Clinical Benefit and Revenues of Drugs Affected by Rare Pediatric Disease Priority Review Vouchers, 2017-2023.

OBJECTIVE: To determine the clinical benefit of drugs that earned or redeemed rare pediatric disease priority review vouchers (PRVs) from 2017 through 2023, and the revenues generated by such drugs. STUDY DESIGN: In this cohort study, Federal Register documents, publicly available health technology agency (HTA) assessments, and financial filings were used to identify drugs that were issued or redeemed using a rare pediatric disease PRV from 2017 through 2023, and to assess their added therapeutic benefit and drug-specific global revenues. RESULTS: Among the 36 drugs whose approval resulted in issuance of a rare pediatric PRV, therapeutic benefit ratings were available for 17 (47%), with 9 (53%) rated as high by at least 1 organization. Mean annual global revenues were $363 million (year 1), $621 million (year 2), and $850 million (year 3). The median annual list price for drugs issued a voucher was $788,705. Vouchers were then redeemed for 15 different drugs; out of 13 drugs with therapeutic benefit ratings, 4 (31%) were high value. CONCLUSIONS: Drugs that treat rare pediatric diseases generate similar revenues compared with other brand drugs, and drugs with high therapeutic benefit tend to generate more revenue than those with low therapeutic benefit. Drugs that earned the rare pediatric disease PRV for their manufacturer generate significant revenues and the voucher may not be necessary to incentivize drug development in the rare pediatric disease space.

Availability and Cost of Expensive and Common Generic Prescription Drugs: A Cross-sectional Analysis of Direct-to-Consumer Pharmacies.

BACKGROUND: Direct-to-consumer (DTC) pharmacies sell generic prescription drugs, often at lower prices than traditional retail pharmacies; however, not all drugs are available, and prices vary. OBJECTIVE: To determine the availability and cost of generic drugs at DTC pharmacies. DESIGN: Cross-sectional study. SETTING: Five national DTC pharmacies in April and May 2023. PARTICIPANTS: Each qualifying form of 100 generic drugs with the highest cost-per-patient (expensive) and the 50 generic drugs with the highest number of patients (common) in Medicare Part D in 2020 MAIN MEASURES: Availability of these drugs and the lowest DTC pharmacy price for a standardized drug strength and supply (e.g., 30 pills), compared to GoodRx retail pharmacy prices. KEY RESULTS: Of the 118 expensive generic dosage forms, 94 (80%) were available at 1 or more DTC pharmacies; out of 52 common generic dosage forms, 51 (98%) were available (p < 0.001). Of the 88 expensive generics available in comparable quantities and strengths across pharmacies, 42 (47%) had the lowest cost at Amazon, 23 (26%) at Mark Cuban Cost Plus Drug Company, 13 (14%) at Health Warehouse, and 12 (13%) at Costco; for 51 common generic formulations, 16 (31%) had the lowest cost at Costco, 14 (27%) at Amazon, 10 (20%) at Walmart, 6 (12%) at Health Warehouse, and 5 (10%) at Mark Cuban Cost Plus Drug Company. For the 77 expensive generics with available GoodRx retail pharmacy prices, the median cost savings at DTC pharmacies were $231 (95% CI, $129-$792) or 76% (IQR, 53-91%); for 51 common generics, savings were $19 (95% CI, $10-$34) or 75% (IQR, 67-83%). CONCLUSIONS: Many of the most expensive generic drugs are unavailable at direct-to-consumer pharmacies. Meanwhile, less expensive, commonly used generics are widely available, but drug prices vary by pharmacy and savings are modest, requiring patients to shop around for the lowest cost.

Regulating Laboratory Tests: What Framework Would Best Support Safety and Validity?

