DRUGapprovedsplice modifier
risdiplam
Brand names: Evrysdi
Mechanism
Small molecule SMN2 splicing modifier. Promotes exon 7 inclusion. Oral, crosses BBB.
Approved indications
type1type2type3
Structure
CC1=CC(=NN2C1=NC(=C2)C)C3=CC(=O)N4C=C(C=CC4=N3)N5CCNC6(C5)CC6
PubChem CID 118513932
Related claims (50)
| Type | Predicate | Conf | Source |
|---|---|---|---|
| motor function | The CHOPINTEND score increased by 2.7 points/month (95%CI 2.1 to 3.3, p < 0.001) in SMA patients with 2 copies of survival motor neuron 2 gene receiving risdiplam (clinical trial result). | 69% | 40745614 |
| biomarker | SMN protein is an appropriate biomarker for monitoring and evaluating the efficacy of risdiplam treatment in SMA. | 65% | 40795449 |
| splicing event | A low-dose treatment of Anti-N1 with either risdiplam or branaplam produces a synergistic effect on the inclusion of SMN2 exon 7 in SMA patient fibroblasts (demonstrated in vitro). | 65% | 38379891 |
| drug efficacy | Risdiplam treatment showed statistically significant improvements in the 32-item Motor Function Measure (MFM32) (clinical trial result) | 65% | 37891788 |
| drug efficacy | Risdiplam treatment shows clinical improvements in SMA type I patient with only one SMN2 copy. | 65% | 38520738 |
| drug efficacy | Risdiplam treatment was associated with improvement in the EK2 (p = .009) in adult SMA patients (clinical trial result). | 65% | 36382958 |
| splicing event | Evrysdi™ (risdiplam) promotes exon 7 inclusion to generate full-length SMN2 mRNA (mechanism unspecified). | 65% | 34368854 |
| motor function | The CHOPINTEND score increased by 2.7 points/month (95%CI 2.4 to 3.0, p < 0.001) in SMA children with type 1 receiving risdiplam (clinical trial result). | 64% | 40745614 |
| motor function | The CHOPINTEND score increased by 1.8 points/month (95%CI 0.8 to 2.9, p = 0.001) in SMA children with short disease duration before risdiplam treatment (clinical trial result). | 64% | 40745614 |
| drug efficacy | After 12 months of treatment with risdiplam, 57% of participants with SMA1 achieved a CHOP-INTEND score ≥ 40 points (clinical trial result). | 64% | 37574770 |
| motor function | Of the children whose motor function was assessed with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders and/or the Hammersmith Functional Motor Scale - Expanded after risdiplam initiation, nearly all (n = 12/13... | 60% | 40624473 |
| safety | Diverging patterns in adverse reaction reporting suggest a stabilizing safety profile for nusinersen and potential emerging safety signals for risdiplam and onasemnogene abeparvovec. | 59% | 41149786 |
| safety | Risdiplam was generally well tolerated, with predominantly mild and non-specific adverse events reported in 14.0% of patients (observed in patient cohort). | 59% | 41181835 |
| motor function | Risdiplam resulted in a significant improvement in motor function compared with placebo in patients aged 2-25 years with type 2 or non-ambulant type 3 spinal muscular atrophy (clinical trial result). | 59% | 34942136 |
| drug efficacy | Risdiplam treatment resulted in remarkable improvement in motor function (case report). | 59% | 39093767 |
| motor function | Nusinersen and risdiplam showed improvements in motor function and milestones (clinical trial result). | 59% | 41350238 |
| motor function | Risdiplam resulted in improvement or stabilization in motor functions (observed in patient cohort). | 59% | 39568039 |
| splicing event | Therapeutic approaches that have been undertaken include correction of the aberrant SMN2 splicing using an antisense oligonucleotide (ASO) or small molecule (nusinersin, risdiplam). | 59% | 32056234 |
| splicing event | Risdiplam acts as a <i>survival motor neuron 2</i> (<i>SMN2</i>) pre-mRNA splicing modifier. | 59% | 35316106 |
| splicing event | Risdiplam modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. | 59% | W3174394828 |
| drug efficacy | Risdiplam reduced steatosis by 65.9% in SMA patient-derived iHeps (demonstrated in vitro) | 59% | 41567114 |
| motor function | After risdiplam initiation, six (30%) children had improvements in respiratory function (observed in patient cohort) | 59% | 40624473 |
| drug efficacy | Risdiplam is an efficacious treatment for persons with symptomatic spinal muscular atrophy (SMA). | 59% | 40802943 |
| splicing event | Risdiplam is an RNA splicing modifier that modifies pre-mRNA splicing of the SMN2 gene, thereby promoting the production of functional survival motor neuron protein (SMN-fl). | 59% | 40265545 |
