Evolving Concept of Value in Health Economics and Outcomes Research: Emerging Tools for Innovation and Access to Cell and Gene Therapies for Rare Diseases.

Objective: Recent scientific breakthroughs have propelled the development of disease-modifying and potentially curative cell and gene therapies (CGTs) for rare diseases, including those diseases previously considered untreatable. However, the unique characteristics of CGTs pose challenges for the traditional methods of therapy value determination, reimbursement, and outcome evaluation used by regulatory and assessment agencies for product approval and market access. Notably, CGTs are one-time or short-course treatments, often first-in-class (precluding direct comparisons with effective alternatives), and have health benefits that are largely realized over time.

Risdiplam utilization, adherence, and associated health care costs for patients with spinal muscular atrophy: a United States retrospective claims database analysis.

Background: Spinal muscular atrophy (SMA) is a genetic neuromuscular disease associated with progressive loss of motor function. Risdiplam, a daily oral therapy, was approved in the United States for the treatment of SMA. Risdiplam's effectiveness depends on patient adherence to the treatment regimen.

Treatment preferences in spinal muscular atrophy: A swing weighting study for caregivers of patients with SMA types 1 and 2.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by skeletal muscle weakness and atrophy. Patients with SMA types 1 and 2 develop severe disabilities conferring substantial patient and caregiver burden. Caregiver treatment characteristic preferences are useful for informing treatment choices and improving adherence.

A practical approach for adoption of a hub and spoke model for cell and gene therapies in low- and middle-income countries: framework and case studies.

In the rapidly evolving landscape of biotechnologies, cell and gene therapies are being developed and adopted at an unprecedented pace. However, their access and adoption remain limited, particularly in low- and middle-income countries (LMICs). This study aims to address this critical gap by exploring the potential of applying a hub and spoke model for cell and gene therapy delivery in LMICs.

Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey.

Introduction: Onasemnogene abeparvovec (OA) is the only gene replacement therapy currently approved for spinal muscular atrophy (SMA) treatment. We sought to assess real-world patient and caregiver outcomes after OA treatment for SMA.

Methods: Patients who received OA were identified from the 2021 Cure SMA Membership Survey.

Effects of laser acupuncture on anthropometric parameters and lipid profile in obese adolescents.

The purpose was to compare the effects of diet and exercise and laser interference and maneuver on anthropometric parameters and blood effects of object agents. The study was a randomized controlled longitudinal study. It included 45 adolescents from both sexes who were divided randomly into two groups: one group was treated with low calorie diet and exercise as group A and group B was treated with low calorie diet, exercise, and laser acupuncture.

Recommendations for economic evaluations of cell and gene therapies: a systematic literature review with critical appraisal.

Objective: No consensus exists on the ideal methodology to evaluate the economic impact and value of new, potentially curative gene therapies. We aimed to identify and describe published methodologic recommendations for the economic evaluation of gene therapies and assess whether these recommendations have been applied in published evaluations.

Methods: This study was conducted in three stages: a systematic literature review of methodologic recommendations for economic evaluation of gene therapies; an assessment of the appropriateness of recommendations; and a review to assess the degree to which the recommendations were applied in published evaluations.

Valuation of Treatments for Rare Diseases: A Systematic Literature Review of Societal Preference Studies.

Introduction: We sought to synthesize published empirical studies that elicited and characterized societal valuations of orphan drugs and the attributes that may drive different valuations for orphan drugs versus other treatments.

Methods: We conducted a systematic literature review (SLR) in MEDLINE and EMBASE databases up to November 2, 2020. Search terms covered societal preferences and attributes of orphan drugs (e.

Value-Based Pricing for Patent-Protected Medicines Over the Product Life Cycle: Pricing Anomalies in the "Age of Cures" and Their Implications for Dynamic Efficiency.

Objectives: Conventional cost-effectiveness analysis (CEA) for the value-based pricing of new medicines largely ignores the implications of limited market exclusivity (ie, patent-protection periods plus any exclusivity granted by regulators). This paper explores the implications of this methodological shortcoming, which produces several pricing anomalies with potentially unintended effects on research and development (R&D) incentives.

Methods: We illustrate these implications by comparing 4 stylized examples of increasing complexity, from short-term cures for acute conditions to long-term cures for rare, health-catastrophic conditions.

International reference pricing of pharmaceuticals in the United States: Implications for potentially curative treatments.

Recent federal drug price control proposals have included mechanisms to benchmark US prices to international prices. These international price referencing (IRP) proposals recommend that the US government develop an index based on prices paid by a group of higher-income countries and restrict US prices to a narrow range of the index. IRP is a policy tool used across the globe to control drug costs, particularly in markets in which health care resources are limited.

Systematic Literature Review of Clinical and Economic Evidence for Spinal Muscular Atrophy.

Introduction: The recent advent of disease-modifying therapies (DMTs) has dramatically changed the treatment landscape of spinal muscular atrophy (SMA), and the multifaceted impact of this advancement has not been assessed thoroughly in the growing body of literature. We sought to summarize the literature on the natural history of SMA and the impact of SMA DMTs, including health-related quality of life (HRQOL) and utilities, clinical efficacy and safety, and economic impact.

