Spinal muscular atrophy (SMA) is the first oral drug! Risdiplam, Roche's splicing modifier, has entered the priority review in the United States!

November 26, 2019 / biourn / -- Roche recently announced that the U.S Food and Drug Administration (FDA) has accepted risdiplam's new drug application (NDA) and granted priority review The drug is a splicing modifier of motor neuron survival gene 2 (SMN2) for the treatment of spinal muscular atrophy (SMA) FDA has designated the target date of PDUFA as 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 As part of a partnership with SMA foundation and PTC therapeutics, Roche led risdiplam's clinical development project This NDA acceptance also triggered Roche's milestone payment of $15 million to partner PTC If approved, Roche will be responsible for the commercialization of risdiplam in the United States Risdiplam NDA contains 12-month data from the first part of dose discovery in the firefish and sunfish key studies, as well as data from the second part of validation in the sunfish study Firefish is an open label, two-part critical clinical trial The first part is a dose increasing study in type 1 SMA infants 21 infants aged 1-7 months were enrolled in the study The main purpose is to evaluate the safety of risdiplam in infants and determine the dose of the second part The exploratory end point is to evaluate the efficacy The second part is a key and single arm test 41 infants with type 1 SMA are being evaluated for risdiplam treatment for 24 months, and then Is an open label extension period 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 recently published data shows 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 So far, none of the clinical trials evaluating risdiplam has found treatment-related safety findings leading to discontinuation of the study The security of risdiplam is consistent with the known security, and no new security signal is found The results will be announced at the upcoming medical conference Levi Garraway, MD, chief medical officer of Roche, director of global product development, said: "the firefish and sunfish trials are designed to represent the real population of SMA patients, including many patients who were previously underrepresented in clinical trials We look forward to working closely with FDA to explore broad access to risdiplam for all patients in the SMA community who may benefit " 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 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 Spinraza: the world's first SMA treatment drug, China was approved in February this year 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 this year, zolgensma (onasemnogene abeparvovec), a gene therapy from Novartis, was approved as the world's first gene therapy for SMA 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 at the end of February this year 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 Original source: FDA grants priority review to Roche's risdiplam for strategic strategic toxicology