Roche oral therapy reached the end point of three phases

Today, Roche's Genentech company announced that its oral SMN2 gene splicing regulator risdiplam significantly improved the motor function of patients in the critical phase 3 trial of sunfish in the treatment of type 2 or 3 spinal muscular atrophy (SMA) The trial is the first to show that risdiplam treatment improves motor function in adult SMA patients, the press release said The pathogenesis of SMA is due to the absence or abnormality of a protein called survival motor neuron (SMN) SMN protein is very important to maintain the survival of human motor neurons There are two genes that can generate SMN protein in human body, SMN1 gene and SMN2 gene, but SMN1 gene plays a leading role SMN2 gene only produces a small amount of SMN protein (about 10%) Therefore, once the function of SMN1 gene is abnormal, the patient will not be able to generate enough survival protein of motor neurons, the motor neurons of the patient will die rapidly, the muscle function will gradually lose, and eventually lead to paralysis, and can not complete the basic life-sustaining activities such as swallowing and breathing, which seriously threatens the life of the patient Although SMA mainly occurs in infants and young children, patients may be at any age from infants to adults Clinically, SMA is usually divided into type 1, type 2 and type 3, i.e infant, intermediate and adult Risdiplam (rg7916) is an oral SMN2 gene splicing regulator jointly developed by Genentech, PTC therapeutics and SMA foundation It can improve the expression of SMN protein in the central nervous system (CNS) and peripheral by regulating the splicing process of SMN2 mRNA This strategy for SMA treatment is very similar to spinraza, which has been approved The difference is that spinraza uses antisense oligonucleotides (ASOs) to regulate RNA splicing, which requires direct injection into CSF Risdiplam is a small molecule drug that can be taken orally Clinical trials have shown that risdiplam has excellent efficacy in the treatment of type 1 SMA infants At present, it is treating SMA patients aged 0 to 60 in a number of clinical trials ▲ risdiplam improves SMN protein level by regulating SMN2 RNA splicing (photo source: PTC therapeutics official website) In a three-stage clinical trial, a double-blind, placebo-controlled group, called sunfish, type 2 and type 3 SMA patients between the ages of 2 and 25 years were treated with risdiplam The test data showed that after 1 year of treatment, compared with the placebo group, patients in the treatment group achieved a statistically significant improvement in their motor function assessment scale (mfm-32) score compared with the baseline, which was the main end point of the study In addition, patients who received risdiplam treatment also showed improvement at this secondary end point through the evaluation of the upper extremity movement assessment scale (rulm) In addition, it is worth mentioning that the treatment group had more stable disease (57.1% vs 37.5%) in the 18-25-year-old subgroup For patients who have been ill for a long time, stability is the main goal reference material: [1] Genentech’s Risdiplam Showed Significant Improvement in Motor Function in People Aged 2-25 With Type 2 or 3 Spinal Muscular Atrophy，Retrieved February 06, 2020, from https:// Note: the original text has been deleted A kind of