Policy Points With increasing public attention to cases of inaccurate and misleading laboratory-developed tests, there have been calls for regulatory reform. To protect patients from faulty laboratory tests, we need a framework that balances comprehensive test review with laboratory flexibility. The Verifying Accurate Leading-edge IVCT [In Vitro Clinical Test] Development (VALID) Act would have helped ensure laboratory test safety and validity through a much-needed expansion of Food and Drug Administration (FDA) oversight. However, Congress did not pass the VALID Act in 2022, forcing the FDA to start the regulatory reform process on its own.

A Comparative Analysis of International Drug Price Negotiation Frameworks: An Interview Study of Key Stakeholders.

Policy Points Health care systems around the world rely on a range of methods to ensure the affordability of prescription drugs, including negotiating prices soon after drug approval and relying on formal clinical assessments that compare newly approved therapies with existing alternatives. The negotiation framework established under the Inflation Reduction Act is far more limited than other frameworks explored in this study. Adding elements from these frameworks could lead to more effective price negotiation in the United States. CONTEXT: In 2022, Congress passed the Inflation Reduction Act, which allowed Medicare, for the first time, to begin negotiating the prices for certain high-cost brand-name prescription drugs. Many other industrialized countries negotiate drug prices, and we sought to compare and contrast key features of the negotiation process across several health systems. We focused, in particular, on the criteria for selecting drugs for price negotiation, procedures for negotiation, factors that influence negotiated prices, and how prices are implemented. METHODS: We included four G7 countries in our analysis (Canada, France, Germany, and the United Kingdom [England]), two Benelux countries (Belgium and the Netherlands), and one Scandinavian country (Norway) with long-established frameworks for drug price negotiation. We also analyzed the Veterans Affairs Health System in the United States. For each system, we gathered relevant legislation, government publications, and guidelines to understand negotiation frameworks, and we reached out to key drug price negotiators in each system to conduct semistructured interviews. All interviews were recorded, transcribed, and coded, and data were analyzed based on an internal assessment tool that we developed. FINDINGS: All eight systems negotiate the prices of brand-name prescription drugs soon after approval and rely on formal clinical assessments that compare newly approved drugs with existing therapies. Systems in our study differed on characteristics such as whether the body performing clinical assessments is separate from the negotiating authority, how added health benefit is assessed, whether explicit willingness-to-pay thresholds are employed, and how specific approaches for priority disease areas are taken. CONCLUSIONS: High-income countries around the world adopt different approaches to conducting price negotiations on brand-name drugs but coalesce around a set of practices that will largely be absent from the current Medicare negotiation framework. US policymakers might consider adding some of these characteristics in the future to improve negotiation outcomes.

Sales Revenues for New Therapeutic Agents Approved by the United States Food and Drug Administration From 1995 to 2014.

OBJECTIVES: This study aimed to analyze worldwide sales of new therapeutic agents and to estimate the time it takes for product sales to exceed industry-wide average drug development costs. METHODS: Data obtained from company reports were analyzed to track worldwide sales of new medicines approved by the US Food and Drug Administration from 1995 to 2014. All sales figures were reported in 2019 US dollars. Kaplan-Meier curves were used to evaluate the time it took for discounted product sales to exceed the average costs associated with developing 1 new drug (accounting for the costs of failed trials), using published estimates of these costs. RESULTS: Based on data for 361 of 558 new therapeutic agents approved over the study period (median follow-up 13.2 years), mean sales revenue per product was $15.2 billion through the end of 2019; the median was $6.7 billion. These products jointly generated global sales of $5.5 trillion since approval. Revenues were highly skewed, with the 25 best selling products (7%, 25 of 361) accounting for 38% of this amount ($2.1 trillion of $5.5 trillion). Approximately 47% of products had discounted sales that exceeded the estimated industry-wide average costs of development within 5 years of approval, and 75% within 10 years. After attributing potential production, marketing, and other costs, these numbers dropped to 21% of products within 5 years of approval, and 46% within 10 years. CONCLUSIONS: Sales of new medicines approved from 1995 to 2014 were highly skewed, but many products had net discounted sales that exceeded the industry-wide average costs of development within 10 years of approval. An understanding of how sales revenues accrue in the years after initial approval, alongside data on business costs, can inform discussions about how to incentivize private investment in innovation while ensuring affordable prices for patients and the healthcare system.

