TY - JOUR
T1 - Breaking the chains of lipoprotein lipase deficiency
T2 - A pediatric perspective on the efficacy and safety of Volanesorsen
AU - den Hollander, Bibiche
AU - Brands, Marion M
AU - Nijhuis, Ilse J M
AU - Doude van Troostwijk, Lous J A E
AU - van Essen, Peter
AU - Hofsteenge, Ageeth H
AU - Koot, Bart G
AU - Müller, Annelieke R
AU - Tseng, Laura A
AU - Stroes, Erik S G
AU - van de Ven, Peter M
AU - Wiegman, Albert
AU - van Karnebeek, Clara D M
N1 - Publisher Copyright: © 2024
PY - 2024/5
Y1 - 2024/5
N2 - RATIONALE: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency.METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions.RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life.CONCLUSION: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.
AB - RATIONALE: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency.METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions.RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life.CONCLUSION: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.
KW - Hypertriglyceridemia
KW - Lipoprotein lipase deficiency
KW - Lipoprotein lipase mutation
KW - Pancreatitis
KW - Pediatrics
KW - Volanesorsen
UR - http://www.scopus.com/inward/record.url?scp=85186097923&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2024.108347
DO - 10.1016/j.ymgme.2024.108347
M3 - Article
C2 - 38401382
SN - 1096-7192
VL - 142
SP - 108347
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1
M1 - 108347
ER -