Efgartigimod and Ravulizumab for Treating Acetylcholine Receptor Auto-antibody-Positive (AChR-Ab+) Generalized Myasthenia Gravis: Indirect Treatment Comparison.

INTRODUCTION: Efgartigimod and ravulizumab, both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), have not been directly compared. This paper assessed comparative effects of efgartigimod vs. ravulizumab for treating adults with AChR-Ab+ gMG using indirect treatment comparison methods. METHODS: The matching-adjusted indirect comparison used data from two randomized trials of adult men and women. The ADAPT (efgartigimod vs. placebo; individual patient data available) population was reweighted to match the CHAMPION (ravulizumab vs. placebo; index study; aggregate data available) population. The relative effect of efgartigimod versus placebo was estimated in this reweighted population and compared with the observed ravulizumab versus placebo effect to estimate the efgartigimod versus ravulizumab effect. The outcomes were Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r) assessed as cumulative effect (area under the curve; AUC) over 26 weeks (primary) and change from baseline at 4 weeks and time of best response (week 4 for efgartigimod; week 26 for ravulizumab). RESULTS: For MG-QoL15r, efgartigimod had a statistically significant improvement compared with ravulizumab over 26 weeks [mean difference (95% confidence interval): - 52.6 (- 103.0, - 2.3)], at week 4 [- 4.0 (- 6.6, - 1.4)], and at time of best response [- 3.9 (- 6.5, - 1.3)]. Efgartigimod had a statistically significant improvement over ravulizumab in MG-ADL at week 4 [- 1.9 (- 3.3, - 0.5)] and at time of best response [- 1.4 (- 2.8, 0.0)] and in QMG at week 4 [- 3.2 (- 5.2, - 1.2)] and at time of best response [- 3.0 (- 5.0, - 1.0)]. For AUC over 26 weeks, improvements were not significantly different between efgartigimod and ravulizumab for MG-ADL [- 8.7 (- 36.1, 18.8)] and QMG [- 13.7 (- 50.3, 22.9)]. CONCLUSION: Efgartigimod may provide a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+ gMG. Efgartigimod showed faster improvements in MG-ADL and QMG than ravulizumab.

A latanoprost cationic emulsion (STN1013001) vs. other latanoprost formulations (Latanoprost) in open angle glaucoma/ocular hypertension and ocular surface disease: an Italian cost-utility analysis.

BACKGROUND: STN1013001 is an innovative latanoprost cationic emulsion for open-angle glaucoma/ocular hypertension (OAG/OHT) and ocular surface disease (OSD). METHODS AND FINDINGS: A 5-year, 7 health states, 1-year cycle early Markov model-supported cost-utility analysis (CUA) of STN1013001 vs. other latanoprost formulations (Latanoprost) followed the Italian National Health Service (INHS) perspective.One-way, probabilistic and scenario sensitivity analyses tested the uncertainty of the baseline results. Value of information analysis (VOIA) investigated the potential cost-effectiveness of collecting further evidence. RESULTS: Over 5 years, the Markov model-supported CUA predicts STN1013001 to be potentially highly cost-effective vs. Latanoprost (+€57.60 cost at €2020 values; +0.089 Quality-Adjusted Life Years).The Incremental Cost-Utility Ratio (€647.65) falls well below the lower limit of the acceptability range proposed for Italy (€25,000-€40,000).Sensitivity analyses confirmed the robustness of the baseline findings. VOIA highlighted that further information might only be cost-effective for OAG/OHT utilities and OSD-related disutility. CONCLUSION: STN1013001 is potentially highly cost-effective and strongly dominant vs. Latanoprost for OAG/OHT+OSD patients from the INHS perspective. These findings should be re-assessed using the data from the ongoing Phase III trial (NCT04133311) comparing the efficacy and safety of STN1013001 vs. Latanoprost and with future real-world CUAs upon the availability of STN1013001 on the Italian market.

Current and Future Treatment of Retinitis Pigmentosa.

Retinitis Pigmentosa (RP) is a group of inherited retinal dystrophies (IRDs) characterised by progressive vision loss. Patients with RP experience a significant impact on daily activities, social interactions, and employment, reducing their quality of life. Frequent delays in referrals and no standard treatment for most patients also contribute to the high unmet need for RP. This paper aims to describe the evolving therapeutic landscape for RP including the rationale for advanced therapy medicinal products (ATMPs). A review of available data was conducted in three stages: (1) a search of publicly available literature; (2) qualitative research with physicians treating RP patients in France, Germany, Italy, Spain, and the UK; and (3) a review of leading candidates in the RP pipeline. Globally, there are currently over 100 drugs in development for RP; 50% of which are ATMPs. Amongst the 15 cell and gene therapies in late-stage development, 5 leading candidates have been selected to profile based on the development stage, drug target and geography: gene therapies AGN-151597, GS-030 and VMCO-1 and human stem cell therapies jCell and ReN-003. Hereditary retinal diseases are suitable for treatment with cell and gene therapies due to the accessibility of the retina and its immune privilege and compartmentalisation. Therapeutic approaches that aim to rescue photoreceptors (eg gene therapies) require that non-functional target cells are still present, whereas other therapies (eg cell therapies) are not reliant on the presence of viable photoreceptors. Gene therapies may be attractive as their fundamental goal is to restore vision; however, cell therapies will likely have a broader application and do not rely on genetic testing, which can delay treatment. Ensuring effective therapeutic options for RP patients across disease stages requires the continued diversification and advancement of the development pipeline, and sustained efforts to promote early patient identification and timely diagnosis.

