Evrysdi (risdiplam) / SMA Foundation, PTC Therap, Roche, Royalty - LARVOL DELTA

Impaired renal function in patients with spinal muscular atrophy: a longitudinal cohort study (ERA 2025) - " We collected baseline data before the start of SMN-augmenting therapies (nusinersen and risdiplam) and during follow-up (maximum range 18-30 months). Assessing renal clearance with cystatin C shows that patients with SMA are at risk of impaired renal function, which does not improve after 1-2 years treatment with SMN2-splicing modifying therapies. Tubular function may improve partially following the start of treatment. These data indicate that SMN protein deficiency not only affects motor neurons but also affects peripheral tissues with high expression levels and that the incomplete functional rescue during treatment indicates health risks in later life."

Clinical • Amyotrophic Lateral Sclerosis • Chronic Kidney Disease • Genetic Disorders • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Nephrology • Rare Diseases • Renal Calculi • Renal Disease • CST3 • SMA4 • SMN1 • SMN2

Two-year Risdiplam treatment in adults with spinal muscular atrophy: improvements in motor and respiratory function, quality of life and fatigue. (PubMed, Neuromuscul Disord) - "Improvements in quality of life were observed, along with a reduction in fatigue and dysphagia. The safety profile was favorable."

HEOR • Journal • CNS Disorders • Fatigue • Gastrointestinal Disorder • Genetic Disorders • Movement Disorders • Muscular Atrophy • Otorhinolaryngology • Rare Diseases

Roche’s Evrysdi tablet approved by European Commission as first and only for Spinal Muscular Atrophy (SMA) (Roche Press Release) - "Roche...announced today that the European Commission (EC) has approved a label extension for Evrysdi (risdiplam) to include a new, room-temperature stable tablet for people living with spinal muscular atrophy (SMA). The 5mg tablet (approx. 6.5mm), which can either be swallowed whole or dispersed in water, can be taken with or without food and does not require refrigeration, when stored at room temperature. Administered at home, Evrysdi is the only non-invasive disease modifying treatment available for people living with SMA...The approval is based on data from a bioequivalence study (NCT04718181) evaluating the 5mg tablet formulation of Evrysdi, which can either be swallowed whole or dispersed in water."

EMA approval • Muscular Atrophy

Role of External Control Arm (ECA) Derived from Real World Data (RWD) in US FDA Regulatory Approval from 2020-2024 (ISPOR 2025) - "OBJECTIVES: To analyze role of ECA in US FDA approvals ( 2020 - 2024) & summarize the key disease areas leveraging ECA. systematic literature review and analysis of all novel drug approvals including NDA (New Drug Application) and BLA (Biological License Application)submitted from 2020-2024 were analyzed. The percentage of approvals involving external control arms increased steadily, particularly in rare diseases, oncology, and conditions with small or hard-to-recruit patient populations from 2020-2024 2020: Early Exploration (5-7% of Approvals) : 1.Ibrance (palbociclib): Used retrospective RWD to support male breast cancer indication...Blincyto (blinatumomab): Supplemental approvals for rare cancers based on external data. 2021: Accelerated Adoption Amid COVID-19 (10-15% of Approvals) 1.Veklury (remdesivir): Approval supported by real-world hospital data as external comparisons...Keytruda (pembrolizumab): Label expansion for certain cancers using external control..."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Summary of Evolving Role and Impact of Real World Evidence (RWE) in US FDA Regulatory Approvals (2020-2024) (ISPOR 2025) - "Notable cases like Rozlytrek (entrectinib) for rare cancers leveraged synthetic control arms, Zolgensma (onasemnogene abeparvovec-xioi) used RWE for expanded indications...Examples include Enhertu (fam-trastuzumab deruxtecan-nxki) for HER2-low breast cancer and Evrysdi (risdiplam) for spinal muscular atrophy, supported by longitudinal real-world data. 1) 2020, RWE was primarily used in label expansions and post-marketing safety evaluations, particularly in oncology and rare diseases. Notable approvals included Ibrance (palbociclib) for male breast cancer, based on real-world data from EHRs.2) 2021, during COVID-19 pandemic, RWE played a key role in Emergency Use Authorizations (EUAs) and full approvals of treatments like Veklury (remdesivir). The % of approvals involving RWE increased to 15-20%, with RWE supporting label expansions for drugs like Keytruda (pembrolizumab).3)2022, RWE contributed to 25-30% of approvals, including initial NDAs and BLAs."

Clinical • HEOR • Real-world • Real-world evidence • Alzheimer's Disease • Breast Cancer • CNS Disorders • Genetic Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Male Breast Cancer • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Oncology • Rare Diseases • Solid Tumor • HER-2

Combined Pulmonary and Neurology Clinic - One Center's Experience With Spinal Muscular Atrophy (ATS 2025) - "The study will compare those receiving disease-modifying treatments, such as nusinersen (antisense oligonucleotide) or risdiplam (SMN2 pre-mRNA splicing modifier), to patients who have received gene therapy in addition to these treatments. Gene therapy improved maximal motor milestones reached in patients with SMA at Connecticut Children's. Future plans involve continuous assessment of the impact of these interventions including pulmonary function testing, growth and development, exacerbations, and the development of co-morbid conditions. The small number of patients likely limited the ability to detect a noticeable difference between treatment groups."

