RG7800 / SMA Foundation, Roche, PTC Therap - LARVOL DELTA

JEWELFISH: 24-month results from an open-label study in non-treatment-naïve patients with SMA receiving treatment with risdiplam. (PubMed, J Neurol) - P1, P2 | "JEWELFISH enrolled adult and pediatric patients (N = 174) with confirmed diagnosis of 5q-autosomal recessive SMA who had previously received treatment with nusinersen (n = 76), onasemnogene abeparvovec (n = 14), olesoxime (n = 71), or were enrolled in the MOONFISH study (NCT02240355) of the splicing modifier RG7800 (n = 13)...Exploratory efficacy outcomes are reported but it should be noted that the main aim of JEWELFISH was to assess safety and PK/PD, and the study was not designed for efficacy analysis. TRIAL REGISTRATION: The study was registered (NCT03032172) on ClinicalTrials.gov on January 24, 2017; First patient enrolled: March 3, 2017."

Journal • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pediatrics • Pneumonia • Rare Diseases • Respiratory Diseases

JEWELFISH: 24-month safety, pharmacodynamic and exploratory efficacy data in non-treatment-naïve patients with SMA receiving treatment with risdiplam (EPNS 2023) - P2, P2/3 | " JEWELFISH (NCT03032172) is a multicentre, open-label study of daily risdiplam in non-treatment-naïve patients with SMA (inclusion criteria aged 6 months-60 years at enrolment) who were previously enrolled in the MOONFISH study (RG7800) or previously treated with nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®)... JEWELFISH is ongoing at sites across Europe and the USA and is providing important data on the safety, PD and exploratory efficacy of risdiplam in a broad population of non-treatment-naïve patients with SMA."

Clinical • PK/PD data

JEWELFISH: 24-month Safety, Pharmacodynamic and Exploratory Efficacy Data in Non-Treatment-Naïve Patients with Spinal Muscular Atrophy (SMA) Receiving Treatment with Risdiplam (AAN 2023) - P2, P2/3 | "Design/Methods JEWELFISH (NCT03032172) is a multicenter, open-label study of daily risdiplam in non-treatment-naïve patients with SMA (inclusion criteria aged 6 months–60 years at enrollment) who were previously enrolled in the MOONFISH study (RG7800) or previously treated with nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®)...Based on the exploratory efficacy analysis, an overall stabilization of motor function was observed following 24 months of risdiplam treatment in patients 2–60 years as assessed by the 32-item Motor Function Measure and Revised Upper Limb Module scales (data-cut: 31 January 2022). Conclusions JEWELFISH is ongoing at sites across Europe and the USA and is providing important data on the safety, PD and exploratory efficacy of risdiplam in a broad population of non-treatment-naïve patients with SMA."

Clinical • PK/PD data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Reproductive findings in male animals exposed to selective survival of motor neuron-2 (SMN2) gene splicing modifying agents. (PubMed, Reprod Toxicol) - "In rats, seminiferous tubule degeneration was present, and full reversibility of germ cell degeneration in the testes was observed among half of the rats that were exposed to risdiplam or RG7800 and then allowed to recover. With these results, coupled with histopathological findings, the effects on the male reproductive system are expected to be reversible in humans for these types of SMN2 mRNA splicing modifiers."

Journal • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • FOXM1

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study. (PubMed, Neurol Ther) - P1, P2 | "The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients."

Journal • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pediatrics • Pneumonia • Rare Diseases • Respiratory Diseases

Safety update: Risdiplam clinical trial development program (WMS 2022) - P2, P2/3 | "JEWELFISH (NCT03032172) assesses safety, tolerability, PK and PD of risdiplam in patients with SMA (aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®)...Here we will present updated safety analyses from the risdiplam studies, including safety data from the RAINBOWFISH study. Safety data from across the risdiplam studies will add to the understanding of the long-term safety profile of risdiplam."

Clinical

JEWELFISH: 24-month safety and pharmacodynamic data in non-treatment-naïve patients with spinal muscular atrophy (SMA) (WMS 2022) - P2, P2/3 | "JEWELFISH (NCT03032172) is a multicenter, open-label study that assesses the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of daily risdiplam in non-treatment-naïve patients with SMA (aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®)...Here we will present the month 24 results from JEWELFISH for the first time. The JEWELFISH study is ongoing at sites across Europe and the USA and is providing important data on the safety and PD of risdiplam in a broad population of non-treatment-naïve patients with SMA."