Retinitis Pigmentosa: Burden of Disease and Current Unmet Needs.

Retinitis Pigmentosa (RP), a group of inherited retinal dystrophies characterised by progressive vision loss, is the leading cause of visual disability and blindness in subjects less than 60 years old. Currently incurable, therapy is aimed at restricting degeneration of vision, treating complications, and helping patients to cope with the psychosocial impact of their disease. Hence, RP is associated with a high burden of disease. This paper describes the current therapeutic landscape for RP and the disease burden for patients, caregivers, and society. A review of available data was conducted in three stages: (1) a literature search of publicly available information on all domains of RP; (2) a systematic literature review using Medline, Embase, the Cochrane Library and grey literature (GlobalData) on epidemiology and cost of RP; and (3) qualitative research with senior physicians treating RP patients in the EU4 and the UK to validate research findings from secondary sources. RP severely impacts the daily lives of over a million people worldwide. Progressive vision loss significantly affects the ability to perform basic daily tasks, to maintain employment, and maintain independence. Consequently, most patients will experience reduced quality of life, with a greater emotional and psychological impact than other conditions related to vision loss such as diabetic retinopathy or age-related macular degeneration. RP is also associated with a high level of carer burden, arising from psychological and financial stress. The therapeutic landscape for RP is limited, with few treatment options and minimal guidance for the diagnosis, treatment, and care of patients. A curative intervention, voretigene neparvovec (Luxturna®), only exists for 1-6% of patients. Although disease management can be successful in developing coping strategies, most patients live with this chronic, progressive condition without interventions to change the disease course. Innovative new therapies can transform the therapeutic landscape, provided appropriate clinical guidance is forthcoming.

Cost-Utility Analysis of STN1013001, a Latanoprost Cationic Emulsion, versus Other Latanoprost Formulations (Latanoprost) in Open-Angle Glaucoma or Ocular Hypertension and Ocular Surface Disease in France.

Purpose: To investigate the cost utility of STN1013001, a latanoprost cationic emulsion, versus Latanoprost in patients with open-angle glaucoma or ocular hypertension (OAG/OHT) and concomitant ocular surface disease (OSD) in France. Methods: An early Markov model, including 7 health states and a 1-year cycle length, was developed to estimate the cost utility of STN1013001 versus Latanoprost from the French health system perspective over a 5-year time horizon. The model was populated with pooled data (treatment adherence, quality of life, disease progression, and resource utilization) collected, via a questionnaire, from a convenience sample of 5 French glaucoma specialists. Remaining data were retrieved from published sources. Half-cycle correction and 2.5% real social discount rate were applied to costs (in €2020), life years saved (LYS), and quality-adjusted life years (QALYs). The incremental cost-utility ratio (ICUR) was contrasted against the informal willingness-to-pay (WTP) range for incremental LYS or QALY gained (€30,000-€50,000) suggested for France. One-way and probabilistic sensitivity analyses tested the robustness of the baseline ICUR. Results: Over a 5-year time horizon, STN1013001 resulted in an incremental 0.35 QALYs gained at an incremental cost of €7.39 compared to Latanoprost, resulting in an ICUR of €21.26. This is well below the lower limit of the unofficial WTP range proposed for France. Sensitivity analyses confirmed the robustness of the baseline results. Conclusion: Once on the market, STN1013001 will provide the French health system with a cost-effective treatment versus Latanoprost for OAG/OHT + OSD patients. These results should be confirmed by future economic evaluations carried out alongside empirical trials.

Cost-Utility Analysis of a Latanoprost Cationic Emulsion (STN1013001) versus Other Latanoprost in the Treatment of Open-Angle Glaucoma or Ocular Hypertension and Concomitant Ocular Surface Disease in Germany.

PURPOSE: This study aimed to estimate the cost-utility and economic value of STN1013001, a latanoprost cationic emulsion vs other latanoprost formulations (henceforth latanoprost) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) and concomitant ocular surface disease (OSD) in Germany. METHODS: An early 5-year Markov model-supported cost-utility analysis was performed to estimate costs, quality-adjusted life years (QALYs) and life-years saved (LYS) for STN1013001 vs latanoprost from the German health system perspective. The model included seven mutually exclusive health states and adopted a 1-year cycle length. The model was populated with pooled data derived, by means of a questionnaire, from a convenience sample of five German glaucoma specialists. Remaining data were derived from published sources. Data provided by the ophthalmologists included annual treatment adherence probabilities, utility values and resource utilization. The half-cycle correction as well as a discount rate of 3.0% per year were applied to costs (expressed in €2020), life-year saved (LYS) and QALYs. The incremental cost-utility ratio (ICUR) was contrasted against the informal willingness-to-pay (WTP) threshold for incremental LYS saved or QALY gained (€30,000) proposed for Germany. One-way and probabilistic sensitivity analyses (OWSA; PSA) tested the robustness of the base case ICUR. RESULTS: Over the 5-year time horizon, STN1013001 strongly dominates latanoprost as it is less costly (€1003.65 vs €1145.37; -12.37%) and produces more QALYs (2.612 vs 2.365; +10.44%) per notional patient. Baseline findings were robust against all the variations included in OWSA. PSA shows that STN1013001 has a 100% probability of being cost-effective vs Latanoprost at each WTP threshold for incremental QALY gained. CONCLUSION: Once on the market, STN1013001 will provide a cost-effective and possibly strongly dominant therapy vs latanoprost for OAG/OHT+OSD patients from a German health system perspective. Future empirical research should confirm these findings.