Commercial markups on pediatric oncology drugs at 340B pediatric hospitals.

Eligible pediatric hospitals can purchase clinician-administered drugs at discounted rates through the 340B Drug Pricing Program and charge payers prices exceeding drug acquisition costs, but the magnitude of these markups is not known. In a study of newly approved oncology drugs at pediatric 340B hospitals, median negotiated prices ranged from 102% (interquartile range [IQR]: 91%-156%) of average sales price (ASP) at Phoenix Children's Hospital to 630% (IQR: 526%-630%) at Driscoll Children's Hospital. Pediatric hospitals participating in the federal 340B Drug Pricing Program can extract steep payments on new drugs from commercial insurers, though with wide variation between and within hospitals.

Use of Omalizumab for Pediatric Asthma After US Food and Drug Administration Expanded Indications.

PURPOSE: Research and regulatory approval for pediatric uses of prescription drugs often lag years after adult approvals, during which time substantial off-label use of medications in children can occur. We evaluated whether US Food and Drug Administration (FDA) regulatory actions affected the pediatric use of omalizumab, a biologic drug used to treat asthma. METHODS: In this serial cross-sectional study, we identified quarterly cohorts of children (0-18 years) with moderate-to-severe asthma within two large national claims databases of those with commercial insurance and Medicaid from 2003 to 2019. Using an interrupted time-series analysis, we fit segmented linear regression models to identify changes in the incidence of omalizumab use in 6-11-year-old children compared with 12-18-year-olds after two time points: (1) 2009Q3 when an FDA advisory committee voted against use for 6-11-year-old children and (2) 2016Q2 when FDA expanded omalizumab's labeling to include 6-11-year-old children. RESULTS: We identified 9298 new pediatric omalizumab users (84% Medicaid). Among 6-11-year-old children, the incidence of omalizumab use did not change following the FDA's initial review of evidence in 2009 and increased after 2016 Q2 FDA approval for this age group in both Medicaid (58 per 100 000 children with asthma, 95% confidence interval [CI] 27-89, p < 0.001) and commercial insurance (57 per 100 000, 95% CI 21-94, p = 0.003) compared with 12-18-year-old children. CONCLUSIONS: The use of omalizumab among asthmatic children aged 6-11 years remained steady after FDA advisory committee concerns in 2009 and increased after FDA expanded the indication to include this population in 2016. Additional market incentives may help to ensure the timely generation of evidence and regulatory approval of medications for children.

Moving Naloxone Over the Counter Is Necessary but Not Sufficient.

Naloxone is an opioid antagonist that is available in numerous formulations and can be easily administered to avert death from opioid overdose. Amid a historic overdose crisis in the United States, naloxone has a crucial role in stemming the loss of life. However, it remains largely inaccessible to the public. Recently, the U.S. Food and Drug Administration announced the approval of the first over-the-counter formulation of naloxone. Although this historic change provides an important opportunity to increase distribution of naloxone, we must take careful steps during this transition so that it does not paradoxically threaten overall access to this life-saving medication. Specifically, we must ensure that a larger supply of naloxone will meet the newly increased demand at a sustainable price for consumers who are most in need. We must also continue to prioritize comprehensive methods of distribution, such as overdose education and naloxone distribution programs, that serve as important tools to reach the most vulnerable populations. In addition, simultaneous investment in harm-reduction strategies, such as supervised consumption spaces, is critical to ensure that naloxone is available in settings where its life-saving potential can be most fully realized.

Comparative Effectiveness and Safety of Generic Versus Brand-Name Fluticasone-Salmeterol to Treat Chronic Obstructive Pulmonary Disease.

