGene therapyDr. Shephard Mpofu, Chief Medical Officer and Senior Vice President, stated: “With over 1,200 children now treated, the data presented at the EAN Congress further reinforce the life-changing benefits of the one-time gene therapy Zolgensma. When administered prior to symptom onset, not only did all patients survive, but they also thrived—breathing and feeding independently, with many standing and walking on their own. Without treatment, these neonatal patients would have developed severe Type 1 SMA, a devastating and progressive disease that deprives children of the ability to speak, eat, sit, or even breathe. In light of this, the results from the SPR1NT trial are truly remarkable.”

Eugenio Mercuri, MD, Department of Pediatric Neurology, Catholic University of the Sacred Heart, Rome, Italy, stated: “The STR1VE-EU trial enrolled SMA patients with more severe disease at baseline, yet the study demonstrated that symptomatic children with Type 1 SMA achieved consistent and significant therapeutic benefits. This is a remarkable outcome that adds to the substantial clinical evidence for Zolgensma, demonstrating that it is highly effective even in patients with more severe disease and maintains a consistent safety profile.” (Bioon.com)

Spinal muscular atrophy (SMA) is a rare inherited neuromuscular disorder caused by a deficiency of functional SMN1 genes. SMA results in the rapid and irreversible loss of motor neurons, impairing muscle function, including respiration, swallowing, and basic movement. SMN2 serves as a near-identical backup copy of SMN1. The SMN2 copy number is inversely correlated with the severity of the SMA phenotype: patients with two SMN2 gene copies are likely to develop infantile-onset SMA (also known as type 1 SMA), whereas those with three or four SMN2 gene copies may develop later-onset SMA (types 2 and 3 SMA). SMA is the leading ... among infants and young children under the age of 2.Hereditydisease killer, among which Type 1 SMA is the most common type, accounting for approximately 60% of all cases. Without treatment, over 90% of patients will die or require permanent mechanical ventilation by the age of 2.

Zolgensma is a revolutionary and highly innovative one-time gene therapy designed to address the genetic root cause of SMA by replacing the function of missing or nonfunctional SMN1 genes.Following a single intravenous (IV) infusion, Zolgensma delivers a functional copy of the SMN1 gene into the patient's cells, leading to sustained expression of functional SMN protein to halt disease progression, thereby improving patients' quality of life over the long term. Clinical studies have shown that in symptomatic and presymptomatic patients with SMA, treatment with a single infusion of Zolgensma provides clinically meaningful therapeutic benefits, including prolonged event-free survival and the achievement of motor milestones not observed in the natural history of the disease.

To date, three drugs have been approved for the treatment of SMA. In December 2016, Spinraza (nusinersen), developed by Biogen and its partner Ionis, was approved, becoming the world's first therapy for SMA. This medication is an antisense oligonucleotide (ASO) administered via intrathecal injection, delivering the drug directly into the cerebrospinal fluid (CSF) surrounding the spinal cord. It modulates the splicing of SMN2 pre-messenger RNA (pre-mRNA) to increase the production of full-length, functional SMN protein. In patients with SMA, deficient levels of SMN protein lead to the degeneration of spinal motor neurons. Clinical studies have demonstrated that Spinraza treatment significantly improves motor function in individuals with SMA.

May 2019,NovartisThe gene therapy Zolgensma (onasemnogene abeparvovec) has been approved, becoming the world's first gene therapy for the treatment of SMA. Administered as a single, one-time intravenous infusion, the drug enables sustained expression of the SMN protein to halt disease progression, addresses the underlying cause of SMA, and holds the potential to improve patients' quality of life in the long term.

In August 2020, Roche’s Evrysdi (risdiplam) was approved, becoming the first oral therapy for the treatment of SMA. The drug is a survival motor neuron 2 (SMN2) mRNA splicing modifier that treats SMA by increasing the production of survival motor neuron (SMN) protein. Evrysdi is an oral liquid formulation indicated for the treatment of infant, pediatric, adolescent, and adult patients aged ≥2 months with all types (Type 1, Type 2, Type 3) of SMA.

In China, February 2019,Biogen Spinraza (Nusinersen Sodium Injection) ReceivesApproved by the National Medical Products Administration (NMPA), it is indicated for the treatment of patients with 5q spinal muscular atrophy (5q-SMA). 5q-SMA accounts for approximately 95% of all SMA cases. This approval makes Spinraza the first therapeutic agent for SMA in the Chinese market. Most recently (June 16, 2021),Roche Evrysdi (Brand Name: Aimanxin, Risdiplam Powder for Oral Solution)Approved by the National Medical Products Administration (NMPA) for the treatment of patients with SMA aged 2 months and older. Evrysdi is the first oral disease-modifying therapy (DMT) approved in China for the treatment of SMA, providing a novel therapeutic option for SMA patients and their families in China. (Bioon.com)

Original Source:New Zolgensma data demonstrate age-appropriate development when used presymptomatically and rapid, clinically meaningful efficacy in symptomatic children, even those with severe SMA at baseline