| drug efficacy | Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA (clinical trial result). | 59% | 40241365 |
| motor function | Risdiplam demonstrated a noticeable improvement in Hammersmith functional motor scale expanded (HFMSE) score in 13 SMA patients at the last follow-up compared with baseline (clinical trial result). | 59% | 40745614 |
| motor function | In this first matched-pair comparison of nusinersen and risdiplam in adults with SMA, both treatments achieved similar stabilization of motor function over almost three years (clinical trial result). | 59% | 41484582 |
| motor function | Children treated with risdiplam also had a 45% higher rate of achieving a Hammersmith Infant Neurological Examination, Module 2 motor milestone response compared with children treated with nusinersen (clinical trial result). | 59% | 38705943 |
| gene expression | Risdiplam increases levels of functional SMN protein (clinical trial result). | 59% | 33626251 |
| survival | Risdiplam showed a survival rate of 86% [95% CI: 76, 94] (clinical trial result). | 59% | 39604484 |
| motor function | Motor function improvements were consistent with nusinersen and risdiplam (clinical trial result). | 59% | 41350238 |
| drug efficacy | The treatment of SMA with nusinersen, onasemnogene abeparvovec, and risdiplam changes the disease phenotype with changes in motor function far exceeding any improvement in respiratory and nutritional function (clinical trial result). | 59% | 38905882 |
| drug efficacy | Two patients were the first presymptomatic patients with two copies of <i>SMN2</i> to receive treatment with Risdiplam in Spain. | 59% | 39846593 |
| safety | Children with type 1 SMA treated with risdiplam had a 57% reduction in the rate of serious adverse events compared with children treated with nusinersen (clinical trial result). | 59% | 38705943 |
| drug efficacy | Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e. nusinersen and risdiplam, improve motor function in SMA. | 59% | 37095427 |
| drug target | The PBPK analysis suggests that primary CYP3A inhibition by risdiplam occurs in the intestine rather than the liver. | 59% | 34347881 |
| drug efficacy | In SMA2/3, RULM increased by 1.73 points after treatment with risdiplam (clinical trial result). | 59% | 37574770 |
| splicing event | Risdiplam modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. | 59% | 34942136 |
| drug efficacy | Nusinersen and risdiplam treatment showed clinically meaningful improvement in motor function (clinical trial result) | 59% | 37891788 |
| motor function | Indirect comparison results found improved motor function with risdiplam versus nusinersen (clinical trial result) | 59% | 35040693 |
| splicing event | Both Risdiplam and Branaplam triggered massive perturbations of splicing events, inducing off-target exon inclusion, exon skipping, intron retention, intron removal and alternative splice site usage (observed in SMA patient cells). | 59% | 37026480 |
| splicing event | Risdiplam modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene. | 59% | 36244364 |
| motor function | Risdiplam improves motor neuron function in patients with spinal muscular atrophy (SMA). | 59% | 34347881 |
| splicing event | Risdiplam is an oral splicing modifier for the survival motor neuron-2 gene (SMN2). | 59% | 40782291 |
| drug efficacy | Treatment with nusinersen or risdiplam resulted in reduction of the number of patients with hypokalaemia (observed in patient cohort). | 59% | 41540943 |
| splicing event | Risdiplam is an orally administered, small-molecule SMN2 pre-mRNA splicing modifier. | 59% | 30519476 |
| motor function | Risdiplam over 24 months resulted in further improvement or stabilization in motor function (clinical trial result). | 59% | 36735057 |
| gene expression | Risdiplam increases levels of functional SMN protein in blood (clinical trial result). | 59% | 34320287 |
| motor function | Treatment with risdiplam over 24 months resulted in continual improvements in motor function (clinical trial result). | 59% | 36244364 |
| drug efficacy | Expedited therapy initiation, including reversible treatments like nusinersen or risdiplam, is recommended without waiting for the completion of the molecular testing, thus minimizing delays in crucial therapeutic interventions. | 59% | 40900970 |
Off-Target Findings (244)
T1: 2T3: 221untiered: 21
| Target | Role | Tier | Boltz-2 iPTM | Chai-1 iPTM | Verdict |
|---|---|---|---|---|---|
| KCNA2ion_channel | SMA | T1 | 0.455 | — | Primary SMA hit |
| SCN5Aion_channel | SMA | T1 | 0.406 | — | Primary SMA hit |
| S1PR5gpcr | OFF-TARGET | T3 | 0.983 | — | Selectivity flag (off-target substrate) |
| GPR42gpcr | OFF-TARGET | T3 | 0.982 | — | Selectivity flag (off-target substrate) |
| FFAR3gpcr | OFF-TARGET | T3 | 0.979 | — | Selectivity flag (off-target substrate) |
| LTB4R2gpcr | OFF-TARGET | T3 | 0.970 | — | Selectivity flag (off-target substrate) |
| ADORA1gpcr | OFF-TARGET | T3 | 0.962 | — | Selectivity flag (off-target substrate) |
| GPR18gpcr | OFF-TARGET | T3 | 0.959 | — | Selectivity flag (off-target substrate) |
| CCKBRgpcr | OFF-TARGET | T3 | 0.958 | — | Selectivity flag (off-target substrate) |
| TACR2gpcr | OFF-TARGET | T3 | 0.957 | — | Selectivity flag (off-target substrate) |
| FPR2gpcr | OFF-TARGET | T3 | 0.957 | — | Selectivity flag (off-target substrate) |
| HRH2gpcr | OFF-TARGET | T3 | 0.953 | — | Selectivity flag (off-target substrate) |
| ACKR3gpcr | OFF-TARGET | T3 | 0.951 | — | Selectivity flag (off-target substrate) |
| P2RY6gpcr | OFF-TARGET | T3 | 0.949 | — | Selectivity flag (off-target substrate) |
| TAAR5gpcr | OFF-TARGET | T3 | 0.948 | — | Selectivity flag (off-target substrate) |
| TACR3gpcr | OFF-TARGET | T3 | 0.947 | — | Selectivity flag (off-target substrate) |
| MCHR1gpcr | OFF-TARGET | T3 | 0.947 | — | Selectivity flag (off-target substrate) |
| TBXA2Rgpcr | OFF-TARGET | T3 | 0.944 | — | Selectivity flag (off-target substrate) |
| AURKCkinase | OFF-TARGET | T3 | 0.943 | — | Selectivity flag (off-target substrate) |
| P2RY2gpcr | OFF-TARGET | T3 | 0.940 | — | Selectivity flag (off-target substrate) |
| MRGPRX4gpcr | OFF-TARGET | T3 | 0.939 | — | Selectivity flag (off-target substrate) |
| CX3CR1gpcr | OFF-TARGET | T3 | 0.938 | — | Selectivity flag (off-target substrate) |
| GPR3gpcr | OFF-TARGET | T3 | 0.936 | — | Selectivity flag (off-target substrate) |
| SCTRgpcr | OFF-TARGET | T3 | 0.928 | — | Selectivity flag (off-target substrate) |
| MTNR1Agpcr | OFF-TARGET | T3 | 0.927 | — | Selectivity flag (off-target substrate) |
| MTNR1Bgpcr | OFF-TARGET | T3 | 0.921 | — | Selectivity flag (off-target substrate) |
| MAP2K3kinase | OFF-TARGET | T3 | 0.918 | — | Selectivity flag (off-target substrate) |
| GPR31gpcr | OFF-TARGET | T3 | 0.917 | — | Selectivity flag (off-target substrate) |
| ADGRG3gpcr | OFF-TARGET | T3 | 0.917 | — | Selectivity flag (off-target substrate) |
| GPR4gpcr | OFF-TARGET | T3 | 0.912 | — | Selectivity flag (off-target substrate) |
| OXGR1gpcr | OFF-TARGET | T3 | 0.912 | — | Selectivity flag (off-target substrate) |
| ACKR4gpcr | OFF-TARGET | T3 | 0.910 | — | Selectivity flag (off-target substrate) |
| MERTKkinase | OFF-TARGET | T3 | 0.910 | — | Selectivity flag (off-target substrate) |
| ADGRE3gpcr | OFF-TARGET | T3 | 0.907 | — | Selectivity flag (off-target substrate) |
| PAK2kinase | OFF-TARGET | T3 | 0.907 | — | Selectivity flag (off-target substrate) |
| P2RY12gpcr | OFF-TARGET | T3 | 0.905 | — | Selectivity flag (off-target substrate) |
| LPAR6gpcr | OFF-TARGET | T3 | 0.905 | — | Selectivity flag (off-target substrate) |
| RHOgpcr | OFF-TARGET | T3 | 0.904 | — | Selectivity flag (off-target substrate) |
| GPR25gpcr | OFF-TARGET | T3 | 0.899 | — | Selectivity flag (off-target substrate) |
| AK4kinase | OFF-TARGET | T3 | 0.897 | — | Selectivity flag (off-target substrate) |
| GPR135gpcr | OFF-TARGET | T3 | 0.891 | — | Selectivity flag (off-target substrate) |
| HCRTR2gpcr | OFF-TARGET | T3 | 0.890 | — | Selectivity flag (off-target substrate) |
| GRK2kinase | OFF-TARGET | T3 | 0.890 | — | Selectivity flag (off-target substrate) |
| CDK20kinase | OFF-TARGET | T3 | 0.887 | — | Selectivity flag (off-target substrate) |
| HRH3gpcr | OFF-TARGET | T3 | 0.883 | — | Selectivity flag (off-target substrate) |
| CLK3kinase | OFF-TARGET | T3 | 0.882 | — | Selectivity flag (off-target substrate) |
| PTK6kinase | OFF-TARGET | T3 | 0.880 | — | Selectivity flag (off-target substrate) |
| HCRTR1gpcr | OFF-TARGET | T3 | 0.878 | — | Selectivity flag (off-target substrate) |
| AMHR2kinase | OFF-TARGET | T3 | 0.877 | — | Selectivity flag (off-target substrate) |
| CHEK1kinase | OFF-TARGET | T3 | 0.877 | — | Selectivity flag (off-target substrate) |
Showing top 50 of 244 targets.