The first oral drug for spinal muscular atrophy (SMA)! The key clinical research of risdiplam in the treatment of SMA type 1 was successful!

January 24, 2020 / BIOON / -- Roche, a Swiss pharmaceutical giant, recently released the positive results of the second part of the key firefish study (nct02913482) to evaluate risdiplam in the treatment of spinal muscular atrophy type 1 (SMA) infants Risdiplam is a splicing modifier of motor neuron survival gene 2 (SMN2), which has been developed for the treatment of all types of SMA Currently, the drug is under priority review by the US FDA, which will make a review decision in May this year If approved, risdiplam will be the first oral drug to treat all three types of SMA As part of a partnership with SMA foundation and PTC therapeutics, Roche led risdiplam's clinical development project If approved, Roche will be responsible for the commercialization of risdiplam in the United States Firefish is an open label, multicenter phase II / III study that is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of risdiplam in 1-7 months old infants with type 1 SMA The study consisted of two parts, exploratory dose discovery (Part I, n = 21) and confirmatory (Part II, n = 41) In the second part, the patients will be treated with risdiplam orally for 24 months at the dose selected in the first part, and the main outcome index is the proportion of infants sitting without support for at least 5 seconds after 12 months of treatment, which is evaluated by the total exercise scale of Bailey infant development scale (bsid-iii) The results showed that the study reached the primary end point: risdiplam treatment of type 1 SMA infants showed statistically and medically significant improvement in motor milestones In this study, the security of risdiplam is consistent with its known security profile, and no new security signal is found Data from the study will be released at the upcoming medical conference So far, more than 400 patients have been treated with risdiplam in all the studies, and no safety finding related to treatment leading to drug withdrawal has occurred in any of the studies Levi Garraway, MD, chief medical officer of Roche and head of global product development, said: "this large-scale global trial confirms the efficacy of risdiplam in advanced and refractory populations, including many infants whose disease has progressed significantly before treatment We are very encouraged by these results, and we look forward to sharing them with regulators We also thank the entire SMA community for their continued cooperation " Risdiplam chemical structure (picture source: medchemexpress CN) risdiplam is an oral liquid, motor neuron survival gene 2 (SMN2) splicing modifier designed to continuously increase and maintain the level of SMN protein in the central nervous system and peripheral tissues More and more clinical evidences show that SMA is a multisystem disease The loss of SMA protein may affect many tissues and cells outside the central nervous system Risdiplam showed systemic distribution after oral administration, and increased the level of SMN protein in central nervous system and peripheral tissues continuously It has been shown that risdiplam can improve the motor function of type 1, type 2 and type 3 SMA patients Risdiplam is expected to be the first oral drug to treat all three types of SMA In November 2019, FDA accepted risdiplam's new drug application (NDA) for SMA treatment and granted priority review The target date of PDUFA is May 24, 2020 Previously, FDA has granted risdiplam orphan drug qualification and fast track qualification Risdiplam is an oral liquid preparation that, if approved, will be the first drug to be available at home for SMA patients Risdiplam NDA contains 12-month data from the first part of dose discovery from the key firefish study and the sunfish study, as well as data from the second part of validation of the sunfish study Sunfish is a two-part, double-blind, placebo-controlled, critical clinical trial in type 2 or 3 SMA children and young adults (2-25 years old) The first part defines the dose of the confirmatory second part, and the exploratory end point is to evaluate the efficacy The second part is a large placebo-controlled trial to evaluate risdiplam in the treatment of type 2 or type 3 SMA patients The second part of the data released in November 2019 showed that the study reached the main end point of the change of mfm-32 score relative to the baseline: after one year of treatment, risdiplam treated patients showed significant improvement in motor function compared with placebo group In addition to the studies included in the NDA, risdiplam is conducting research in a wide range of SMA clinical trials involving patients from newborns to 60 years old, as well as those who have previously received SMA therapy At present, Roche is carrying out four global multicenter clinical studies (sunfish [nct02908685], firefish [nct02913482], jewelfish [nct03032172], Rainbowfish [nct03779334]) to evaluate the efficacy and safety of risdiplam in the treatment of all types of SMA (type 1, type 2, type 3) and pre symptom SMA SMA is a kind of motor neuron disease that can lead to muscle weakness and atrophy This disease is an autosomal recessive genetic disease caused by gene defects, which will damage the muscles around the patient The main symptoms of the patient are muscle atrophy and weakness, and the body gradually loses all kinds of motor functions, even breathing and swallowing SMA is the number one killer of genetic disease in infants under 2 years old It is a relatively common "rare disease" with a prevalence of 1:6000-1:10000 in newborns According to relevant reports, the number of SMA patients in China is about 30000-50000 at present In December 2016, spinraza (nusinersen), a drug developed by Bojian and its partner Ionis, was approved as the first drug to treat SMA in the world The drug is an antisense oligonucleotide (ASO), which is injected intrathecally to deliver the drug directly to the CSF around the spinal cord, change the splicing of SMN2 pre mRNA, and increase the production of full-functional SMN protein In SMA patients, the lack of SMN protein results in the degeneration of spinal motor neuron function In clinical studies, spinraza treatment significantly improved the motor function of SMA patients In May 2019, zolgensma (onasemnogene abeparvovec), a gene therapy from Novartis, was approved as the first gene therapy for SMA in the world The drug can prevent the progression of disease by continuously expressing SMN protein after a single and one-off intravenous infusion It can solve the root cause of SMA and is expected to improve the quality of life of patients for a long time In the Chinese market, spinraza was approved in late February 2019 for the treatment of 5q spinal muscular atrophy (5q SMA) patients This approval makes spinraza the first drug to treat SMA in the Chinese market 5q SMA is the most common type of SMA, accounting for 95% of all SMA cases This type of SMA is caused by the mutation of SMN1 (motor neuron survival protein 1) gene on chromosome 5, so it is named 5q SMA Source of original text: Roche's risdiplam meets primary endpoint in pivotal firefish trial in strengths with type 1 spiral muscular topology