VAL-1221 / Valerion - LARVOL DELTA

MicroLC-HRMS selective quantification of a biotherapeutic fusion protein in plasma and cerebrospinal fluid of patients with Lafora disease using a linker-containing signature peptide. (PubMed, J Pharm Biomed Anal) - "Applied to compassionate-use samples from five patients with Lafora disease receiving intravenous VAL-1221 (20 mg/kg every other week), VAL-1221 was detected in plasma up to 4 h post-infusion, whereas cerebrospinal fluid concentrations were below the method detection limit under the tested regimen. Overall, this workflow provides a validated, sequence-specific approach for exposure and biodistribution assessment of fusion-protein biotherapeutics in human matrices."

Journal

A Single-Kindred Cluster of Val122Ile Transthyretin Amyloid Cardiomyopathy: Subclinical Case Series of Three Japanese Patients. (PubMed, Intern Med) - "The transthyretin Val122Ile variant is associated with poor clinical outcomes. Clinicians should be aware that this variant can also be sporadically present in elderly Japanese patients with cardiomyopathy or heart failure."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

New therapeutic strategies for Lafora disease: Evaluation of the safety, efficacy, pharmacokinetics and metabolomic profile of intravenous VAL-1221 treatment. (PubMed, Neurotherapeutics) - "These findings demonstrate that intravenous VAL-1221 is safe but ineffective, providing an important negative result that prevents further patient exposure to this approach and redirects efforts toward direct central nervous system delivery methods. The study also demonstrates the feasibility of assessing disease progression using clinical and neuroimaging measures, providing a valuable framework for clinical trials in LD."

Journal • PK/PD data • CNS Disorders • Dermatology • Epilepsy • Hypotension • Metabolic Disorders • Movement Disorders

VAL-1221 for the treatment of patients with Lafora disease: study protocol for a single-arm, open-label clinical trial. (PubMed, BMJ Open) - P2 | "The results of this study will be disseminated by the investigators through presentations at international scientific conferences and reported in peer-reviewed scientific journals. European Union Clinical Trials Register (EudraCT 2023-000185-34)."

Clinical • Clinical protocol • Journal • CNS Disorders • Epilepsy • Movement Disorders • Pediatrics • Pompe Disease • EPM2A

Enzyme replacement therapy for late-onset Pompe disease. (PubMed, Cochrane Database Syst Rev) - "One trial compared the effect of ERT to placebo in LOPD, showing that alglucosidase alfa probably improves 6MWT and respiratory function (both moderate-certainty evidence). Avalglucosidase alfa probably improves 6MWT compared with alglucosidase alfa (moderate-certainty evidence). Cipaglucosidase plus miglustat probably improves FVC compared to alglucosidase alfa plus placebo (moderate-certainty evidence). Other trials studied the adjunct effect of clenbuterol and albuterol along with alglucosidase alfa, with little to no evidence of benefit. No significant rise in adverse events was noted with all ERTs. The impact of ERT on some outcomes remains unclear, and longer RCTs are needed to generate relevant information due to the progressive nature of LOPD. Alternative resources, such as post-marketing registries, could capture some of this information."

Journal • Review • Fatigue • Metabolic Disorders • Pompe Disease

VAL-1221: A Phase II Candidate for Lafora Disease (AES 2023) - P1/2 | "VAL-1221 is a promising therapeutic candidate for Lafora disease and other related PGDs. The development of joint safety and efficacy databases from ongoing treatments will be very informative as more pivotal studies are initiated. Future research detection of VAL-1221 in treated patient CSF and combined analysis of plasma and CSF metabolic biomarkers will seek to further establish on-target mechanism of action."

P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Epilepsy • Targeted Protein Degradation

LEAP: Intravenous VAL-1221 Lafora Expanded Access Protocol (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: Parasail, LLC

New trial