Objectives: To estimate, at the indication level, durable gene and cellular therapy new product launches in the United States through 2030, and the number of treated patients. Methods:A statistical analysis of clinical trials pipeline data and disease incidence and prevalence was conducted to estimate the impact of new cell and gene therapies. We used Citeline's ® Pharmaprojects ® database to estimate the rates and timing of new product launches, on the basis of the phase of development, duration in phase, and probability of progression. Disease incidence and prevalence data were combined with estimates of market adoption to project the size of reimbursed patient populations. Results:We project that about 350 000 patients will have been treated with 30 to 60 products by 2030. About half the launches are expected to be in B-cell (CD-19) lymphomas and leukemias.Conclusions: Cell and gene therapies promise durable clinical benefit from a single treatment course. High upfront reimbursement for these products means that the total costs could exceed what the healthcare system can manage. This creates a need for precision financing solutions and new reimbursement models that can ensure appropriate patient access to needed treatments, increase affordability for payers, and sustain private investment in innovation.

Sickle cell disease (SCD) is a group of inherited genetic conditions associated with lifelong complications and increased healthcare resource utilization. Standard treatment for SCD in the US varies based on stage of the disease and observed clinical severity. In this study, we aim to evaluate the potential cost-effectiveness of a durable cell or gene therapy cure for sickle cell disease from the US healthcare sector perspective. We developed a lifetime Markov model to evaluate the cost-effectiveness of a hypothetical single-administration durable treatment (DT) for SCD provided at birth, relative to standard of care (SOC). We informed model inputs including direct healthcare costs, health state utility weights, transition probabilities, and mortality rates using a retrospective database analysis of commercially insured individuals and the medical literature. Our primary outcome of interest was the incremental cost-effectiveness ratio (ICER) of DT versus SOC evaluated at a base case willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY). We tested the robustness of our base case findings through scenario, deterministic sensitivity (DSA), and probabilistic sensitivity analyses (PSA). In the base case analysis, treatment with DT was cost-effective with an ICER of $140,877/QALY relative to SOC for a hypothetical cohort involving 47% females. Both males (ICER of $135,574/QALY) and females (ICER of $146,511/QALY) were similarly cost-effective to treat. In univariate DSA the base case ICER was most sensitive to the costs of treating males, DT treatment cost, and the discount rate. In PSA, DT was cost-effective in 32.7%, 66.0%, and 92.6% of 10,000 simulations at WTP values of $100,000, $150,000, and $200,000 per QALY, respectively. A scenario analysis showed cost-effectiveness of DT is highly contingent on assumed lifetime durability of the cure. A hypothetical cell or gene therapy cure for SCD is likely to be cost-effective from the US healthcare sector perspective. Large upfront costs of a single administration cure are offset by significant downstream gains in health for patients treated early in life. We find cost-effectiveness outcomes do not vary substantially by gender; however, several model parameters including assumed durability and upfront cost of DT are likely to influence cost-effectiveness findings.

No abstract

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR-T) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR-T clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR-T industry may be a robust response to success and failure of competitor products.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder with significant healthcare resource utilization in the United States (US). The clinical management throughout the course of the disease is variable. Children born with SCD in the US receive routine comprehensive care that significantly reduces their morbidity and mortality. Upon transition to adulthood, there are marked increases in disease-related complications and morbidity. The extent to which disease management costs vary by age and overall lifetime cost of treatment are unknown. The aim of this study is to estimate the total direct healthcare cost among patients with SCD in the US across consecutive age ranges. Methods: We estimated direct costs of chronic management for SCD through a retrospective database analysis of Optum's de-identified Clinformatics® Data Mart Database (CDM) commercial insurance medical and pharmacy claims from January 1, 2007 to December 31, 2017. CDM provides information on 15 to 18 million annual insured lives and roughly 57 million unique lives over our study period (2007-2017). The population spans 50 states and is similar to the US distribution with respect to sex, age, and geography. We identified patients using ICD-9-CM (282.4x or 282.6x) and ICD-10-CM (D57.x sans D57.3x) diagnosis codes. Patients were required to have at least one inpatient (IP) claim or three or more outpatient (OP) claims (spaced at least 30 days apart) with a diagnosis of SCD and minimum of one year of continuous enrollment in both medical and prescription drug coverage. Each patient's index date was designated the date of their first SCD-related claim for patients with SCD, or their first date of eligibility for patients without SCD (controls). We matched patients with SCD to controls using 1:1 propensity score matching without replacement with a greedy nearest neighbor algorithm. Propensity scores were generated using probit regression on covariates gender, state, plan type, year of birth, and index year. Total direct costs of healthcare including IP, OP, professional (PF), ancillary (AN), and pharmacy (RX) services were calculated first year post-index (Y1), second year post-index (Y2), third year post-index (Y3), and overall (annualized) post-index. We calculated annualized costs by aggregating all costs after index and dividing by the remaining number of years the patient was eligible for coverage. Average incremental costs (AIC) are defined as the mean difference in costs between patients with SCD and respective controls. We report AIC by decade of age on the patient's index date, inflated to 2018 US dollars. All analyses were performed in SAS 9.4 (SAS Institute, Raleigh, NC) and Stata 16.0 (StataCorp, College Station, TX). This study was approved by the University of Southern California's University Park Institutional Review Board (UPIRB). Results: We identified 10,447 patients with SCD along with 10,447 unique matched controls from 2007 to 2017. Average total costs (sum of IP, OP, PF, AN, and RX costs) for patients with SCD were greater at all age categories, relative to controls. Annualized AIC, i.e. costs attributable to management of SCD, ranged from $18,859 (SD = 44,716) for ages 0-9 to $43,586 (SD = 109,735) for ages 20-29 (Table 1). First-year AIC were consistently greater than second and third-year AIC across all age groups (Figure 1). For patients with SCD, AIC were greatest for patients in the 20-29 years band across all specifications. Details on AIC of SCD management across all consecutive age ranges are available in Table 1. Conclusions: The cost of disease management for patients with SCD in the US is substantial. We observe a rise in SCD-specific costs from childhood to early adulthood. This may reflect the higher risk of disease-associated complications and mortality seen during this period. Additionally, AIC first year after initial SCD-related claim are consistently higher compared to AIC in years two and three. This finding may be attributable to an increased utilization of healthcare services from previously underinsured patients with SCD. Future work should involve simulating estimated lifetime total direct cost of healthcare attributable to management of SCD for patients in the US. Disclosures No relevant conflicts of interest to declare.