Spinal muscular dystrophy (SMA) is the first oral medicine! Rocherisdiplam: Significantly improve motor function, quickly and continuously improve SMN protein levels!

, June 15, 2020 /
BIOON/
BioValley -- Roche recently released
two-year data on the treatment of patients with type 2 or 3 SMA in the first part of the oral drug Risdiplam SUNFISH Trial (Part 1) for the evaluation of spinal muscular dystrophy (SMA) at the Virtual Cure SMA Research and Clinical CareConferenceThe results of the exploratory efficacy analysis showed that the exercise function was significantly improved after 24 months of risdiplam treatment compared to data from the natural history of disease, Roche also released preliminary 12-month data from the JEWELFISH trialThe trial was conducted in all types of SMA patients who had previously received other SMA therapy, ages 6 months to 60 years, and 12 months of data showed that SMA protein levels increased rapidly and continuously after treatment with risdiplamNo new safety signals were observed, and the overall adverse events were consistent with patients with treatment-naiverisdiplam is an oral administered motor neuron survival gene 2 (SMN2) splicing modifier developed for all types (type 1, type 2, type 3) SMA treatmentCurrently, risdiplam's new drug application (NDA) is being reviewed by the U.SFDAIn early April, theFDAextended the NDA target action for three months until August 24The review cycle was extended because Roche submitted additional data that ensured access to risdiplam treatment for a wide range of SMA patientsif approved,risdiplam would be the first oral drug to treat all three types of SMA as part of its partnership with the SMA Foundation and PTC Therapeutics, Roche led the clinical development of risdiplam If approved, Roche will be responsible for the commercialization of risdiplam in the United States "These 24-month exploratory data are important because they are consistent with the medically significant results we observed one year after the sunFISH Part II (Part 2) treatment, which represents a wide range of real-world SMA populations," said Dr Levi Garraway, chief medical officer and global product development officer at Roche We are also encouraged by the increase in SMN protein levels observed in the first part of the SUNFISH study and in the JEWELFISH study These data reinforce the potential of risdiplam and will make a real difference in the lives of many SMA patients "
SUNFISH study
SUNFISH is a large-scale (n-231), global two-part study of children and adults Dose discovery SUNFISH Part 1 (n-51) includes a wide range of patient groups ranging from being unable to sit and able to walk as well as scoliosis or joint contractions exploratory efficacy analysis in Part 1 of the SUNFISH study uses the Motion Function Measurement (MFM) scale to evaluate motion function MFM is an effective scale for evaluating fine and large motor functionin in patients with neurological disorders, including SMA It evaluates different motor functions, from standing and walking to using hands and fingers In the weighted analysis, when the data were compared with a robust natural history control group, patients treated with risdiplam had a greater change in the total MFM score from the baseline during the 24th month (difference: 3.99 points; 95% CI: 2.34-5.65; p 0.0001) Even small changes in motor function led to meaningful differences in daily life results showed that the blood SMN level increased by at least 4 months after treatment with risdiplam, and the average level of blood SMN levels increased by 22 months This is in line with the previously reported 12-month treatment The SMN protein is present throughout the body and is essential for maintaining healthy motor neurons that transmit motor signals from the central nervous system to the muscles these results were consistent with the 12-month results of non-bedridden patients in Part 2 of the SUNFISH study, which showed that the total MFM32 scores of patients treated with risdiplam varied significantly from baseline levels (average difference: 1.55 points; p-0.0156) compared to the placebo group in SunFISH Part 1, the most common adverse were fever (fever; 55 percent), cough (35 percent), vomiting (33 percent), upper respiratory tract infection (31 percent), cold (nanopharyplicitis; 24 percent) and sore throat (sore throat; 22 percent) The most common serious adverse event in 51 patients treated with risdiplam was pneumonia, which occurred in 3 patients To date, there have been no treatment-related safety findings that lead to discontinuation JEWELFISH Research THE JEWELFISH STUDY HAS COMPLETED THE PATIENT IN-GROUP (N-174) The trial was conducted in all types of SMA patients who had previously been treated with other SMA therapies, who are now undergoing risdiplam treatment, and the study is evaluating safety data and pharmacological data In patients who completed 12 months of risdiplam treatment (n-18), SMN protein levels were observed to increase by 2 times the median than the baseline level Early safety assessments showed consistent safety with patients with treatment-naive of the 174 patients enrolled in the group, 76 had received the antithesis drug Spinrazersen and 14 had been treated with The gene therapy Zolgensma (onasemnogene abeparvovec), Novartis The remaining 83 patients were treated with compounds developed by Roche the most common adverse reaction
