Pombiliti (cipaglucosidase alfa-atga) / Amicus - LARVOL DELTA

Evaluating PICOs Requested by Member States During Scoping for EU HTA Versus Those Covered in Actual HTAs (ISPOR 2025) - "We aimed to assess the alignment between PICOs identified in EUnetHTA 21 scoping surveys for PLUVICTO®, EBVALLO® and POMBILITI™ published in 2023, versus PICOs considered in actual HTAs of these products. Published HTAs for PLUVICTO, EBVALLO and POMBILITI conducted to date (January 6, 2025) were identified and reviewed. PICOs included in actual HTAs were predicted by the EUnetHTA 21 scoping exercise; however, there may be over-scoping of PICOs due to the scoping process and requirement to meet all member states' needs. This may place an unnecessary burden on manufacturers responding to irrelevant PICOs and manufacturer input into the scoping of EU JCAs could be beneficial"

A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With LOPD (clinicaltrials.gov) - P3 | N=119 | Completed | Sponsor: Amicus Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Dec 2024

Trial completion • Trial completion date • Pompe Disease

Amicus Therapeutics Announces Full-Year 2024 Financial Results and Corporate Updates (GlobeNewswire) - "Galafold (migalastat) net product sales for the full-year 2024 were $458.1 million, representing a year-over-year increase of 18%, or 19% at CER. Fourth quarter net product sales were $127.5 million...Pombiliti (cipaglucosidase alfa-atga) + Opfolda (miglustat) net product sales for the full-year 2024 were $70.2 million. Fourth quarter net product sales were $22.2 million...For the full year 2025, the Company provides revenue growth guidance for Pombiliti + Opfolda of +65% to +85% on a constant currency basis (CER)...First commercial patients from these countries are anticipated to begin treatment over the first half of 2025. Additionally, Pombiliti + Opfolda received regulatory approval in Australia and the Company anticipates new regulatory decisions in Canada and Japan in 2025 as well as additional reimbursement agreements throughout the year."

Canada approval • Japan approval • Reimbursement • Sales • Fabry Disease • Pompe Disease

Effect Size Analysis of Cipaglucosidase Alfa Plus Miglustat Versus Alglucosidase Alfa in ERT-experienced Adults with Late-onset Pompe Disease in PROPEL (S21.003). (PubMed, Neurology) - P3 | "The randomized, double-blind PROPEL study (ATB200-03; NCT03729362) compared the efficacy and safety of the investigational two-component enzyme replacement therapy (ERT) cipa+mig with alg plus placebo in adults with late-onset Pompe disease (LOPD); 77% of patients had received ERT with alg before study entry (median ERT duration 7.4 years)...Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio...Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH."

Clinical • Journal • CNS Disorders • Fatigue • Muscular Dystrophy • Pompe Disease • Rare Diseases

A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With LOPD (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Amicus Therapeutics | Trial completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Pompe Disease

Challenges in multinational rare disease clinical studies during COVID-19: regulatory assessment of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease. (PubMed, J Neurol) - P3 | "PROPEL (ATB200-03; NCT03729362) compared the efficacy and safety of cipaglucosidase alfa plus miglustat (cipa + mig), a two-component therapy for late-onset Pompe disease (LOPD), versus alglucosidase alfa plus placebo (alg + pbo). Both statistical analysis approaches led to similar results and consistent conclusions, confirming the efficacy of cipa + mig for adults with LOPD. NCT03729362; trial start date: December 4, 2018.Trial registration number."

Journal • Infectious Disease • Lysosomal Storage Diseases • Metabolic Disorders • Novel Coronavirus Disease • Pompe Disease • Rare Diseases