Gene Therapies • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pulmonary Disease • Rare Diseases • SMN2

DIFFICULTIES OF EATING AND MASTICATING SOLID FOOD IN CHIDREN WITH SPINAL MUSCULAR ATROPHY – PRELIMINARY STUDY (ESPGHAN 2025) - "Methods We investigated 17 children with SMA (aged 7; 5 ± 2; 11), treated with various medications: nusinersen (n=13), risdiplam (n=4), branaplam (n=2), and onasemnogene (n=5)...Conclusions Difficulties with oral feeding still can affect patients with SMA, despite the treatment. Weakened tongue muscle strength can results in reduce effectiveness in eating solid foods."

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

Assessing Risdiplam Cost-Effectiveness for Spinal Muscular Atrophy Types I, II, and III in Chile (ISPOR 2025) - "OBJECTIVES: This study evaluates the cost-effectiveness of risdiplam compared to nusinersen and onasemnogene abeparvovec (AVXS-101) in patients with Spinal Muscular Atrophy (SMA) types I, II, & III over a 10-year horizon from a societal perspective in Chile, incorporating both direct healthcare costs and indirect costs related to productivity loss... In conclusion, risdiplam emerges as the preferred option for SMA patients, demonstrating superior effectiveness and cost advantages over alternative treatments. Sensitivity analyses confirm the robustness of the base case findings, reinforcing risdiplam's dominance. From a cost-effectiveness perspective, risdiplam offers the most convenient alternative for the Chilean public health system in all SMA types."

Cost effectiveness • HEOR • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Post-Marketing Safety of Spinal Muscular Atrophy Therapies: Analysis of Spontaneous Adverse Drug Reactions from EudraVigilance. (PubMed, J Clin Med) - "Background/Objectives: Spinal muscular atrophy (SMA) treatment has evolved with the approval of nusinersen, onasemnogene abeparvovec, and risdiplam...ADRs related to SMA complications require careful differentiation from true drug-related effects. Future pharmacovigilance efforts should focus on long-term safety assessments and real-world evidence to optimize treatment strategies."

Adverse drug reaction • Journal • P4 data • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pneumonia • Rare Diseases • Respiratory Diseases

The Impact of Family Spillover Effects in Economic Evaluation for SMA Type 1 Treatments in the United States (ISPOR 2025) - "A hypothetical comparator was created to reflect the weighted average clinical outcomes and wholesale acquisition costs of three available SMA type 1 treatments (Spinraza, Zolgensma, Evrysdi) using efficacy data from a published matching-adjusted indirect treatment comparison and real-world utilization patterns... The addition of FSE for primary informal caregivers of children with SMA Type 1 led to a projected 54% reduction in the base-case ICER. Future CEAs should explore FSE using available caregiver data and productivity algorithms to estimate treatment impacts and value for the family."

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

Navigating Treatment Barriers for SMA Type 1: Insights from Payer Policies and Parental Experiences [WITHDRAWN] (ISPOR 2025) - "OBJECTIVES: To examine US payer medication policies for initial and secondary treatments for children with spinal muscular atrophy type 1 (SMA 1) and to evaluate their impact on obtaining these treatments as described through parental narratives. We analyzed 48 US payer policies using the Tufts Medical Center Specialty Drug Evidence and Coverage database to evaluate coverage criteria for three FDA-approved SMA treatments: onasemnogene abeparvovec-xioi (OA), nusinersen, and risdiplam... This study revealed policy-driven barriers to SMA treatment. Delays in treatment initiation and approval appear to have exacerbated caregiver burden and negative health outcomes. The demand for sequential and combination treatment strategies further complicates this landscape, emphasizing the need for research on multi-pronged treatment strategies."

Genetic Disorders • Mood Disorders • Movement Disorders • Muscular Atrophy • Psychiatry • Rare Diseases

Tunable Gene Control via RNA Splicing with Clinically Approved Small Molecule (ASGCT 2025) - "We have developed a novel small molecule–inducible gene expression system leveraging the clinically approved, orally bioavailable splice modifier risdiplam...This system provides a versatile and clinically feasible tool for controlled transgene expression without the drawbacks of existing systems. Its application could improve the safety and efficacy of gene therapies and gene editing approaches by offering dose flexibility, reversibility, and a reduced risk of adverse effects."