BACKGROUND: In 2019, the U.S. Food and Drug Administration (FDA) approved the first generic maintenance inhaler for asthma and chronic obstructive pulmonary disease (COPD). The inhaler, Wixela Inhub (fluticasone-salmeterol; Viatris), is a substitutable version of the dry powder inhaler Advair Diskus (fluticasone-salmeterol; GlaxoSmithKline). When approving complex generic products like inhalers, the FDA applies a special "weight-of-evidence" approach. In this case, manufacturers were required to perform a randomized controlled trial in patients with asthma but not COPD, although the product received approval for both indications. OBJECTIVE: To compare the effectiveness and safety of generic (Wixela Inhub) and brand-name (Advair Diskus) fluticasone-salmeterol among patients with COPD treated in routine care. DESIGN: A 1:1 propensity score-matched cohort study. SETTING: A large, longitudinal health care database. PATIENTS: Adults older than 40 years with a diagnosis of COPD. MEASUREMENTS: Incidence of first moderate or severe COPD exacerbation (effectiveness outcome) and incidence of first pneumonia hospitalization (safety outcome) in the 365 days after cohort entry. RESULTS: Among 45 369 patients (27 305 Advair Diskus users and 18 064 Wixela Inhub users), 10 012 matched pairs were identified for the primary analysis. Compared with Advair Diskus use, Wixela Inhub use was associated with a nearly identical incidence of first moderate or severe COPD exacerbation (hazard ratio [HR], 0.97 [95% CI, 0.90 to 1.04]) and first pneumonia hospitalization (HR, 0.99 [CI, 0.86 to 1.15]). LIMITATIONS: Follow-up times were short, reflecting real-world clinical practice. The possibility of residual confounding cannot be completely excluded. CONCLUSION: Use of generic and brand-name fluticasone-salmeterol was associated with similar outcomes among patients with COPD treated in routine practice. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence.

The U.S. Food and Drug Administration (FDA) approved eteplirsen (Exondys 51) for Duchenne muscular dystrophy in 2016 via its accelerated approval program on the basis of a study of 12 boys. After a contentious review process and a high-profile meeting of an external advisory committee, FDA leaders concluded that very small increases in treated patients' levels of dystrophin, a muscle protein, were reasonably likely to predict clinical benefit. The eteplirsen approval, which was followed by approvals of other drugs in the same class via the same pathway, has been controversial because of the questionable evidence underlying these decisions, delays in mandated postapproval testing, and high U.S. prices. Questions remain about the effectiveness and long-term safety of these products. Although the FDA initially set a November 2020 deadline for eteplirsen's manufacturer to complete a clinical trial determining whether the drug has clinical benefit, the company will not complete the trial until 2024 or later. The relationship between levels of truncated dystrophin, the muscle protein studied in eteplirsen's pivotal trial, and clinical outcomes remains uncertain. Despite recent legislative and regulatory changes to the FDA's accelerated approval pathway, the history of eteplirsen and similar drugs points to the need for additional reforms to better balance evidence generation with patient safety and access to promising medications. Lawmakers and regulators should take further action to limit excessive spending on unproven therapies and ensure that drug sponsors conduct robust and timely confirmatory trials after receiving accelerated approval.

Changes in Induced Medical and Procedural Abortion Rates in a Commercially Insured Population, 2018 to 2022 : An Interrupted Time-Series Analysis.

