Breakthrough Clinical Results
Relief Therapeutics announced that its RLF-TD011, a hypochlorous acid solution for epidermolysis bullosa (EB), was not granted Qualified Infectious Disease Product (QIDP) designation by the FDA. However, the company maintains Orphan Drug and Rare Pediatric Disease designations for RLF-TD011. The FDA's decision does not affect the company's development strategy. A pre-IND meeting with the FDA was held to discuss the next steps for advancing RLF-TD011 into later-stage development. RLF-TD011 has shown promising results in an investigator-initiated trial (NCT05533866) for infection control and wound healing in EB patients.
Key Highlights
- FDA denied QIDP designation for RLF-TD011 for epidermolysis bullosa (EB)
- RLF-TD011 retains Orphan Drug and Rare Pediatric Disease designations
- Pre-IND meeting with FDA held to plan next steps for later-stage development
- Promising results in investigator-initiated trial (NCT05533866) for EB patients
Incidence and Prevalence
Global Incidence and Prevalence of Epidermolysis Bullosa (EB)
Determining precise global incidence and prevalence of EB is challenging due to its rarity, variations in diagnostic criteria, and underreporting in many regions. Studies often focus on specific countries or regions, making direct global comparisons difficult. Furthermore, estimates can vary depending on the methodology used, such as clinical registries versus genetic modeling.
Challenges in Global Estimation:
- Rarity: EB is a rare disease, making large-scale population studies difficult and expensive.
- Diagnostic Variability: Accurate diagnosis requires specialized testing (immunofluorescence mapping, electron microscopy, genetic analysis), which may not be readily available in all settings. This can lead to misdiagnosis or underdiagnosis, especially of milder forms.
- Subtype Variation: EB comprises several subtypes with varying severity and clinical presentations, further complicating data collection and analysis.
- Data Collection Limitations: Comprehensive EB registries exist in some countries (e.g., Netherlands, England/Wales), but data from many parts of the world are lacking.
Available Data and Regional Variations:
While a single, definitive global estimate is unavailable, several studies provide insights into regional incidence and prevalence:
- United States: A study using the National EB Registry (1986-2002) reported an incidence of approximately 19.6 per million live births and a prevalence of 11.07 per million population.
- Netherlands: Data from the Dutch EB Registry (1988-2018) indicated a higher incidence of 41.3 per million live births and a prevalence of 22.4 per million population. This higher rate may reflect better case ascertainment due to a well-organized registry.
- England and Wales: The NHS EB service reported a prevalence of 34.8 per million population and an incidence of 67.8 per million live births (2002-2021). This study also noted declining birth rates for severe EB types, possibly due to increased genetic counseling.
- Germany: A population-based study estimated an incidence of 45 per million live births and a prevalence of 54 per million population. The higher incidence of junctional EB in this study may be related to early molecular diagnostics.
Recessive Dystrophic EB (RDEB):
One study using genetic modeling estimated a much higher incidence of RDEB (a subtype of dystrophic EB) in the US at 95 per million live births, significantly higher than registry-based estimates. This highlights the potential for underdiagnosis of RDEB.
Conclusion:
Current data suggest that the incidence and prevalence of EB vary considerably across different regions, likely due to differences in data collection methods and access to diagnostic services. While registry-based studies provide valuable information, they may underestimate the true burden of disease. Genetic modeling approaches may offer a more accurate reflection of disease incidence, but further research is needed to validate these findings. Continued efforts to improve EB diagnosis and reporting worldwide are crucial for better understanding the global epidemiology of this rare disease.
Economic Burden
Economic Burden of Epidermolysis Bullosa (EB) in the USA and Europe
USA:
One study estimated the annual burden of disease-associated malnutrition (DAM) across eight diseases, including epidermolysis bullosa, to be $156.7 billion in the United States, or $508 per U.S. resident. Nearly 80% of this burden was derived from morbidity associated with DAM, around 16% from mortality, and the remainder from direct medical costs of treating DAM. The total burden was highest in COPD and depression, while the burden per malnourished individual was highest in colorectal cancer and coronary heart disease.
A more recent study from 2022 focused on the economic burden and health-related quality of life (HRQoL) of 62 EB patients in Spain. The average annual cost per patient was 31,352, with direct healthcare costs representing 17.2% of the total, direct non-healthcare costs (mainly informal care) 71.3%, and productivity losses 11.5%. Severe EB cases had slightly higher average costs (31,706) than non-severe cases (30,337).
Another study estimated the annual cost of child sexual abuse (CSA), which can manifest similarly to EB, at $9.3 billion in the US. This includes the lifetime cost per victim of fatal CSA ($1,128,334 for females, $1,482,933 for males) and nonfatal CSA ($282,734 for females, $74,691 for males).
Europe:
A 2018 study estimated the cost of periodontal disease, which can cause oral manifestations similar to some forms of EB, at $3.49 billion in the US and 2.52 billion in Europe. Indirect costs due to periodontal disease amounted to $150.57 billion in the US and 156.12 billion in Europe.
A 2012 study assessed the social/economic costs and HRQoL of EB patients in eight EU member states. Average annual costs varied from 9,509 to 49,233 (reference year 2012). Direct healthcare costs ranged from 419 to 10,688, direct non-healthcare costs from 7,449 to 37,451, and labor productivity losses from 0 to 7,259. The average annual cost per patient across all countries was 31,390 (18% direct health costs, 74.8% direct non-healthcare costs, and 7.2% indirect costs).
A 2021 study quantified the prevalence, incidence, and mortality of EB in England and Wales. By March 2021, 2,594 individuals were registered, yielding a prevalence of 34.8 per million (EBS: 17 per million, DEB: 10.7 per million, JEB: 1 per million, Kindler EB: 0.3 per million). The total incidence was 67.8 per million live births. Birth rates fell progressively over the 19-year study period for all EB types. Median survival for JEB-S increased to 12.7 months over the past 5 years.
A 2021 study estimated the economic burden of stroke across 32 European countries at 60 billion in 2017, with healthcare accounting for 27 billion (45%). Annual stroke-related care costs were 59 per citizen, ranging from 11 in Bulgaria to 140 in Finland. Productivity losses cost 12 billion, and informal care cost 16 billion.
It is important to note that the available data on the economic burden of EB specifically is limited, and studies often focus on broader disease categories or related conditions. Furthermore, variations in methodology and cost components included make direct comparisons challenging.
RLF-TD011, also known as Oleogel-S10, is primarily being investigated for its potential in treating Epidermolysis bullosa (EB). While the provided text focuses heavily on EB research, it also mentions Oleogel-S10's use in treating partial thickness wounds of different etiologies. Unfortunately, the specific other indications for which RLF-TD011 is being trialed are not explicitly listed in the provided text.
Regarding intervention models, the text mentions a Phase 2 trial assessing re-epithelialization of wounds in EB using Oleogel-S10 and a subsequent Phase 3, two-phase study (EASE) to determine its efficacy compared to a placebo. EASE includes a 90-day, double-blind, randomized, placebo-controlled phase followed by 24 months of open-label, single-arm follow-up. The primary endpoint of the trial is the proportion of patients with complete closure of the target wound within 45 ± 7 days of treatment. Additional endpoints include wound burden, patient-reported outcomes, and safety.
While the provided text details the intervention model for EB, it does not describe the specific intervention models used for other wound types. More information would be needed to fully answer this part of the question.