s were upper respiratory tract infections (13 per cent), headache (12 per cent), fever (8 per cent), diarrhoea (8 per cent), nasopharyngitis (7 per cent) and nausea (7 per cent) To date, no drug-related safety findings have led to patients withdrawing from the JEWELFISH trial, and the overall adverse events are similar to those observed in patients who were not previously treated with SMA targeting in the risdiplam trial risdiplam chemical structure (photo: medchemexpress.cn) risdiplam is an oral liquid, motor neuron survival gene 2 (SMN2) splicing modifier designed to continuously increase and maintain SMN protein levels in the central nervous system and peripheral tissues A growing number of clinical evidence shows that SMA is a multi-system disease, and the loss of SMA proteinmay affect many tissues and cells outside the central nervous system Risdiplam's oral administration showed systemic distribution, which consistently increased SMN protein levels in the central nervous system and peripheral tissues, and has been shown to improve motor function in patients with type 1, type 2 and Type 3 SMA is expected to become the first oral drug to treat all three types of SMA Risdiplam is an oral liquid preparation that, if approved, would be the first at home for SMA patients Previously, the FDA had granted risdiplam orphan drugs and fast-track status risdiplam is conducting research in a wide range of SMA clinical trials, with a group of patients ranging from newborns to 60 years of age, including pre-symptom patients and patients who have previously received other SMA therapies The Clinical Trials program is designed to represent a wide range of people with the disease in the real world to ensure that all suitable patients have access to risdiplam treatment as part of its ongoing commitment to SMA patients, Roche has also submitted applications in Brazil, Chile, Indonesia, Russia, South Korea and Taiwan In the Chinese mainland filing, the company is currently planning to submit a listing application to the European Medicines Agency (EMA) and other international markets by mid-2020 Spinraza: The world's first SMA treatment has been approved in China
SMA is a motor neurone disease that causes muscle weakness and atrophy, which is an autosomal recessive genetic disease caused by genetic defects, which causes damage to the muscles in the patient's body, mainly as the whole body muscle atrophy, the body gradually loses various motor functions, even breathing and swallowing SMA is the number one genetic disease in infants under 2 years of age, a relatively common "rare disease" with a prevalence rate of 1:6000-1:10000 in newborns According to relevant reports, the number of SMA patients in China is about 3-5 million December 2016, spinraza ,nusinersen, a drug developed by YanJian and partner Ionis, was approved as the world's first drug to treat SMA The drug is an antisense oligonucleotide (ASO) that delivers the drug directly to the cerebrospinal fluid (CSF) around the spinal cord through intrauterine injection, alters the splicing of the SMN2 pre-messenger RNA (pre-mRNA) and increases the production of fully functional SMN proteins In Patients with SMA, insufficient levels of SMN protein led to degeneration of motor neuronfunction in the spinal cord In clinical studies, Spinraza therapy significantly improved motor function in SMA patients May 2019, Zolgensma, a gene therapy from Novartis, was approved to become the world's first gene therapy for SMA The drug through a single, one-time intravenous infusion after continuous expression of SMN protein to stop the disease process, can solve the fundamental cause of SMA, is expected to improve the quality of life of patients in the long term in the Chinese market, Spinraza was approved at the end of February 2019 for the treatment of patients with 5q myotrophic muscular dystrophy (5q-SMA) The approval makes Spinraza the first drug to treat SMA in the Chinese market 5q-SMA is the most common type of SMA, accounting for about 95% of all SMA cases, and this type of SMA is caused by a mutation in the SMN1 (motor neuron survival protein 1) gene on chromosome 5, hence the name 5q-SMA (BioValleyBioon.com) original source: Genentech Announcs 2-Year Risdiplam Data From FROM SUNFISH and New Data JEWEL FromFISH in Infants, Children and Adults With Spinal Atrophy (SMA)