BACKGROUND: During the COVID-19 pandemic, access to in-person care was limited, and regulations requiring in-person dispensing of mifepristone for medical abortions were relaxed. The effect of the pandemic and accompanying regulatory changes on abortion use is unknown. OBJECTIVE: To estimate changes in the incidence rate of induced medical and procedural abortions. DESIGN: Serial cross-sectional study with interrupted time-series analyses. SETTING: Commercially insured persons in the United States. PARTICIPANTS: Reproductive-aged women. INTERVENTION: Onset of the COVID-19 pandemic in March 2020 and subsequent regulatory changes affecting the in-person dispensing requirement for mifepristone. MEASUREMENTS: Monthly age-adjusted incidence rates of medical and procedural abortions were measured among women aged 15 to 44 years from January 2018 to June 2022. Medical abortions were classified as in-person or telehealth. Linear segmented time-series regression was used to calculate changes in abortion rates after March 2020. RESULTS: In January 2018, the estimated age-adjusted monthly incidence rate of abortions was 151 per million women (95% CI, 142 to 161 per million women), with equal rates of medical and procedural abortions. After March 2020, there was an immediate 14% decrease in the monthly incidence rate of abortions (21 per million women [CI, 7 to 35 per million women]; P = 0.004), driven by a 31% decline in procedural abortions (22 per million women [CI, 16 to 28 per million women]; P < 0.001). Fewer than 4% of medical abortions each month were administered via telehealth. LIMITATION: Only abortions reimbursed by commercial insurance were measured. CONCLUSION: The incidence rate of procedural abortions declined during the COVID-19 pandemic, and this lower rate persisted after other elective procedures rebounded to prepandemic rates. Despite removal of the in-person dispensing requirement for mifepristone, the use of telehealth for insurance-covered medical abortions remained rare. Amid increasing state restrictions, commercial insurers have the opportunity to increase access to abortion care, particularly via telehealth. PRIMARY FUNDING SOURCE: Health Resources and Services Administration.

Regulatory Review Duration and Differences in Submission Times of Drugs in the United States and Europe, 2011 to 2020.

The speed of drug regulatory agencies in the United States and Europe is often a source of discussion. The objective of this research was to assess regulatory review duration of first and supplementary indications approved between 2011 and 2020 in the United States and Europe (European Union [EU] and Switzerland) and differences in submission times between the United States and Europe. Descriptive statistics were applied to review times between the jurisdictions and across the therapeutic areas. A regression analysis was done to estimate the association between approval agency and review times. The primary analysis cohort included 241 drugs approved in the United States, the EU, and Switzerland. Of these, 128 drugs had supplemental indications (331 in total) in the United States and 87 had supplemental indications (206 in total) in the EU. Overall median review duration from submission to approval subtracting the clock stop period was 39 weeks in the United States, 44 weeks in the EU, and 44 weeks in Switzerland. When review times within each drug were compared, the European Medicines Agency took a median of 3.7 weeks (IQR, -6.7 to 14.9 weeks) longer than the U.S. Food and Drug Administration and Swissmedic a median of 0.3 weeks (IQR, -10.6 to 15.3 weeks) longer. Median total review duration for supplemental indications was 26 weeks in the United States and 40 weeks in the EU. Applications were submitted a median of 1.3 and 17.9 weeks later in the EU and Switzerland, respectively, than in the United States. The regression analysis showed small differences in submission times between the United States and the EU (-2.1 weeks [95% CI, -11.7 to 7.6 weeks]) and larger differences between the United States and Switzerland (33.0 weeks [CI, 23.1 to 42.8 weeks]). It would be beneficial for patients if differences in submission times between the United States and Europe continue to be minimized.

Strategies to Help Patients Navigate High Prescription Drug Costs.