Clinical • Late-breaking abstract • Gene Therapies • SMN2

Innovative Intrathecal AAV9-mediated Gene Therapy for Spinal Muscular Atrophy: Phase I/II Safety and Efficacy Topline Results (ASGCT 2025) - "GC101, an intrathecal AAV9-mediated gene therapy, is well-tolerated and shows promising efficacy in Type 2 SMA patients. Patients previously treated with Nusinersen and/or Risdiplam can safely benefit from GC101. These results support GC101's ongoing development as a potential Type 2 SMA treatment, with further studies needed to assess long-term safety and efficacy."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Pediatrics • Rare Diseases • Respiratory Diseases • SMA4 • SMN1

REACH: Adult SMA Research and Clinical Hub (clinicaltrials.gov) - P=N/A | N=600 | Recruiting | Sponsor: Newcastle-upon-Tyne Hospitals NHS Trust

New trial • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Short Review on Currently Used Sample Preparation and Determination Methods of Risdiplam. (PubMed, J Sep Sci) - "Challenges associated with the risdiplam analytics include developing a highly sensitive and selective method in biological matrices and dealing with potential interferences from the biological matrix. Future research should focus on improving analytical methods, investigating metabolite activity, and expanding our knowledge of its long-term effects."

Journal • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1

Safety of risdiplam in patients with spinal muscular atrophy: a postmarketing surveillance study (JSNE 2025) - No abstract available

Clinical • P4 data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

A Study to Learn About the Effect of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Risdiplam (ASCEND) (clinicaltrials.gov) - P3 | N=45 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN1

NMR analysis of interaction between RNA structure elements and small molecules. (PubMed, J Biochem) - "The interaction of designed RNAs and three kind of small molecules, risdiplam, naphthyridine carbamate dimer (NCD) and ciprofloxacin, were examined by NMR spectroscopy. Among the three compounds, NCD shows relatively stronger affinity to some of the model RNAs as judged by the NMR spectra, and binding sites of NCD for two RNAs were determined. The measurement condition used in this work, including the annealing free sample preparation as well as the Mg2+ free sodium phosphate buffer, can be the standard for initial the NMR screening in the RNA-targeted small molecule drug discovery."

Journal

Cost-effectiveness analysis of Risdiplam and Nusinersen for the treatment of Chinese patients with spinal muscular atrophy. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "Sensitivity analysis results showed the cost of RI and NU had a significant effect on ICER as well as proving the stability of results. RI is a cost-effective option compared to NU in SMA treatment."

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

Clinical Application of Risdiplam in 5q Spinal Muscular Atrophy: A Narrative Review. (PubMed, Br J Hosp Med (Lond)) - "This article reviews the drug trials of Risdiplam, summarizes the actual clinical data, and systematically evaluates the effectiveness and safety of this drug. By discussing the mechanism of action and economic cost of this drug and comparing it to other SMA drugs, this paper provides a reference for the clinical use of the drug and an idea for future clinical research."

Journal • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMN2

Nusinersen combined with risdiplam for the treatment of spinal muscular atrophy: a case series of 10 patients and literature review (PubMed, Zhongguo Dang Dai Er Ke Za Zhi) - "Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed."

Journal • Retrospective data • Review • Genetic Disorders • Movement Disorders • Muscular Atrophy • Pain • Pediatrics • Rare Diseases

Natco Pharma update on launch of Risdiplam in India (Business Standard) - "Natco Pharma today updates on the legal proceedings on Risdiplam launch in India.The Company has received numerous enquiries from investors and patients about the launch, availability and pricing of generic version of Risdiplam in the Indian market. The Company wishes to clarify that the Ld. Single Judge of Delhi High Court had through order dated 24 March 2025 denied Roche's plea for an injunction against the Company for the drug....Subject to the foregoing, the Company has decided to price the product at Rs 15,900 MRP consistent with the Company's stand before the court. The Company also intends to offer discount to certain deserving patients through its patient access programme."

Generic launch • Pricing • Muscular Atrophy

Balancing Innovation and Accessibility: The Role of Pharmaceutical Patents in Public Interest (Bar & Bench) - "The Delhi High Court delivered a decisive ruling in the patent infringement case brought by F Hoffmann-La Roche AG against NATCO Pharma Limited, concerning Roche's patent for 'Risdiplam,' marketed under the brand name 'EVRYSDI.' This drug is the only approved oral treatment in India for Spinal Muscular Atrophy (SMA), a rare genetic neuromuscular disorder.....Roche's patent, IN 334397 (also referred to as IN’397 or the Suit Patent), titled 'COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY,' specifically concerns the molecule Risdiplam. This patent grants exclusivity over Risdiplam until May 2035."

Patent • Muscular Atrophy

Upper limb motor function in individuals with SMA type 2: natural history and impact of therapies. (PubMed, J Neurol) - "Our findings provide a natural history of upper extremity motor function in children and adolescents with SMA type 2. The RULM scores typically improve during the early years of life, peaking around 4.4 years of age, after which they progressively decline with age. The data presented here will facilitate the assessment of treatment response in individuals with SMA type 2, especially in those with already severely limited motor function."

Journal • Observational data • Retrospective data • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Patients on treatment with risdiplam in Italy: challenges in the interpretation of the real-world data. (PubMed, Neurol Sci) - "This is the largest cohort described so far providing insights on the characteristics of patients on risdiplam in the real world. The disability level and age were very different from those that had driven efficacy results in the trials. This may at least in part produce some evidence to account for the variable results reported so far in the realworld. Importantly, the safety profile was confirmed even in these more severely disabled and older patients compared to those in the trials."

Journal • Real-world evidence • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases