Medicaid spending and utilization of gene and RNA therapies for rare inherited conditions.

Gene and RNA therapies are promising treatments for many rare diseases. Pediatric populations that could benefit from these drugs are overrepresented among state Medicaid programs. Using Medicaid State Drug Utilization Data, we examined Medicaid spending and utilization of rare disease gene and RNA therapies. Between 2017 and 2022, the number of available gene and RNA therapies increased from 3 to 13, yearly Medicaid spending increased from $148.3 million to $879.7 million, and the number of yearly treatments (a proxy for number of patients) increased from 327 to 1638. Nearly all spending was attributed to spinal muscular atrophy (SMA) and Duchenne muscular dystrophy drugs. States participating in Medicaid pooled purchasing initiatives had 39% higher treatments per 100 000 enrollees with no differences in spending. Compared to states without a carve-out, states that carved SMA drugs out of managed Medicaid contracts had higher utilization (54%). Spending among carve-out states varied according to managed care enrollment, being higher for those with <80% of enrollees in managed care as compared with those with ≥80% of enrollees in managed care. This suggests that multi-state purchasing initiatives and managed care carve-outs can help increase access to gene and RNA therapies among Medicaid beneficiaries, but it is unclear if these strategies are effective at managing spending.

Global Production of Active Pharmaceutical Ingredients for US Generic Drugs Experiencing Shortages.

This study evaluates the characteristics of generic active pharmaceutical ingredients (APIs) used to manufacture drugs with shortages in the US and facilities producing APIs worldwide.

Addressing the Drug-Shortage Crisis in Oncology.

This Viewpoint offers strategies for addressing shortages in essential chemotherapeutic drugs.

Ownership and Interoperability Challenges of Alzheimer Monoclonal Antibody Registries.

This Viewpoint addresses the challenges that the Centers for Medicare and Medicaid Services faces to collect real-world data on the effectiveness and safety of lecanemab from external registries to achieve its coverage with evidence development objectives.

Spending on Dual Over-the-Counter and Prescription Drugs in the Medicare Part D Program.

This study compares Medicare and patient spending for dual over-the-counter and prescription drugs with their over-the-counter cash prices.

Exploring the Influence of Health Insurance Plans on Biosimilar Adoption Rates.

BACKGROUND: We conducted a study to investigate the role of health insurance plans on biosimilar adoption among commercially insured patients in the USA. Flexible and rigid health plans may exhibit differing biosimilar coverage due to variations in cost considerations, formulary design, and provider networks. OBJECTIVE: To identify the characteristics of switchers and biosimilar initiators for six biologic-biosimilar pairs. METHODS: Using claims data from 2015 to 2019, we implement sequential regression models to assess the role of health plans on biosimilars adoption. FINDINGS: We found that low-flexibility plans, such as Health Maintenance Organization (HMOs) and Exclusive Provider Organization (EPOs), are more likely to have patients who are switchers and/or biosimilar initiators. CONCLUSION: Our findings highlight the importance of health insurance plan design in promoting biosimilar uptake.

Filgrastim and infliximab biosimilar uptake in Medicare Advantage compared with Traditional Medicare, 2016-2019.

BACKGROUND: Medicare Advantage (MA) and Traditional Medicare face different financing structures and incentives and may implement different strategies to encourage biosimilar uptake. Strategies used by health insurers can influence biosimilar uptake, which can in turn promote savings to insurers and patients. OBJECTIVE: To compare filgrastim and infliximab biosimilar uptake between MA and Traditional Medicare from 2016 to 2019 and examine biosimilar uptake by different MA carriers and plan types (Health Maintenance Organization [HMO] or Preferred Provider Organization). METHODS: We use a 2016-2019 nationally representative random 20% sample of the carrier (physician) and outpatient paid claims for Traditional Medicare data and final-action carrier and outpatient records for MA data. We compare quarterly biosimilar uptake from 2016 to 2019 for the first 2 drugs with biosimilar competition: (1) filgrastim, (Neupogen, originator), and biosimilars tbo-filgrastim (GRANIX) and filgrastim-sndz (ZARXIO), and (2) infliximab (Remicade, originator), and biosimilars infliximab-dyyb (Inflectra) and infliximab-abda (Renflexis). RESULTS: From their introduction, there was consistently greater uptake of filgrastim and infliximab biosimilars in MA compared with Traditional Medicare. By Q4 2019, filgrastim biosimilar uptake was 7.6 percentage points higher in MA (80.3%) than Traditional Medicare (72.7%). By Q4 2019, infliximab biosimilar uptake was 28.7% and 15.4% in MA and Traditional Medicare, respectively. Kaiser HMO plans were primarily responsible for the higher uptake of biosimilars in MA; in Q4 2019, filgrastim and infliximab biosimilar uptake was 98.8% and 78.8%, respectively. CONCLUSIONS: Our findings suggest that filgrastim and infliximab biosimilar uptake is greater in MA compared with Traditional Medicare, which is driven in part by particularly high uptake of biosimilars in MA Kaiser HMO plans. This highlights the need for future work to examine specific strategies and levers employed by MA Kaiser HMO plans and other insurers to increase biosimilar uptake, which can lead to cost savings for physician-administered drugs.

Role of Registries in Medicare Coverage of New Alzheimer Disease Drugs.

This Viewpoint discusses how the design of the Centers for Medicare & Medicaid Services (CMS) registry could impact Medicare's ability to evaluate whether monoclonal antibodies are reasonable and necessary for patients with Alzheimer disease and help physicians understand when the drug is most beneficial.

Incorporating Added Therapeutic Benefit and Domestic Reference Pricing Into Medicare Payment for Expensive Part B Drugs.

OBJECTIVES: Identify expensive Part B drugs and evidence for each drug's added benefit and model a reimbursement policy for Medicare that integrates added benefit assessment and domestic reference pricing. METHODS: A retrospective analysis using a 20% nationally representative sample of 2015 to 2019 traditional Medicare Part B claims. Expensive drugs were defined as having average annual spending per beneficiary exceeding the average annual social security benefit ($17 532 in 2019). For expensive drugs identified in 2019, added benefit assessments conducted by the French Haute Autorité de Santé were collected. For expensive drugs with a low added benefit rating, comparator drugs were identified in French Haute Autorité de Santé reports. For each comparator, average annual spending per beneficiary in Part B was computed. Potential savings from 2 reference pricing scenarios were calculated: reimbursing expensive Part B drugs with low added benefit at the level of each drug's (1) lowest cost comparator and (2) beneficiary-weighted-average cost of all comparators. RESULTS: The number of expensive Part B drugs grew from 56 in 2015 to 92 in 2019. Of the 92 expensive drugs in 2019, 34 offer low added benefit. Implementing reference pricing for these expensive drugs with low added benefit could have saved an estimated $2.1 billion if prices were set based on spending for their lowest cost comparator, or $1 billion if prices were set based on the weighted average of spending for comparators. CONCLUSION: Reference pricing based on added benefit assessment could be used to address the launch prices for expensive Part B drugs with low added benefit.

Estimating Changes in Medicare Part D and Commercial Insurer Insulin Spending Amid Planned State-Led Biosimilar Insulin Production in California.

This cross-sectional study evaluates the cost savings of state-led manufacturing and selling of biosimilar insulin.

Accelerated approval drug labels often lack information for clinical decision-making.

STUDY OBJECTIVE: We evaluated US Food and Drug Administration labels for drugs approved under the accelerated approval pathway and whether these labels contained in sufficient information regarding their accelerated approval. DESIGN: Retrospective, observational, cohort study. DATA SOURCE: Label information for drugs with an accelerated approved indication were ascertained from two online platforms: Drugs@FDA and FDA Drug Label Repository. INTERVENTION: Drugs with indications receiving accelerated approval after January 1, 1992, but had not received full approval by December 31, 2020. MEASUREMENTS: Outcomes include whether the drug label indicated the use of the accelerated approval pathway, identified the specific surrogate marker(s) that supported it, or described the clinical outcomes being evaluated in post-approval commitment trials. RESULTS: 253 clinical indications corresponding to 146 drugs received accelerated approval. We identified a total of 110 accelerated approval indications across 62 drugs that had not received full approval by December 31, 2020. A total of 13% of labels for accelerated approved indications lacked sufficient information that approval was via the accelerated approval or based on surrogate outcome measures: 7% did not mention accelerated approval but described surrogate markers, 4% did not mention accelerated approval nor describe surrogate markers, and 2% mentioned accelerated approval but did not describe surrogate markers. No label described the clinical outcomes being evaluated in post-approval commitment trials. CONCLUSION: Labels for accelerated approved clinical indications that do not yet have full approval should be revised to include the information required in the FDA guidance to help guide clinical decision-making.

Cancer Outcomes Among Prediabetes and Type 2 Diabetes Populations With Dietary and Physical Activity-based Lifestyle Interventions.

CONTEXT: People with type 2 diabetes (T2D) have higher risks of cancer incidence and death. OBJECTIVE: We aimed to evaluate the relationship between dietary and physical activity-based lifestyle intervention and cancer outcomes among prediabetes and T2D populations. METHODS: We searched for randomized controlled trials with at least 24 months of lifestyle interventions in prediabetes or T2D populations. Data were extracted by pairs of reviewers and discrepancies were resolved by consensus. Descriptive syntheses were performed, and the risk of bias was assessed. Relative risks (RRs) and 95% CIs were estimated using a pairwise meta-analysis with both a random-effects model and a general linear mixed model (GLMM). Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation framework, and trial sequential analysis (TSA) was conducted to assess if current information is enough for definitive conclusions. Subgroup analysis was performed by glycemic status. RESULTS: Six clinical trials were included. Among 12 841 participants, the combined RR for cancer mortality comparing lifestyle interventions with usual care was 0.94 (95% CI, 0.81-1.10 using GLMM and 0.82-1.09 using random-effects model). Most studies had a low risk of bias, and the certainty of evidence was moderate. TSA showed that the cumulative Z curve reached futility boundary while total number did not reach detection boundary. CONCLUSION: Based on the limited data available, dietary and physical activity-based lifestyle interventions had no superiority to usual care on reducing cancer risk in populations with prediabetes and T2D. Lifestyle interventions focused on cancer outcomes should be tested to better explore their effects.

Competition And Vulnerabilities In The Global Supply Chain For US Generic Active Pharmaceutical Ingredients.

The US supply of generic drugs is heavily dependent on the global supply chain for sources of generic active pharmaceutical ingredients (APIs) for the US pharmaceutical market. Data from Clarivate Analytics' Cortellis Generics Intelligence database were analyzed to perform a systematic examination of generic APIs produced globally for the US market during 2020-21. We identified a total of 565 facilities producing 1,379 unique generic APIs across forty-two countries. India, China, and Italy were the top producers; 14 percent of APIs were manufactured in the US. About a third of APIs were manufactured by a single facility, and another third were manufactured by two or three facilities. More than one in every five APIs reflected markets in which current Food and Drug Administration standards would have failed to detect low competition because there were three or fewer API manufacturers despite there being four or more manufacturers of finished generic drugs. Monitoring the API supply is crucial to identifying vulnerabilities in the US pharmaceutical supply chain and identifying drugs that could represent potential priorities for domestic production. Incentives in the US may be needed to support API production to safeguard against supply-chain disruptions.

Developing Prioritization Criteria to Identify Target Drugs for CalRx, the California Generic Drugs Initiative.

OBJECTIVES: This study aimed to establish criteria to identify priority drugs for CalRx, a California-sponsored initiative to support the manufacture and distribution of affordable generic drugs. METHODS: A web-based ranking exercise was implemented with key stakeholders in August 2020, using pricing, spending, and public health criteria identified through a review of academic literature and public health agency reports. A total of 39 of 40 invited stakeholders in 4 different categories-patient advocates, healthcare providers, health insurers, and health policy and economic experts-participated in this study (98% response rate). RESULTS: Drugs that treat large populations, drugs that represent high cost to payors, and drugs that represent high cost to consumers were ranked a priority, receiving > 10% of ranking weights. Drugs that treat conditions with high morbidity or mortality, drugs without therapeutic alternatives, and drugs treating vulnerable populations represented criteria of further interest (9%-10% of weights). Shortage risk and curative effect (8%-9% of the weights), high price increases, communicable disease treatments, and high unit prices (< 8% of the weights) represented the bottom of the priority distribution. CONCLUSIONS: This study suggests that drugs that treat large populations, drugs that represent large costs to payors, and drugs that represent large costs to consumers should be the priority for California's CalRx generic drug initiative. A prioritizing algorithm will assist California in determining top drugs to target from a public health and spending perspective as it plans the rollout of the CalRx initiative and negotiates with drug manufacturers.

Estimating Savings Opportunities From Therapeutic Substitutions of High-Cost Generic Medications.

Importance: Use of generics is generally understood as a cost-saving practice. However, pharmacy benefit managers have an incentive to place higher-priced generic drugs on insurers' drug formularies to profit by creating a large difference between the price negotiated with pharmacies and the price paid by insurers (what is known as spread pricing). Objective: To examine price differentials and savings potential between high-cost generics and corresponding therapeutic alternatives of same clinical value and lower cost. Design, Setting, and Participants: This cross-sectional analysis examined the top 1000 generics in Colorado's all-payer claims database (CO-APCD) in 2019. High-cost generics and lower-cost generic therapeutic alternatives of same clinical value constituted the study sample. Data were analyzed from January 2019 to December 2019. Exposures: Generic drug prices measured by transaction prices, average wholesale price (AWP), and national drug acquisition average cost (NADAC). Main Outcomes and Measures: Price differentials between the high-cost generics and the corresponding therapeutic alternatives. Levels of discounts and savings that could be achieved if the high-cost generics had been substituted by their therapeutic alternatives. Results: This cross-sectional study of the top 1000 CO-APCD generics identified 45 high-cost products that had lower-cost therapeutic alternatives of same clinical value. Overall, high-cost generics were 15.6 times more expensive than their therapeutic alternatives (median values). If the lower-cost alternatives had been used, total spending would have been reduced from $7.5 million to $873 711, resulting in 88.3% savings. Most substitutions (28 of 45 [62.2]%) involved different dosage forms or different strengths of the same drug and provided mean (SD) discounts of 94.9% (3.8%) and 77.1% (19.9%), respectively. Conclusions and Relevance: In this study, replacing high-cost generics with lower-cost alternatives of same clinical value would produce savings of nearly 90%. Plan sponsors should be aware that some generics are associated with higher spending and should periodically review the specific products driving their generic drug spending. Substitution of high-cost generics may provide a simple pathway to offer the same therapeutic benefit at lower cost to patients and insurers.