Assuntos
Sistemas CRISPR-Cas/genética , Comportamento Cooperativo , Invenções/economia , Invenções/legislação & jurisprudência , Patentes como Assunto/legislação & jurisprudência , Academias e Institutos/economia , Academias e Institutos/legislação & jurisprudência , Licenciamento/economia , Propriedade/economia , Diagnóstico Pré-Natal/economia , RNA Interferente Pequeno/economia , RNA Interferente Pequeno/uso terapêutico , Transferência de Tecnologia , Fatores de Tempo , Universidades/economia , Universidades/legislação & jurisprudênciaRESUMO
Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076 (inotersen), 427,250 (patisiran) and 129,737 (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954), followed by inotersen (308,358), and patisiran (458,771).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.
Assuntos
Neuropatias Amiloides Familiares/terapia , Benzoxazóis/administração & dosagem , Efeitos Psicossociais da Doença , Oligonucleotídeos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Neuropatias Amiloides Familiares/economia , Benzoxazóis/economia , Custos de Medicamentos/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Humanos , Oligonucleotídeos/economia , RNA Interferente Pequeno/economia , EspanhaRESUMO
INTRODUCTION: If statins are unsuccessful at achieving the LDL cholesterol level goal in subjects with hypercholesterolemia, non-statin therapy should be added to reduce cardiovascular morbidity and mortality. The first inhibitors of proprotein convertase substilisin-kexin type 9 (PCSK9) were human monoclonal antibodies and these reduced LDL cholesterol and cardiovascular events. Inclisiran is a small interfering RNA molecule (siRNAs) directed against PCSK9. AREAS COVERED: This key paper evaluation focuses on Phase 3 trials that assess inclisiran in the treatment of hypercholesterolemia and heterozygous familial hypercholesterolemia. EXPERT OPINION: To date, the findings with inclisiran have been very promising as it causes large decreases in LDL cholesterol with few adverse effects. However, there are some limitations to its widespread use. Firstly, cardiovascular outcomes trials have not been completed, so we do not know how inclisiran compares to the PCSK9 monoclonal antibodies, which, seem to me, to only have a modest effect on cardiovascular outcomes. Secondly, a major problem with the PCSK9 monoclonal antibodies is that they are expensive, and their use is often discontinued or not pursued, which can leave the subjects intended for treatment at high cardiovascular risk. At present, it is not clear whether similar problems around cost will apply to inclisiran.
Assuntos
Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Inibidores de PCSK9 , RNA Interferente Pequeno/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/economia , LDL-Colesterol/sangue , Ensaios Clínicos como Assunto , Esquema de Medicação , Custos de Medicamentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/enzimologia , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/enzimologia , Adesão à Medicação , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/economiaRESUMO
DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP, Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Mickle, Dreitlein, and Pearson are ICER employees. Lasser, Cipriano, and Hoch have nothing to disclose.
Assuntos
Neuropatias Amiloides Familiares/tratamento farmacológico , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos/uso terapêutico , Pré-Albumina/genética , RNA Interferente Pequeno/uso terapêutico , Neuropatias Amiloides Familiares/genética , Análise Custo-Benefício , Custos de Medicamentos , Terapia Genética/economia , Terapia Genética/legislação & jurisprudência , Terapia Genética/métodos , Humanos , Oligodesoxirribonucleotídeos Antissenso/economia , Oligonucleotídeos/economia , Interferência de RNA , RNA Interferente Pequeno/economia , Resultado do TratamentoRESUMO
DISCLOSURES: No funding support was received for the writing of this commentary. The author ser ves as a consultant for Akcea Therapeutics, Alnylam Phar maceuticals, Corino Therapeutics, Intellia Therapeutics, and Ionis Pharmaceuticals.
Assuntos
Neuropatias Amiloides Familiares/tratamento farmacológico , Terapia Genética/economia , Oligodesoxirribonucleotídeos Antissenso/uso terapêutico , Pré-Albumina/genética , Anos de Vida Ajustados por Qualidade de Vida , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/genética , Análise Custo-Benefício , Interpretação Estatística de Dados , Custos de Medicamentos , Terapia Genética/legislação & jurisprudência , Terapia Genética/métodos , Humanos , Modelos Econômicos , Oligodesoxirribonucleotídeos Antissenso/economia , Oligonucleotídeos/economia , Oligonucleotídeos/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/economia , RNA Interferente Pequeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Small interfering RNAs (siRNAs) are powerful RNA interference (RNAi) reagents for directed post- transcriptional gene silencing. Exogenous siRNA is frequently used in RNAi studies. However, due to profound differences in the activity of siRNAs targeted to different regions of a gene, several reagents may have to be screened for optimal activity. This approach is expensive due to the cost of chemical synthesis of RNAs. We report a technically simple, quick and cost-effective method for the production of siRNAs that makes use of in vitro transcription and deoxyribozyme digestion of the transcripts to produce the desired sequence and length. The method allows for several siRNAs to be produced in parallel at much reduced costs. The siRNAs produced with this method were tested in MDA-MB-231 human breast cancer cells for efficacy against the type 1 insulin-like growth factor receptor (IGF1R) mRNA and they caused dose-dependent inhibition of IGF1R expression comparable to that induced by chemically synthesised siRNAs of the same sequence. This method is also useful for producing long RNA fragments of defined length and sequence that may be difficult to synthesise chemically, and also for producing large quantities of RNAs for applications including structural studies and the study of interactions between RNA and other molecules, such as proteins, other nucleic acids and drugs.
Assuntos
Interferência de RNA , RNA Interferente Pequeno/síntese química , Análise Custo-Benefício , Regulação da Expressão Gênica , Humanos , Métodos , RNA Interferente Pequeno/economia , RNA Interferente Pequeno/genética , Receptor IGF Tipo 1/genética , Transfecção , Células Tumorais CultivadasAssuntos
Confidencialidade , Custos de Medicamentos , Indústria Farmacêutica , Medicina Baseada em Evidências/normas , Medicina Estatal/normas , Fármacos Cardiovasculares/economia , Fármacos Cardiovasculares/uso terapêutico , Análise Custo-Benefício , Humanos , RNA Interferente Pequeno/economia , RNA Interferente Pequeno/uso terapêutico , Reino UnidoRESUMO
AIM: To find a cost-effective method of preparation of short interfering RNAs based on cloning, fermentation, digestion and purification (CFDP) and test its feasibility to inhibit hepatitis B virus replication in cell culture. METHODS: We constructed an expression vector containing T7 and tac promoter in a head-to-head orientation. cDNA fragment of interest was cloned into this vector between the opposing promoters. dsRNAs were expressed with this vector in Escherichia coli, and purified by affinity chromatography using CF 11 column. They were digested by RNase III in a buffer containing manganese ions, then separated on 15% non-denaturing PAGE, and the siRNAs about 25 bp in length were recovered. siRNAs prepared with CFDP were co-transfected with target gene expression plasmid into human cell lines with lipofectamine 2,000 to test their inhibition efficiency. RESULTS: siRNAs corresponding to part of the hepatitis B virus polymerase gene (siHBVP) prepared by CFDP specifically and dramatically suppressed the virus protein expression. The HBsAg expression level was reduced to 10% that of the control by co-transfection of 60 nmol/L siHBVP in SMMC7721 cells. Dose-dependent effect on suppression of HBsAg and HBeAg expression was observed in HepG2 cells. The highest inhibition rate was kept at 70% during the six days after transfection of 7.5 nmol/L siHBVP. CONCLUSION: We show CFDP is a very promising method to prepare therapeutic agents in anti-virus applications.