Importance: In the US, many patients struggle to afford prescription drugs, leading to adverse health outcomes. To improve cost-related medication nonadherence, prescribers and clinical staff must understand how to assist patients in overcoming high prescription drug costs. Observations: We reviewed the benefits and limitations of 7 strategies to help patients afford prescription drugs: co-payment cards, patient assistance programs, pharmacy coupons, direct-to-consumer pharmacies, public assistance programs, international online pharmacies, and real-time prescription benefit tools. We created an algorithm to help clinicians identify appropriate strategies based on a patient's health insurance and the type of drug (brand-name vs generic). For example, co-payment cards can lower out-of-pocket costs for privately insured patients taking brand-name prescription drugs. For uninsured individuals or those with public insurance like Medicare Part D who meet financial eligibility criteria, patient assistance or public assistance programs may be available. All patients, regardless of health insurance, can forgo insurance and purchase drugs directly using pharmacy coupons or direct-to-consumer pharmacies, which sometimes offer lower prices for generic drugs compared to insurance. For insured patients, such purchases do not count toward insurance deductibles or annual out-of-pocket maximums. Online international pharmacies provide a last resort for patients in need of brand-name drugs who lack affordable domestic options. Increasingly, prescribers can use real-time prescription drug benefit tools to estimate patient out-of-pocket costs and identify alternative lower-cost treatments for insured patients, but these tools can be inaccurate or incomplete. Conclusions and Relevance: The current patchwork of strategies to help patients manage high prescription drug costs highlights the structural and policy challenges within the US prescription drug market that impede affordable access for some patients. While these strategies provide tangible solutions for clinicians to help patients access medically appropriate but costly medications, they do not address the root causes of high drug prices.

Clinical Benefit and Regulatory Outcomes of Cancer Drugs Receiving Accelerated Approval.

Importance: The US Food and Drug Administration's (FDA) accelerated approval pathway allows approval of investigational drugs treating unmet medical needs based on changes to surrogate measures considered "reasonably likely" to predict clinical benefit. Postapproval clinical trials are then required to confirm whether these drugs offer clinical benefit. Objective: To determine whether cancer drugs granted accelerated approval ultimately demonstrate clinical benefit and to evaluate the basis of conversion to regular approval. Design, Setting, and Participants: In this cohort study, publicly available FDA data were used to identify cancer drugs granted accelerated approval from 2013 to 2023. Main Outcomes and Measures: Demonstrated improvement in quality of life or overall survival in accelerated approvals with more than 5 years of follow-up, as well as confirmatory trial end points and time to conversion for drug-indication pairs converted to regular approval. Results: A total of 129 cancer drug-indication pairs were granted accelerated approval from 2013 to 2023. Among 46 indications with more than 5 years of follow-up (approved 2013-2017), approximately two-thirds (29, 63%) were converted to regular approval, 10 (22%) were withdrawn, and 7 (15%) remained ongoing after a median of 6.3 years. Fewer than half (20/46, 43%) demonstrated a clinical benefit in confirmatory trials. Time to withdrawal decreased from 9.9 years to 3.6 years, and time to regular approval increased from 1.6 years to 3.6 years. Among 48 drug-indication pairs converted to regular approval, 19 (40%) were converted based on overall survival, 21 (44%) on progression-free survival, 5 (10%) on response rate plus duration of response, 2 (4%) on response rate, and 1 (2%) despite a negative confirmatory trial. Comparing accelerated and regular approval indications, 18 of 48 (38%) were unchanged, while 30 of 48 (63%) had different indications (eg, earlier line of therapy). Conclusions and Relevance: Most cancer drugs granted accelerated approval did not demonstrate benefit in overall survival or quality of life within 5 years of accelerated approval. Patients should be clearly informed about the cancer drugs that use the accelerated approval pathway and do not end up showing benefits in patient-centered clinical outcomes.

Federal Trade Commission Actions on Prescription Drugs, 2000-2022.

