Novartis spinal muscular dystrophy gene therapy Zolgensma is approved by the European Union!

Novartis gene therapy company AveXis recently announced that the European Commission (EC) has conditional approval of the gene therapy Zolgensma (onasemnogene abeparvovec) for the treatment of 5q spinal muscular dystrophy (SMA) patients(1) SMN1 has a double allele mutation, and clinically diagnosed as SMA-1 type 5q SMA patients; According to approved administration guidelines, the approval includes infants and young children weighing up to 21 kgZolgensma was approved by the U.SFDA in May 2019, becoming the world's first gene therapy to treat SMA5q-SMA is the most common type of SMA, accounting for about 95% of all SMA cases, this type of SMA is caused by the sMN1 (Motor Neuron Survival Protein 1) gene mutation on chromosome 5, hence the name 5q-SMAIn Europe, about 550-600 babies are born with SMA each yearSMA is a major burden on the European health system, with the cumulative cost of medical care per SMAestimated at between 2.5 and 4 million euros in the first 10 years aloneAccording to the Pediatric Neuromuscular Clinical Study (PNCR) SMA Natural History Study, almost all patients under the age of 5 weigh less than 21 kg, and some are under 21 kg at age 6, 7 and 8AveXis is planning a product launch that will allow treatment of patients weighing up to 21kg and is working with the EuropeanAuthority (EMA) to finalize the supply scheduleSMA is a rare genetic neuromuscular disease caused by a lack of functional SMN1 genesSMA can cause rapid and irreversible loss of motor neurons, affecting muscle function, including breathing, swallowing and basic movementSMN2 is a backup gene for SMN1, almost identical, the number of copies of SMN2 is negatively correlated with the severity of sma phenotypes, and patients with 2 copies of the SMN2 gene are likely to develop intoType SMA (also known as SMA-1 type); SMA is the number one genetic disease killer in infantunder 2 years of age, with SMA-1 being the most common type, accounting for about 60% of all cases Without treatment, more than 90 per cent of patients will die at age 2 or require permanent ventilation 　　Zolgensma is a revolutionary and highly innovative one-time gene therapy designed to address the genetic causes of SMA disease by replacing the function of the missing or ineffective SMN1 gene After a single intravenous infusion (IV) administration, Zolgensma introduced a functional copy of the SMN1 gene into the patient's cells, continuously expressing functional SMN proteins to prevent disease progression, thereby improving the quality of patient sesame in the long term Clinical studies have shown that Zolgensma single infusion therapy shows significant clinical benefits in patients with symptoms and symptoms, including extending event-free survival and achieving milestones not seen in the natural history of the disease 　　Dave Lennon, president of AveXis, said: "The EU's approval of Zolgensma is an important milestone for the SMA community, further underlining the great clinical value of Zolgensma as SMA's only gene therapy and offers new hope for patients affected by this rare but devastating disease Even in the current pandemic, Zolgensma has been established in France and Germany due to the urgent need for treatment of SMA In addition, we met with more than 100 stakeholder organizations in Europe to discuss our "Day One" acquisition program, which enables rapid access to Zolgensma treatment for SMA patients through customizable options running within the framework of local pricing and reimbursement "
the European Commission approved Zolgensma, based on the completed Phase I START trial and phase III STR1VE-US trial START and STR1VE-US were carried out in patients with symptomatic type 1 SMA who carried 1-2 copies of SMN2 backup genes and 2 copies of SMN2 backup genes, who were 6 months old at the time of administration, assessed the efficacy and safety of single-use intravenous infusion soma therapy Zolgensma showed :1 survival rate never seen in the natural history of the disease; Milestoneachievements within a month, including the ability to hold unsupported, are unachieved among untreated patients Patients in the START long-term follow-up trial are now 5 years old other supporting data include the medium-term results of the ongoing SPR1NT trial, an open label, single-arm Phase III trial, in patients genetically defined as SMN1 dual alleles, carrying 2-3 copies of SMN2 backup gene The patients assessed the efficacy and safety of a single one-time intravenous infusion of Zolgensma at the age of six weeks at the time of administration The mid-stage results from the SPR1NT trial showed significant milestones in the Zolgensma treatment, which strengthenthed importance of early intervention in SMA patients and required early diagnosis and treatment, including active support ivetherapy, to prevent irreversible loss of motor loss of neurons and disease progression In studies, the most common side effects of Zolgensma treatment were elevated liver enzymes and vomiting Patients may experience acute severe liver damage and elevated transaminase, and patients with congenital liver injury may have a higher risk Before infusion, the doctor should evaluate the liver function of all patients through clinical and laboratory examinations All patients should be treated with systemic corticosteroids before and after treatment, and liver function should continue to be monitored for at least 3 months after infusion 　　SMA is a motor neurone disease that causes muscle weakness and atrophy, which is an autosomal recessive genetic disease caused by a genetic defect that causes damage to the muscles below the patient's body, and the patient is characterized by general muscle atrophy, the body gradually loss of various motor functions, even breathing and swallowing SMA is the number one genetic disease killer in the infant population under 2 years of age, a relatively common "rare disease" with a prevalence rate of 1:6000-1:10,000 in newborns According to reports, the number of SMA patients in China is currently about 3-5 million so far, two drugs have been approved for SMA treatment In December 2016, spinraza, a drug developed by Yan Jian and partner Ionis, was approved as the world's first drug to treat SMA The drug is an antonymic nucleotide (ASO) that is delivered directly to the cerebrospinal fluid (CSF) around the spinal cord through intra-infusion injection, altering the splicing of the SMN2 pre-messenger RNA (pre-mRNA) and increasing the production of the full-length functional SMN protein In SMA patients, insufficient Levels of SMN protein sedlead the function of motor neurons in the spinal cord In clinical studies, Spinraza therapy significantly improved motor function in SMA patients In May 2019, Novartis gene therapy Zolgensma (onasemnogene abeparvec) was approved as the world's first gene therapy to treat SMA The drug can prevent the disease progression by continuously expressing SMN protein after single and disposable intravenous infusion, which can solve the underlying cause of SMA and hopefully improve the quality of life of patients in the long term , Roche is also developing an oral therapy, risdiplam, a motor neuron survival gene 2 (SMN2) shearing modifier for all types of SMA." The drug is under review by the FDA and is expected to be reviewed in August If approved, risdiplam will be the first oral drug to treat all three types of SMA in the Chinese market, Spinraza was approved at the end of February 2019 for the treatment of patients with 5q spinal muscular dystrophy (5q-SMA) This approval makes Spinraza the first drug to be used to treat SMA in the Chinese market original origin: AveXis receives eCapproval and activates "Day One" access program for Zolgensma, the only gene therapy for spinal atrophy (SMA)