Indirect Treatment Comparison (ITC) of Avalglucosidase Alfa (AVA) vs Cipaglucosidase Alfa Plus Miglustat (Cipa+mig) in Late-Onset Pompe Disease (LOPD): An Updated Analysis Using Mixed-Model Repeated Measures (MMRM) Data (ISPOR-EU 2024) - P1, P1/2, P2, P3 | " The analysis of enzyme replacement therapy (ERT)-naïve patients used individual patient data (IPD) from the Phase 3 COMET trial (AVA, n =51; alglucosidase alfa, n =49) and aggregate data from the Phase 3 PROPEL trial (Cipa+mig, n =27). The analysis of ERT-experienced patients compared IPD from the COMET open-label extension and NEO-1 (NCT01898364)/NEO-EXT (NCT02032524) studies (AVA, n =59) vs aggregate data from the PROPEL and ATB200-02 (NCT02675465, Cohorts I and IV) studies (Cipa+mig, n =81)... Using the same MMRM analysis across different data sources, AVA demonstrated favorable respiratory function and mobility outcomes in patients with LOPD. The data are consistent and more favorable for AVA compared to the previous ITC analyses, with statistically significant results in treatment-naïve patients, and further support the comparative efficacy of AVA vs Cipa+mig."

Pompe Disease

Pompe disease: Unmet needs and emerging therapies. (PubMed, Mol Genet Metab) - "The approval of avalglucosidase alfa (Nexviazyme®) and cipaglucosidase alfa (Pombiliti®) with miglustat (Opfolda®) represents a new generation of enzyme replacement therapies seeking to further improve patient outcomes beyond alglucosidase alfa. Key treatments include tissue-targeted enzyme replacement therapy, which seeks to enhance enzyme concentration in target tissues such as the central nervous system; substrate reduction therapy, which reduces intracellular glycogen concentrations via novel mechanisms; and gene therapy, which may restore endogenous production of deficient acid alpha-glucosidase. Each of these proposed treatments shows promise as a future therapeutic option to improve quality of life in Pompe disease by more efficiently treating the underlying cause of disease progression: glycogen accumulation."

Journal • Review • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Pombiliti and Opfolda: shaping the future of adult late-onset pompe disease: an editorial. (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal • Pompe Disease

Health-Related Quality-of-Life Utility Values in Adults With Late-Onset Pompe Disease: Analyses of EQ-5D Data From the PROPEL Clinical Trial. (PubMed, J Health Econ Outcomes Res) - P3 | "PROPEL was a Phase 3, double-blind, randomized controlled trial, which evaluated cipaglucosidase alfa plus miglustat, vs alglucosidase alfa plus placebo in 123 adult patients with LOPD (clinicaltrials.gov: NCT03729362)... Overall, the results from our analysis indicate that important HRQoL losses are associated with reductions in mobility and respiratory function for patients with Pompe disease. The study provides important evidence of HRQoL utility values for patients with advanced LOPD, a population for whom published data are limited."

HEOR • Journal • Fatigue • Lysosomal Storage Diseases • Metabolic Disorders • Pain • Pompe Disease • Rare Diseases

First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221 (clinicaltrials.gov) - P1/2 | N=32 | Completed | Sponsor: Amicus Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Pompe Disease

Regulatory news: Cipaglucosidase alfa-atga (Pombiliti) coadministered with Miglustat (Opfolda) for adults with late-onset Pompe disease. (PubMed, J Inherit Metab Dis) - No abstract available

Journal • Pompe Disease

First-In-Human Study to Evaluate Safety, Tolerability, and PK of Intravenous ATB200 Alone and When Co-Administered With Oral AT2221 (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: Amicus Therapeutics | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Pompe Disease

Effect Size Analysis of Cipaglucosidase Alfa Plus Miglustat Versus Alglucosidase Alfa in ERT-experienced Adults with Late-onset Pompe Disease in PROPEL (AAN 2024) - P3 | "Objective:To analyze within-group effect sizes of cipaglucosidase alfa plus miglustat (cipa+mig) and alglucosidase alfa (alg) for efficacy, quality of life (QoL), and biomarker variables in ERT-experienced patients.Background:The randomized, double-blind PROPEL study (ATB200-03; NCT03729362) compared the efficacy and safety of the investigational two-component enzyme replacement therapy (ERT) cipa+mig with alg plus placebo in adults with late-onset Pompe disease (LOPD); 77% of patients had received ERT with alg before study entry (median ERT duration 7.4 years). This analysis shows that ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements in a number of outcomes, highlighting the potential of cipa+mig to become an important treatment option for these patients. Sponsored by Amicus Therapeutics Inc."

