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

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

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

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. Using an adapted Markov model, transitions between health states were assessed, accounting for disease progression and associated costs... 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

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 (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

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

Fertility Outcomes in Risdiplam-Treated Male Patients with Spinal Muscular Atrophy: A Multicenter Case Series. (PubMed, Adv Ther) - "This series presents three cases of successful conception while a male patient was receiving risdiplam, a US Food and Drug Administration-approved treatment for SMA. Although there were reproductive concerns due to impairment in spermatogenesis that arose during nonclinical studies, this case series demonstrates that there was sufficient sperm production while on risdiplam to result in pregnancy. More research is needed to provide a complete understanding of the effects of risdiplam on male fertility in humans. Graphical abstract available for this article."

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

Chugai Obtains Regulatory Approval for First Tablet for SMA, Evrysdi (Chugai Press Release) - "Chugai Pharmaceutical Co., Ltd...announced today that it has obtained regulatory approval from the Ministry of Health, Labour and Welfare for 'Evrysdi Tablets 5mg,' a new formulation of the spinal muscular atrophy (SMA) treatment Evrysdi [generic name: risdiplam]. Evrysdi is currently the only orally administered treatment for SMA. While the currently available dry syrup can be taken regardless of age and weight, the newly approved tablet formulation provides an additional option for people with SMA who are 2 years of age or older and weigh 20 kg or more...This approval is based on a bioequivalence study conducted by Roche. The study confirmed that the 5 mg tablet, when swallowed whole, provides comparable exposure to the existing dry syrup formulation."

Japan approval • Muscular Atrophy

MANATEE: A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy (clinicaltrials.gov) - P2/3 | N=259 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Mar 2028 ➔ Feb 2029

Trial primary completion date • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

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

Roche to share latest scientific advancements from its neuromuscular portfolio at Muscular Dystrophy Association (MDA) 2025 conference (GlobeNewswire) - P2 | N=231 | SUNFISH (NCT02908685) | Sponsor: Hoffmann-La Roche | "Five-year exploratory data from the pivotal SUNFISH study of Evrysdi in people with Types 2 or 3 SMA...SMA patients on Evrysdi demonstrated overall long-term stabilisation of motor function improvements from baseline that were observed during the first year, as measured by Motor Function Measure 32 (MFM-32)....Patients (>12 years of age) and caregivers both reported continuous improvement or stabilization in levels of independence for performing daily activities, such as dressing, picking up objects and washing, as measured by the SMA Independence Scale (SMAIS-ULM)."

P2 data • Muscular Atrophy

Risdiplam: Therapeutic Effects and Tolerability in a Small Cohort of 6 Adult Type 2 and Type 3 SMA Patients (AAN 2025) - "Two patients previously treated with Nusinersen maintained the pre-Risdiplam scores. Risdiplam was well -tolerated and resulted in improvement or stabilization of motor functions. MFM32 proved to be sensitive to detect changes induced by therapy. Subjective meaningful improvements were sustained overtime especially in bulbar functions, breath fatigue and distal motor abilities."

Clinical • Fatigue

Safety and Efficacy of Disease-modifying Therapies in Spinal Muscular Atrophy: A Systematic Review and Network Meta-analysis (AAN 2025) - "Nusinersen and OAX significantly improve motor milestones and survival in SMA, while OAX achieves a higher response in motor milestones. Risdiplam elevates SMN protein levels but does affect survival."

Retrospective data • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Clinical Outcomes of Adult Spinal Muscular Atrophy Patients on Appropriate Pharmaceutical Interventions: A Retrospective Chart Review (AAN 2025) - "Nusinersen and risdiplam lead to improvements or maintenance in functional status for adults with SMA, offering significant benefit."

Clinical data • Retrospective data • Review • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases • SMA4 • SMN1 • SMN2

Two Cases of Adhesive Arachnoiditis Following Intrathecal Nusinersen (AAN 2025) - "Although arachnoiditis is rarely associated with SMA, this unfavorable outcome should be considered when prescribing IT therapies. Both patients reported here had spinal fusions before starting nusinersen. The incidence of post-spinal fusion arachnoid adhesions is unknown but is a likely contributing factor in both cases."

Clinical • Anesthesia • CNS Disorders • Inflammation • Pain • Urology

Stem Cell-Derived Spinal Cord Organoid Model: Temporal and Cell-Specific Analysis of Molecular Effects of a Risdiplam Analogue (AAN 2025) - "Stem cell-derived spinal cord organoids prove to be a valuable tool for studying SMA treatments in a human proxy model. This model offers a robust platform for identifying complementary pharmacological targets within an extended therapeutic window, potentially improving future treatment strategies for SMA."

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

SAPPHIRE: Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam (clinicaltrials.gov) - P3 | N=188 | Completed | Sponsor: Scholar Rock, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Genetic Disorders • Movement Disorders • Muscular Atrophy • Rare Diseases

Spinal muscular atrophy type 3 and treatment adherence in a changing therapeutic landscape: a national-center experience. (PubMed, Croat Med J) - "Nusinersen had a positive treatment effect despite missed doses during the COVID-19 pandemic. Although the most significant improvements can be expected in patients treated the earliest, nusinersen treatment can be beneficial even in long-standing SMA."

Journal • CNS Disorders • Genetic Disorders • Infectious Disease • Movement Disorders • Muscular Atrophy • Novel Coronavirus Disease • Rare Diseases

WeSMA: Long-term Follow-up Study of Risdiplam in Participants With Spinal Muscular Atrophy (SMA) (clinicaltrials.gov) - P4 | N=402 | Active, not recruiting | Sponsor: Genentech, Inc. | Recruiting ➔ Active, not recruiting

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

Sensory Nerve Action Potential Analysis in a Cohort of Patients With Spinal Muscular Atrophy Aged 12 Years and Older. (PubMed, Muscle Nerve) - "Our findings suggest the preserved sensory integrity of the median nerve in the majority of patients with SMA (94%), even in longstanding disease. The resilience of sensory neurons of the median nerve, and whether this extends to other peripheral nerves, warrants further investigation."

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

Early Treatment in Preterm Twins With Spinal Muscular Atrophy. (PubMed, J Child Neurol) - "They were treated with risdiplam followed by onasemnogene abeparvovec at a gestational age of 35 and 43 weeks, respectively. This case adds to the limited data on treatment options for preterm infants."

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