Clinical • PK/PD data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Pooled Safety Data from the Risdiplam Clinical Trial Development Program (AAN 2022) - P2, P2/3 | "Design/ Safety data were pooled from three studies within the risdiplam clinical trial program: • FIREFISH (NCT02913482) assesses safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of risdiplam in infants with Type 1 SMA (aged 1–7 months at enrollment) • SUNFISH (NCT02908685) assesses safety, tolerability, PK, PD and efficacy of risdiplam in patients with Types 2/3 SMA (aged 2–25 years at enrollment)• JEWELFISH (NCT03032172) assesses safety, tolerability, PK and PD of risdiplam in patients with SMA (aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®)... Pooled data across the risdiplam studies suggest risdiplam has a positive benefit-risk profile. This analysis will add to the understanding of the long-term safety profile of risdiplam."

Clinical • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

JEWELFISH: Safety, Pharmacodynamic and Exploratory Efficacy Data in Non-Naïve Patients with Spinal Muscular Atrophy (SMA) Receiving Treatment with Risdiplam (AAN 2022) - P2 | "Design/ JEWELFISH (NCT03032172) is a multicenter, open-label study of daily risdiplam in non-naïve patients with SMA (inclusion criteria aged 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®)... JEWELFISH is ongoing at sites across Europe and the US, and will provide important data on the safety, PD and exploratory efficacy of risdiplam in a broad population of non-naïve patients with SMA."

Clinical • PK/PD data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic ∆7SMA mice. (PubMed, Neurobiol Dis) - "We found, compared with individual therapies, that morpholino antisense oligonucleotide (ASO) directed against ISS-N1 combined with the small molecule compound RG7800 significantly increased FL-SMN transcript and protein production resulting in improved survival and weight of ∆7SMA mice. Moreover, when give late symptomatically, motor unit function was completely rescued with no loss in function at 100 days of age in the dual treatment group. We have therefore shown that this dual therapeutic approach successfully increases SMN protein and rescues motor function in symptomatic ∆7SMA mice."

Journal • Preclinical • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4

[VIRTUAL] Pooled safety data from the risdiplam clinical trial development program (EAN 2021) - P2, P2/3 | " The risdiplam programme consists of four studies across a broad SMA population: • FIREFISH (NCT02913482): a 2-part study assessing safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA (inclusion criteria: 1–7 months at enrolment) • SUNFISH (NCT02908685): a 2-part study assessing safety, tolerability, PK, PD and efficacy in patients with Type 2 or 3 SMA (inclusion criteria: 2–25 years at enrolment) • JEWELFISH (NCT03032172), assessing safety, tolerability, PK and PD in patients with SMA (inclusion criteria: six months–60 years at enrolment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec- xioi (ZOLGENSMA®) • RAINBOWFISH (NCT03779334), assessing efficacy, safety, PK and PD in infants (inclusion criteria: birth–6 weeks at first dose) with genetically diagnosed and presymptomatic SMA... This analysis will add to the understanding of the..."

Clinical • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4

[VIRTUAL] JEWELFISH: 12-month safety, pharmacodynamic and exploratory efficacy of risdiplam in non-naïve patients with SMA (EAN 2021) - P2, P2/3 | "JEWELFISH participants have previously received nusinersen (SPINRAZA ®), onasemnogene abeparvovec-xioi (ZOLGENSMA®), olesoxime or RG7800 (RO6885247)... JEWELFISH is ongoing across Europe and the US and will provide important data on the safety, PD and exploratory efficacy of risdiplam in a heterogenous population of non-naïve patients with SMA."

Clinical • PK/PD data • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4

[VIRTUAL] Pooled Safety Data from the Risdiplam Clinical Trial Development Program (AAN 2021) - P2, P2/3 | "Design/ The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA: FIREFISH (NCT02913482) is a two-part study assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA (inclusion criteria 1–7 months at enrollment) SUNFISH (NCT02908685) is a two-part study assessing the safety, tolerability, PK, PD and efficacy in patients with Type 2 or 3 SMA (inclusion criteria 2–25 years at enrollment) JEWELFISH (NCT0302172) assesses the safety, tolerability, PK and PD in patients with SMA (inclusion criteria 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®). This analysis will add to the understanding of the long-term safety profile of risdiplam."

Clinical • CNS Disorders • SMA4

[VIRTUAL] JEWELFISH: Safety and Pharmacodynamic Data in Non-Naïve Patients with Spinal Muscular Atrophy (SMA) Receiving Treatment with Risdiplam (AAN 2021) - P2, P2/3 | "JEWELFISH participants previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®). The JEWELFISH study is ongoing in sites across Europe and the US and will provide important data on the safety and PD of risdiplam in non-naïve patients with SMA."

Clinical • PK/PD data • CNS Disorders • Muscular Atrophy • SMA4

[VIRTUAL] Pooled safety data from the risdiplam clinical trial development program (MDA 2021) - P2, P2/3 | "The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA:FIREFISH (NCT02913482) is a two-part study assessing the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA (inclusion criteria 1–7 months at enrollment)SUNFISH (NCT02908685) is a two-part study assessing the safety, tolerability, PK, PD and efficacy in patients with Type 2 or 3 SMA (inclusion criteria 2–25 years at enrollment)JEWELFISH (NCT0302172) assesses the safety, tolerability, PK and PD in patients with SMA (inclusion criteria 6 months–60 years at enrollment) who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®).RAINBOWFISH (NCT03779334) assesses the efficacy, safety, PK and PD in infants (inclusion criteria birth-6 weeks at first dose) with genetically diagnosed and presymptomatic SMA. This analysis will..."

Clinical • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4

[VIRTUAL] JEWELFISH: Safety and pharmacodynamic data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam (MDA 2021) - P2, P2/3 | "JEWELFISH participants previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®). JEWELFISH is ongoing in sites across Europe and the US and will provide important data on the safety and PD of risdiplam in non-naïve patients with SMA."

Clinical • PK/PD data • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4

Drug treatment for spinal muscular atrophy types II and III. (PubMed, Cochrane Database Syst Rev) - "Nusinersen improves motor function in SMA type II, based on moderate-certainty evidence. Creatine, gabapentin, hydroxyurea, phenylbutyrate, valproic acid and the combination of valproic acid and ALC probably have no clinically important effect on motor function in SMA types II or III (or both) based on low-certainty evidence, and olesoxime and somatropin may also have little to no clinically important effect but evidence was of very low-certainty. One trial of TRH did not measure motor function."

Journal • Review • Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Pooled Safety Data from the Risdiplam (RG7916) Clinical Trial Development Program (AAN 2020) - P2, P2/3 | "Design/ The risdiplam clinical development program consists of four studies in a broad population of individuals with SMA: FIREFISH (NCT02913482) aims to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of risdiplam in infants with Type 1 SMA aged 1–7 monthsSUNFISH (NCT02908685) aims to evaluate the safety, tolerability, PK/PD and efficacy of risdiplam in patients with Type 2 or 3 SMA aged 2–25 yearsJEWELFISH (NCT03032172) aims to assess the safety, tolerability and PK/PD of risdiplam in patients with SMA aged 6 months–60 years previously enrolled in Study BP29420 (MOONFISH) with the splicing modifier RG7800 (RO6885247) or who received previous treatment with nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®)RAINBOWFISH (NCT03779334) aims to investigate the efficacy, safety and PK/PD of risdiplam in newborns aged from birth to 6 weeks with genetically diagnosed and presymptomatic..."

Clinical • SMA4

JEWELFISH: Safety and Pharmacodynamic Data in Non-Naïve Patients with Spinal Muscular Atrophy (SMA) Receiving Treatment with Risdiplam (RG7916) (AAN 2020) - P2, P2/3 | "JEWELFISH participants previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec-xioi (ZOLGENSMA®). The JEWELFISH study is currently recruiting in sites across Europe and the US."

Clinical • PK/PD data • SMA4

The oral splicing modifier RG7800 increases full length survival of motor neuron 2 mRNA and survival of motor neuron protein: Results from trials in healthy adults and patients with spinal muscular atrophy. (PubMed, Neuromuscul Disord) - "RG7800 is an oral, selective SMN2 splicing modifier designed to modulate alternative splicing of SMN2 to increase the levels of functional SMN protein. In two trials, oral administration of RG7800 increased in blood full-length SMN2 mRNA expression in healthy adults and SMN protein levels in SMA patients by up to two-fold, which is expected to provide clinical benefit."

Clinical • Journal

Intraperitoneal Cefepime Monotherapy Versus Combination Therapy of Cefazolin Plus Ceftazidime for Empirical Treatment of CAPD-Associated Peritonitis: A Multicenter, Open-Label, Noninferiority, Randomized, Controlled Trial. (PubMed, Am J Kidney Dis) - P4 | "IP cefepime monotherapy was noninferior to conventional combination therapy for resolution of CAPD-associated peritonitis at day 10 and may be a reasonable alternative first-line treatment."

Clinical • Combination therapy • Head-to-Head • Journal • Monotherapy • Chronic Kidney Disease • Immunology • Nephrology • Renal Disease