Clinical • Fatigue • Pompe Disease

A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With LOPD (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: Amicus Therapeutics | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Pompe Disease

Switching treatment to cipaglucosidase alfa+miglustat positively affects motor function and quality of life in patients with late-onset Pompe disease (ACMG 2024) - P3 | "The Phase III PROPEL trial (NCT03729362) assessed efficacy and safety of the novel, two-component therapy cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in adults with LOPD. These analyses highlight the patient perspective and provide evidence that switching from alg+pbo to cipa+mig benefits patients' motor function and HRQoL."

Clinical • HEOR • Pompe Disease

A Global Prospective Observational Registry of Patients With Pompe Disease (clinicaltrials.gov) - P=N/A | N=500 | Recruiting | Sponsor: Amicus Therapeutics | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2033 ➔ Dec 2034 | Trial primary completion date: Nov 2033 ➔ Dec 2034

Enrollment open • Trial completion date • Trial primary completion date • Pompe Disease

104-week efficacy and safety of cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease: a phase III open-label extension study (ATB200-07). (PubMed, J Neurol) - P3 | "The phase III double-blind PROPEL study compared the novel two-component therapy cipaglucosidase alfa + miglustat (cipa + mig) with alglucosidase alfa + placebo (alg + pbo) in adults with late-onset Pompe disease (LOPD). No new safety signals were identified. Cipa + mig treatment up to 104 weeks was associated with overall maintained improvements (6MWD, biomarkers) or stabilization (FVC) from baseline with continued durability, and was well tolerated, supporting long-term benefits for patients with LOPD.Trial registration number: NCT04138277; trial start date: December 18, 2019."

Journal • P3 data • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Switching treatment to cipaglucosidase alfa+miglustat positively affects motor function and quality of life in patients with late-onset Pompe disease (MDA 2024) - P3 | "The Phase III PROPEL trial (NCT03729362) assessed efficacy and safety of the novel, two-component therapy cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in adults with LOPD. These analyses highlight the patient perspective and provide evidence that switching from alg+pbo to cipa+mig benefits patients’ motor function and HRQoL."

Clinical • HEOR • Pompe Disease

Switching treatment to cipaglucosidase alfa+miglustat positively affects motor function and quality of life in patients with late-onset Pompe disease (MDA 2024) - No abstract available

Clinical • HEOR • Pompe Disease

Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02). (PubMed, J Neurol) - P1/2 | "Overall, cipa + mig was well tolerated with a safety profile like alglucosidase alfa. ATB200-02 results show the potential benefits of cipa + mig as a long-term treatment option for Pompe disease. Trial registration number: NCT02675465 January 26, 2016."

Journal • P1/2 data • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

A Global Prospective Observational Registry of Patients With Pompe Disease (clinicaltrials.gov) - P=N/A | N=500 | Not yet recruiting | Sponsor: Amicus Therapeutics

New trial • Pompe Disease

A Comparison of Health State Occupancy Between Cipaglucosidase Alfa/Miglustat and Alglucosidase Alfa Within a Cost-Effectiveness Modelling Analysis of Late-Onset Pompe Disease (ISPOR-EU 2023) - "Based on economic model, CIPA is estimated to delay disease progression, leading to reductions in the requirement for ambulatory and respiratory support. However, further research is required to inform the impact of CIPA on long-term progression"

Cost effectiveness • HEOR • Pompe Disease • Respiratory Diseases

Effect size analysis of cipaglucosidase alfa + miglustat versus alglucosidase alfa in ERT-experienced adults with late-onset Pompe disease in PROPEL (SSIEM 2023) - P3 | "Patients switching to cipa+mig did not demonstrate any significant within-group worsening and showed significant improvements for 6-minute walk distance (absolute and % predicted); upper, lower and overall manual muscle test; PROMIS fatigue; physician and subject global impression of change (5 of 8 subdomains); CK and Hex4 levels. Conclusions This analysis shows that ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements in a number of outcomes, highlighting the potential of cipa+mig to become an important treatment option for these patients."

Clinical • Fatigue • Pompe Disease

104-week efficacy and safety of cipaglucosidase alfa+miglustat in patients with late-onset Pompe disease previously treated with alglucosidase alfa (SSIEM 2023) - P3 | "No new safety signals were identified. Conclusions These data show that switching treatment from alg to cipa+mig was associated with a durable effect up to 104 weeks and was well tolerated, supporting long-term benefits of cipa+mig treatment for patients with LOPD."

Clinical • Fatigue • Pompe Disease