Pediatric experience with mipomersen as adjunctive therapy for homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited condition resulting in severely elevated low-density lipoprotein cholesterol levels (LDL-C) leading to premature cardiovascular disease and, often, death. Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B (apo B) synthesis, lowering LDL-C levels. Mipomersen has demonstrated efficacy in adult HoFH patients, possibly providing a therapeutic option for pediatric patients. Study objectives were to summarize mipomersen efficacy and safety in the pediatric cohort of a phase 3 randomized controlled trial (RCT) and subsequent open-label extension study (OLE). METHODS: Seven patients aged 12-18 years were randomized to 200-mg mipomersen or placebo weekly (26 weeks) and received mipomersen in the OLE (52 or 104 weeks). Plasma LDL-C and apo B concentrations and adverse events were assessed. RESULTS: All pediatric patients completed the RCT and entered OLE. The 3 mipomersen patients in the RCT experienced mean reductions from baseline to RCT end of 42.7% and 46.1% for LDL-C and apo B, respectively. Of the 4 placebo patients, 3 responded well to mipomersen during OLE, with reductions in LDL-C of 26.5%-42.1%. Three patients completed OLE treatment, and 4 patients discontinued therapy due to adverse events. Lipid level fluctuations were observed and were likely due to poor compliance. CONCLUSIONS: Long-term mipomersen treatment was successful regarding efficacy parameters for pediatric HoFH patients. The safety profile was consistent with other phase 3 clinical trials. Long-term compliance was an issue. Measures supporting adherence should be encouraged.

Significant gaps in awareness of familial hypercholesterolemia among physicians in selected Asia-Pacific countries: a pilot study.

BACKGROUND: Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by high plasma cholesterol levels and a very high risk of early heart disease. The prevalence of FH is estimated to be at least 1:500, with at least 3.6 million individuals in the Asia-Pacific region. OBJECTIVE: To assess awareness, knowledge, and perception of FH among practicing physicians in Japan, South Korea, and Taiwan. METHODS: Physicians from 3 economically developed Asian countries were requested to anonymously complete a structured Internet-based survey regarding FH. This survey sought responses on the clinical description, inheritance, prevalence, cardiovascular disease risk, practices, and opinions on screening. RESULTS: Of 230 physicians surveyed, 47% were aware of the heritability, 27% of the prevalence, and 13% of the risk of cardiovascular disease relating to FH. The majority (70%) perceived themselves to have an above-moderate familiarity with FH. Primary care physicians (59%) and lipid specialists (41%) were perceived as the best providers for caring for FH, including cascade screening services, with a lesser role perceived for cardiologists, endocrinologists, and no significant role for nursing staff. Only 35% of physicians were aware of specialist clinical services for lipid disorders in their geographic area. CONCLUSION: Extensive education and training programs are required to complement the implementation of region-specific models of care for FH in Asia. Further enhancement of existing lipid services and facilities are also warranted to optimise service models.

Cost and clinical analysis of autologous hematopoietic stem cell mobilization with G-CSF and plerixafor compared to G-CSF and cyclophosphamide.

Plerixafor plus granulocyte-colony stimulating factor (G-CSF) has been shown to mobilize more CD34(+) cells than G-CSF alone for autologous hematopoietic stem cell transplantation (HSCT). However, many centers use chemotherapy followed by G-CSF to mobilize CD34(+) cells prior to HSCT. We performed a retrospective study of patients who participated in the expanded access program (EAP) of plerixafor and G-CSF for initial mobilization of CD34(+) cells, and compared outcomes to matched historic controls mobilized with cyclophosphamide 3-5 g/m(2) and G-CSF at 2 centers that participated in the EAP Control patients were matched for age, sex, disease, disease stage, and number of prior therapies. Mobilization costs were defined to be the costs of medical procedures, resource utilization, and medications. Median national CMS reimbursement rates were used to establish the costs of procedures, hospitalization, provider visits, apheresis, CD34(+) cell processing and cryopreservation. Average sale price was used for G-CSF, plerixafor, cyclophosphamide, MESNA, antiemetics, and antimicrobials. A total of 33 patients from the EAP and 33 matched controls were studied. Two patients in the control group were hospitalized for neutropenic fever during the mobilization period. Apheresis started on the scheduled day in 33 (100%) study patients and in 29 (88%) control patients (P = 0.04). Sixteen (48%) control patients required weekend apheresis. There was no difference in number of CD34(+) cells collected between the groups, and all patients proceeded to HSCT with no difference in engraftment outcomes. Median total cost of mobilization was not different between the plerixafor/G-CSF and control groups ($14,224 versus $18,824; P = .45). In conclusion, plerixafor/G-CSF and cyclophosphamide/G-CSF for upfront mobilization of CD34(-) cells resulted in similar numbers of cells collected, costs of mobilization, and clinical outcomes. Additionally, plerixafor/G-CSF mobilization resulted in more predictable days of collection, no weekend apheresis procedures, and no unscheduled hospital admissions.