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Sensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene. We identified eight unrelated families from the eastern Chinese population carrying a founder variant c.41A>G (p.Lys14Arg) within COX20 in either a homozygous or compound heterozygous state. All patients displayed sensory ataxia with a decrease in non-length-dependent sensory potentials. COX20 encodes a key transmembrane protein implicated in the assembly of mitochondrial complex IV. We showed that COX20 variants lead to reduction of COX20 protein in patient's fibroblasts and transfected cell lines, consistent with a loss-of-function mechanism. Knockdown of COX20 expression in ND7/23 sensory neuron cells resulted in complex IV deficiency and perturbed assembly of complex IV, which subsequently compromised cell spare respiratory capacity and reduced cell proliferation under metabolic stress. Consistent with mitochondrial dysfunction in knockdown cells, reduced complex IV assembly, enzyme activity and oxygen consumption rate were also found in patients' fibroblasts. We speculated that the mechanism of COX20 was similar to other causative genes (e.g. SURF1, COX6A1, COA3 and SCO2) for peripheral neuropathies, all of which are functionally important in the structure and assembly of complex IV. Our study identifies a novel causative gene for the autosomal recessive sensory neuronopathy, whose vital function in complex IV and high expression in the proprioceptive sensory neuron further underlines loss of COX20 contributing to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease. [ABSTRACT FROM AUTHOR]

The United States relies primarily on market forces to determine prices for drugs, whereas most other industrialized countries use a variety of approaches to determine drug prices. Branded drug companies have patents and market exclusivity periods in most industrialized countries. During this period, pharmaceutical companies are allowed to set their list price as high as they prefer in the United States owing to the absence of government price control mechanisms that exist in other countries. Insured patients often pay a percentage of the list price, and cost sharing creates some pressure to lower the list price. Pharmacy benefit managers negotiate with drug companies for lower prices by offering the drug company favorable formulary placement and fewer utilization controls. However, these approaches appear to be less effective, compared with other countries' approaches to containing branded drug prices, because prices are substantially higher in the United States. Other industrialized countries employ various forms of rate setting and price regulation, such as external reference pricing, therapeutic valuation, and health technology assessment to determine the appropriate price. [ABSTRACT FROM AUTHOR]

Importance: Although independent charity patient assistance programs improve patient access to costly prescription drugs, recent federal investigations have raised questions about their potential to increase pharmaceutical spending and to violate the federal Anti-Kickback Statute. Little is known about the design of the programs, patient eligibility, or drug coverage.Objective: To examine the eligibility criteria of the independent charity patient assistance programs and the drugs covered by them.Design, Setting, and Participants: Descriptive cross-sectional study of the 6 largest independent charities offering patient assistance programs for patients including, but not limited to, Medicare beneficiaries in 2018. These charities offered 274 different disease-specific patient assistance programs. Drugs were identified for subgroup analysis that had any use reported on the Medicare Part D spending dashboard and any off-patent brand-name drugs that incurred more than $10 000 in Medicare spending per beneficiary in 2016.Exposures: Support by independent charity patient assistance programs.Main Outcomes and Measures: The primary outcomes were the characteristics of patient assistance programs, including assistance type, insurance coverage (vs uninsured), and income eligibility. The secondary outcomes were the cost of the drugs covered by the patient assistance programs and the coverage of expensive off-patent brand-name drugs vs substitutable generic drugs.Results: Among the 6 independent charity foundations included in the analysis, their total revenue in 2017 ranged from $24 million to $532 million, and expenditures on patient assistance programs ranged from $24 million to $353 million, representing on average, 86% of their revenue. Of the 274 patient assistance programs offered by these organizations, 168 (61%) provided only co-payment assistance, and the most common therapeutic area covered was cancer or cancer treatment-related symptoms (113 patient assistance programs; 41%). A total of 267 programs (97%) required insurance coverage as an eligibility criterion (ie, excluded uninsured patients). The most common income eligibility limit was 500% of the federal poverty level. The median annual cost of the drugs per beneficiary covered by the programs was $1157 (interquartile range, $247-$5609) compared with $367 (interquartile range, $100-$1500) for the noncovered drugs. Off-patent brand-name drugs (cost: >$10 000) were covered by a mean of 3.1 (SD, 2.0) patient assistance programs, whereas their generic equivalents were covered by a mean of 1.2 (SD, 1.0) patient assistance programs.Conclusions and Relevance: In 2018, among 274 patient assistance programs operated by the 6 independent charity foundations, the majority did not provide coverage for uninsured patients. Medications that were covered by the patient assistance programs were generally more expensive than those that were not covered. [ABSTRACT FROM AUTHOR]

Objectives. To examine whether the share of pharmaceutical industry funds allocated to patient advocacy organizations (PAOs) is disproportionately large in the United States relative to other industrialized countries and to compare pharmaceutical companies' disclosure practices across industrialized countries. Methods. We examined funding of PAOs among the 10 largest pharmaceutical companies in 2016. We compared funding allocated to organizations across 8 large industrialized countries and pharmaceutical companies' disclosure practices in each country. Results. Only 6 of the 10 largest pharmaceutical companies disclosed their financial transactions with PAOs in the United States. All 10 companies disclosed transactions in France, Germany, and the United Kingdom, with varying levels of disclosure in other countries. In 2016, the 6 companies that disclosed transactions in the United States allocated 74% of their patient advocacy funding ($88 million) in the United States. Conclusions. The disproportionate funding of US PAOs in the absence of any disclosure requirements suggests that the United States should consider adoption of regulatory actions to enhance the transparency of relationships between the pharmaceutical industry and PAOs, and to ensure the integrity of public health decision-making. [ABSTRACT FROM AUTHOR]

The prices patients pay for brand-name medications are rising faster than many other medical care costs. Some observers claim that the business practices of pharmaceutical benefit managers are partly responsible. How the process works is complicated, and this article explains what is happening. [ABSTRACT FROM AUTHOR]

Purpose Biosimilars can generate competition and provide cost savings over reference biologics for the Medicare program and beneficiaries. The extent to which these benefits can be realized in the Medicare Part D program depends on how biosimilars and biologics are placed in the formulary. We conducted a study to examine Medicare formulary placement of the first biologic to have 2 biosimilars on the market—infliximab and its biosimilars infliximab-dyyb and infliximab-abda. Methods All standalone and Medicare Advantage (MA) prescription drug plans (PDPs) offered in Medicare Part D were examined between September 2016 (ie, at the end of the last quarter before the launch of the first infliximab biosimilar) and September 2018, at which time a second biosimilar had been on the market for about 14 months. When PDPs covered both the reference biologic and a biosimilar, we compared the cost-sharing tier and the frequency of prior authorization and step therapy requirements for each drug. Results Nearly all PDPs covered infliximab throughout the study period. By September 2018, 31.7% of MA plans and 14.9% of standalone PDPs were covering a biosimilar on the market. Nearly all plans that covered a biosimilar also covered the reference product. Most plans (98% of standalone PDPs and 89% of MA plans) had placed prior authorization restrictions on both the biologic and the biosimilar. All plans covering both products placed them in the same cost-sharing tier. No plan required step therapy for either product. Conclusion Formulary placement of infliximab biologic and biosimilars in Medicare Part D is not optimized to generate cost savings for the Medicare program and beneficiaries, whose cost sharing is often based on the drug's list price. The Medicare program should provide incentives for PDPs to expand biosimilar coverage. [ABSTRACT FROM AUTHOR]