Importance: The Federal Trade Commission's (FTC) oversight role in the pharmaceutical market is critical to the health of patients and the health care system. This study characterized the FTC's policy on the pharmaceutical market in recent decades, identifying the types of actions it has favored, barriers it has faced, and authorities that remain untested. Objective: To review FTC legal actions in the pharmaceutical market from 2000-2022. Evidence Review: Legal actions were determined through manual review of search results from the FTC's online Legal Library as well as a 2023 FTC report on pharmaceutical actions. The alleged misconduct, type of legal action taken, timing, and outcome were collected from press releases, complaints, orders, and other legal documents. Findings: From 2000-2022, the FTC challenged 62 mergers, brought 22 enforcement actions against allegedly unlawful business practices, and made 1 rule related to pharmaceuticals. Alleged misconduct in enforcement actions involved anticompetitive settlements in patent litigation (n = 11), unilateral actions by brand manufacturers to delay generic competition (n = 6), noncompete agreements (n = 4), and monopolization (n = 3), with 10 outcomes involving monetary payment, totaling $1.6 billion. Of the 62 mergers the FTC challenged, 61 were allowed to continue, 58 after divesting certain drugs to third-party competitors. The FTC's reliance on drug divestitures decreased from 18 drugs per year from 2000-2017 to 4.3 per year from 2017-2023. Conclusions and Relevance: The FTC brought about 1 enforcement action and 3 merger actions per year against pharmaceutical manufacturers from 2000-2022, pursuing a small fraction of the estimated misconduct and consolidation in the pharmaceutical marketplace. Although the FTC faces substantial legal and practical limitations, important tools remain untested, including a rule defining "unfair methods of competition," that may allow it to more effectively prevent repetitive patterns of anticompetitive behavior.

Federal Enforcement of Pharmaceutical Fraud under the False Claims Act, 2006-2022.

CONTEXT: The False Claims Act is the US federal government's primary tool for identifying and penalizing pharmaceutical fraud. The Department of Justice uses the False Claims Act to bring civil cases against drug manufacturers that allegedly obtain improper payment from federal programs. METHODS: The authors searched the Department of Justice website for press releases published between 2006 and 2022 that announced fraud actions brought against drug companies. They then used the World Health Organization's Anatomical Therapeutic Classification index to identify the classes of prescription drugs implicated in fraud actions. FINDINGS: During fiscal years 2006-2022, payments by six manufacturers amounted to more than 28% of total payments made as a result of federal False Claims Act actions. Nervous system and cardiovascular drugs were the classes of medications most commonly implicated in alleged fraud. Federal officials most frequently alleged that companies improperly promoted nervous system drugs and paid kickbacks to increase revenues from cardiovascular, antineoplastic and immunomodulating, and alimentary tract and metabolism drugs. CONCLUSIONS: Despite frequent pharmaceutical fraud settlements and penalties, incidence of alleged fraud among drug companies remains high. Alternative methods for preventing and deterring fraud could help safeguard our health systems and promote public health, and policy makers should ensure that effective fraud enforcement complements preventive public health regulation.

Approval and therapeutic value of gene therapies in the US and Europe.

Gene therapies are a fast-growing area of innovation and hold promise for the treatment of many diseases currently with unmet medical need. To better understand the clinical importance of the current landscape of approved gene therapies, we conducted a systematic analysis of the approved gene therapies and their added therapeutic value. Through December 2022, 13 gene therapies have been approved in the US, 15 in the EU, and 9 in Switzerland. Nine gene therapies have been approved in all three jurisdictions, and 11 in both the US and EU. Among the 11 gene therapies approved in more than one jurisdiction, there were differences in the approved indications among the regulatory agencies, mostly the European drug agencies (EMA and Swissmedic) being more restrictive. Among the gene therapies with available therapeutic ratings, approximately two-thirds had high added therapeutic value, which is substantially higher than the average prevalence of high added therapeutic value ratings among new drugs and biologics (approximately one-third). However, therapies with high added therapeutic value will not be useful for patients if excessive prices limit access to them. Drug pricing reforms should address gene therapies to ensure access to new gene therapies that can offer important therapeutic value to patients.

Medicaid Spending on Antiretrovirals From 2007 Through 2019.

