Subject(s)
Confidentiality , Drug Costs , Drug Industry , Evidence-Based Medicine/standards , State Medicine/standards , Cardiovascular Agents/economics , Cardiovascular Agents/therapeutic use , Cost-Benefit Analysis , Humans , RNA, Small Interfering/economics , RNA, Small Interfering/therapeutic use , United KingdomABSTRACT
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.
Subject(s)
Amyloid Neuropathies, Familial/therapy , Benzoxazoles/administration & dosage , Cost of Illness , Oligonucleotides/administration & dosage , RNA, Small Interfering/administration & dosage , Amyloid Neuropathies, Familial/economics , Benzoxazoles/economics , Drug Costs/statistics & numerical data , Health Care Costs/statistics & numerical data , Hospitalization/economics , Humans , Oligonucleotides/economics , RNA, Small Interfering/economics , SpainABSTRACT
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.
Subject(s)
Anticholesteremic Agents/therapeutic use , Hypercholesterolemia/drug therapy , PCSK9 Inhibitors , RNA, Small Interfering/therapeutic use , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Anticholesteremic Agents/administration & dosage , Anticholesteremic Agents/economics , Cholesterol, LDL/blood , Clinical Trials as Topic , Drug Administration Schedule , Drug Costs , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/blood , Hypercholesterolemia/enzymology , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/drug therapy , Hyperlipoproteinemia Type II/enzymology , Medication Adherence , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/economicsABSTRACT
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.
Subject(s)
Amyloid Neuropathies, Familial/drug therapy , Oligodeoxyribonucleotides, Antisense/therapeutic use , Oligonucleotides/therapeutic use , Prealbumin/genetics , RNA, Small Interfering/therapeutic use , Amyloid Neuropathies, Familial/genetics , Cost-Benefit Analysis , Drug Costs , Genetic Therapy/economics , Genetic Therapy/legislation & jurisprudence , Genetic Therapy/methods , Humans , Oligodeoxyribonucleotides, Antisense/economics , Oligonucleotides/economics , RNA Interference , RNA, Small Interfering/economics , Treatment OutcomeABSTRACT
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.
Subject(s)
Amyloid Neuropathies, Familial/drug therapy , Genetic Therapy/economics , Oligodeoxyribonucleotides, Antisense/therapeutic use , Prealbumin/genetics , Quality-Adjusted Life Years , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/genetics , Cost-Benefit Analysis , Data Interpretation, Statistical , Drug Costs , Genetic Therapy/legislation & jurisprudence , Genetic Therapy/methods , Humans , Models, Economic , Oligodeoxyribonucleotides, Antisense/economics , Oligonucleotides/economics , Oligonucleotides/therapeutic use , RNA Interference , RNA, Small Interfering/economics , RNA, Small Interfering/therapeutic use , Randomized Controlled Trials as Topic , Treatment OutcomeSubject(s)
CRISPR-Cas Systems/genetics , Cooperative Behavior , Inventions/economics , Inventions/legislation & jurisprudence , Patents as Topic/legislation & jurisprudence , Academies and Institutes/economics , Academies and Institutes/legislation & jurisprudence , Licensure/economics , Ownership/economics , Prenatal Diagnosis/economics , RNA, Small Interfering/economics , RNA, Small Interfering/therapeutic use , Technology Transfer , Time Factors , Universities/economics , Universities/legislation & jurisprudenceSubject(s)
Antiviral Agents/therapeutic use , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Vaccines/therapeutic use , Adult , Aged , Antibodies, Monoclonal/economics , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/economics , Child , Child, Preschool , Commerce , Drug Design , Humans , Infant , RNA, Small Interfering/economics , RNA, Small Interfering/therapeutic use , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Vaccines/economicsSubject(s)
Antiviral Agents/therapeutic use , Genetic Therapy/methods , Herpes Genitalis/therapy , Herpesvirus 2, Human/genetics , RNA, Small Interfering/therapeutic use , Administration, Topical , Animals , Antiviral Agents/economics , Cost-Benefit Analysis , Female , Gene Silencing , Herpesvirus 2, Human/physiology , Humans , Mice , RNA Interference , RNA, Small Interfering/economics , Virus ReplicationABSTRACT
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.
Subject(s)
Hepatitis B virus/growth & development , Hepatitis B virus/genetics , RNA, Small Interfering/economics , RNA, Small Interfering/genetics , Virus Replication/genetics , Base Sequence , Carcinoma, Hepatocellular , Cell Line, Tumor , Cost-Benefit Analysis , Gene Expression Regulation, Viral , Green Fluorescent Proteins/genetics , Hepatitis B Surface Antigens/genetics , Hepatitis B e Antigens/genetics , Humans , Liver Neoplasms , Molecular Sequence Data , Plasmids/genetics , RNA/genetics , RNA, Double-Stranded/genetics , Ribonuclease III , TransfectionABSTRACT
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.