Methods: Systematic literature reviews were conducted following PRISMA guidelines with no inclusive dates.

Variation in market access decisions for cell and gene therapies across the United States, Canada, and Europe.

Transformative cell and gene therapies have now launched worldwide, and many potentially curative cell and gene therapies are in development, offering the prospect of significant health gains for patients. Access to these therapies depend on decisions made by health technology assessment (HTA) and payer organizations. We sought to describe the emerging cell and gene therapies market access landscape by analyzing 17 US commercial payer medical policies, and HTA reports from five European countries and Canada.

Nusinersen for Spinal Muscular Atrophy in the United States: Findings From a Retrospective Claims Database Analysis.

Introduction: Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disorder caused by deletion/mutation of the survival motor neuron 1 gene, characterized by progressive loss of motor neurons, resulting in increasing muscular weakness, deteriorating motor function, and, in its most severe form, death before 2 years. Nusinersen, an antisense oligonucleotide that increases expression of the functional SMN protein, was approved for SMA by US and European regulatory agencies in 2016 and 2017, respectively. The indicated regimen requires intrathecal injections every 4 months, following the first four injections during the loading phase.

Matching-adjusted indirect treatment comparison of onasemnogene abeparvovec and nusinersen for the treatment of symptomatic patients with spinal muscular atrophy type 1.

Objective: Onasemnogene abeparvovec, a one-time intravenous gene replacement therapy, and nusinersen, an antisense oligonucleotide that requires ongoing intrathecal administration, have been evaluated as treatments for spinal muscular atrophy (SMA) type 1 in separate Phase III trials, but no head-to-head comparison studies have been conducted. Onasemnogene abeparvovec was compared with nusinersen using a matching-adjusted indirect comparison (MAIC) to estimate the treatment effect of onasemnogene abeparvovec relative to nusinersen for the treatment of symptomatic patients with SMA type 1 for up to 24 months of follow-up.

Methods: In the absence of studies for both onasemnogene abeparvovec and nusinersen with a common comparator, a Bayesian naïve indirect treatment comparison (ITC) and MAIC between onasemnogene abeparvovec and nusinersen were conducted to compare efficacy and safety of onasemnogene abeparvovec with nusinersen.

Gene therapy may not be as expensive as people think: challenges in assessing the value of single and short-term therapies.

At an upfront price of $2.125 million, the one-time gene therapy onasemnogene abeparvovec for spinal muscular atrophy, a rare neuromuscular disorder that is usually fatal by 2 years of age if untreated, has been called the "most expensive drug ever." This flawed characterization raises important methodological and policy issues regarding valuation of high-cost treatments.

An updated cost-utility model for onasemnogene abeparvovec (Zolgensma®) in spinal muscular atrophy type 1 patients and comparison with evaluation by the Institute for Clinical and Effectiveness Review (ICER).

: Recent cost-utility analysis (CUA) models for onasemnogene abeparvovec (Zolgensma®, formerly AVXS-101) in spinal muscular atrophy type 1 (SMA1) differ on key assumptions and results. : To compare the manufacturer's proprietary CUA model to the model published by the Institute for Clinical and Economic Review (ICER), and to update the manufacturer's model with long-term follow-up data and some key ICER assumptions. : We updated a recent CUA evaluating value for money in cost per incremental Quality-adjusted Life Year (QALY) of onasemnogene abeparvovec versus nusinersen (Spinraza®) or best supportive care (BSC) in symptomatic SMA1 patients, and compared it to the ICER model.

Economic burden of spinal muscular atrophy: an analysis of claims data.

: Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease. : Characterize direct costs associated with SMA management. : Truven Health Analytics MarketScan claims data (2012-2016).

Health economic evaluation of gene replacement therapies: methodological issues and recommendations.

: To provide recommendations for addressing previously identified key challenges in health economic evaluations of Gene Replacement Therapies (GRTs), including: 1) the assessment of clinical effectiveness; 2) the valuation of health outcomes; 3) the time horizon and extrapolation of effects beyond trial duration; 4) the estimation of costs; 5) the selection of appropriate discount rates; 6) the incorporation of broader elements of value; and 7) affordability. : A literature review on economic evaluations of GRT was performed. Interviews were conducted with 8 European and US health economic experts with experience in evaluations of GRT.

RESTORE: A Prospective Multinational Registry of Patients with Genetically Confirmed Spinal Muscular Atrophy - Rationale and Study Design.

Background: Dramatic improvements in spinal muscular atrophy (SMA) treatment have changed the prognosis for patients with this disease, leading to important new questions. Gathering representative, real-world data about the long-term efficacy and safety of emerging SMA interventions is essential to document their impact on patients and caregivers.

Objectives: This registry will assess outcomes in patients with genetically confirmed SMA and provide information on the effectiveness and long-term safety of approved and emerging treatments.