BACKGROUND: Antiretroviral (ARV) medications to treat human immunodeficiency virus (HIV) are a major contributor to Medicaid prescription drug spending. Despite having been used for over 3 decades, the first generic ARVs only recently became available, and many newer versions continue to be sold at high prices despite within-class competition. We estimated Medicaid spending on ARVs from 2007 through 2019. METHODS: Using public Medicaid State Drug Utilization data, we identified trends in ARV spending and use from 2007 through 2019. We estimated net spending and average prices (spending per 30-day supply), accounting for statutory Medicaid rebates, including a 15%-23% base rebate plus additional rebates if a drug's price increased faster than inflation. RESULTS: Among 48 ARVs, estimated net Medicaid spending from 2007 through 2019 was $25 billion for 17 million 30-day supplies. Annual use increased 118%, from 0.7 million 30-day supplies in 2007 to 1.6 million in 2019. During this time, estimated annual net spending increased 178%, from $1.1 billion to $3.0 billion, and average net prices increased 28%, from $1432 to $1830 per 30-day supply. CONCLUSIONS: Annual Medicaid net spending on ARVs nearly tripled from 2007 to 2019, due to a combination of expanded use and rising prices. Medicaid did not extract expected benefits from its mandatory inflationary rebates because they were offset by use of newer, more expensive ARVs. To better control spending related to products with incremental innovation, the US government should be authorized to assure that launch prices for new drugs are aligned with the added benefit they offer over existing therapies.

Analysis of risk evaluation and mitigation strategies for teratogenic drugs: Variation in primary and secondary prevention measures.

In an analysis of risk evaluation and mitigation strategies for teratogenic drugs, Ameet Sarpatwari, Beatrice Brown and Aaron Kesselheim explore the variation in primary and secondary prevention measures.

Patents and regulatory exclusivities on FDA-approved insulin products: A longitudinal database study, 1986-2019.

BACKGROUND: Insulin is the primary treatment for type 1 and some type 2 diabetes but remains costly in the United States, even though it was discovered more than a century ago. High prices can lead to nonadherence and are often sustained by patents and regulatory exclusivities that limit competition on brand-name products. We sought to examine how manufacturers have used patents and regulatory exclusivities on insulin products approved from 1986 to 2019 to extend periods of market exclusivity. METHODS AND FINDINGS: We used the publicly available Food and Drug Administration (FDA) Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) to identify all approved biosynthetic insulin products. Individual products approved under the same New Drug Application (NDA)-e.g., a vial and pen-were considered as separate products for the purposes of analysis. We recorded all patents and regulatory exclusivities listed in the Orange Book on each product and used Google Patents to extract the timing of patent application and whether patents were obtained on delivery devices or others aspects of the product. The primary outcome was the duration of expected protection, which was determined by subtracting the FDA approval date for each product from its last-to-expire patent or regulatory exclusivity (whichever occurred later). We performed a secondary analysis that considered overall protection on insulin lines-defined as groups of products approved under the same NDA with the same active ingredients manufactured by the same company. We also examined competition from follow-on insulin products-defined as products approved with the same active ingredients as originators but manufactured by different companies (approved via a specific drug approval pathway under section 505(b)(2) of the Food, Drug, and Cosmetic Act). During the study period, the FDA approved 56 individual products across 25 different insulin lines and 5 follow-ons across 3 different insulin lines. Thirty-three (59%) of the 56 products were drug-device combinations. Manufacturers of 9 products approved during the study period obtained patents filed after FDA approval that extended their duration of expected protection (by a median of 6 years). Approximately 63% of all patents on drug-device combinations approved during the study period were related to delivery devices. The median duration of expected protection on insulin products was 16.0 years, and the median protection on insulin lines was 17.6 years. An important limitation of our analysis is that manufacturers may continue to add patents on existing insulin products while competitors may challenge patents; therefore, periods of protection may change over time. CONCLUSIONS: Among several strategies that insulin manufacturers have employed to extend periods of market exclusivity on brand-name insulin products are filing patents after FDA approval and obtaining a large number of patents on delivery devices. Policy reforms are needed to promote timely competition in the pharmaceutical market and ensure that patients have access to low-cost drugs.