Breakthrough Clinical Results
Klotho Neurosciences announced that the FDA granted Orphan Drug Designation to its KLTO-202 (s-KL-AAV.myo) for the treatment of Amyotrophic Lateral Sclerosis (ALS). This designation provides incentives like tax credits for clinical trials and seven years of market exclusivity. KLTO-202 is a novel secreted-Klotho (s-KL) promoter, gene, and delivery system aimed at addressing the neurologic insult causing motor neuron damage in ALS. The company has completed proof-of-concept studies in animal models and is initiating manufacturing before meetings with the FDA and EMA to plan further development. KLTO-202 is not yet approved for human use.
Key Highlights
- FDA grants Orphan Drug Designation to Klotho Neurosciences' KLTO-202 for ALS.
- KLTO-202 is a novel secreted-Klotho (s-KL) promoter, gene, and delivery system.
- Designation provides incentives for clinical trials and seven years of market exclusivity.
- Company is initiating manufacturing and planning meetings with FDA and EMA.
Incidence and Prevalence
Global Epidemiology of Amyotrophic Lateral Sclerosis (ALS)
Global Incidence and Prevalence
The overall crude worldwide ALS incidence is estimated at 1.59 (95% CI 1.39-1.81) per 100,000 person-years according to a comprehensive worldwide study that identified 124 studies (110 studies of incidence and 58 studies of prevalence). In Western countries, the incidence is slightly higher at 1.89 per 100,000 person years with a prevalence of 5.2 per 100,000. Another study suggests that the incidence of ALS ranges from 1.7 to 2.3 per 100,000 persons worldwide.
The worldwide prevalence of ALS is estimated at 4-6/100,000 population. A meta-analysis reported varying pooled prevalence rates (per 100,000 persons) across different regions: - 6.22 for Europe - 5.20 for North America - 3.41 for Latin America - 3.01 for Asian countries excluding Japan - 7.96 for Japan
Regional Variations in Incidence
Significant geographical variations exist in ALS incidence:
-
In Sicily, southern Italy, the crude annual incidence rate is 1.4/100,000 person years (95% CI 1.33-1.47), with higher rates in males (1.71/100,000) than females (1.11/100,000).
-
In New Hampshire, USA, the age-standardized incidence rate ranges from 1.3 to 2.2 per 100,000 population per year.
-
In Minnesota, USA, the crude incidence rate is 2.2 cases per 100,000 person-years, with standardized incidence rates for the 2013 U.S. and European standard population at 2.2 and 2.39 cases per 100,000 person-years, respectively.
-
In Buenos Aires, Argentina, the crude incidence density was 3.17 per 100,000 person-years (95% CI 2.24-4.48) and the age-adjusted incidence density was 2.23 per 100,000 person-years (95% CI 1.45-3.01) during 2003-2010.
-
In Nova Scotia, Canada, the annual ALS age-adjusted incidence was 2.13 per 100,000 (2003-2004).
-
In Newfoundland and Labrador, Canada, the crude mean annual incidence was 2.4 per 100,000 (2000-2004).
-
In Beijing, China, the average annual incidence is significantly lower at 0.38 cases/100,000 person-years.
-
In Ecuador, studies of hospital populations found a crude incidence of 0.2-0.6 per 100,000.
-
In the Province of Turin, Italy (1971-1980), the crude incidence rate was 0.67/100,000/year, with age and sex adjusted rate of 0.69 cases per 100,000 inhabitants.
Regional Variations in Prevalence
-
In Europe, the median prevalence is 5.40 per 100,000 population (IQR 4.06-7.89), corresponding to an estimated 39,863 (29,971-58,244) prevalent cases.
-
In Sicily, the prevalence rate is 6.0/100,000 (CI 5.97-6.03).
-
In the United States, prevalence estimates have increased over time:
-
3.9 cases per 100,000 persons during 2010-2011
-
4.3 per 100,000 population for October 19, 2010-December 31, 2011
-
4.7 cases per 100,000 for 2012
-
5.0 per 100,000 for 2013
-
In Cyprus, the prevalence of ALS was 7.9 cases/100,000 population at the beginning of 2015.
Demographic and Temporal Patterns
-
ALS incidence increases with age until the age of 70-79 years, with the Minnesota study showing peak incidence of 8.3 per 100,000 in this age group.
-
ALS is more common among men (with a male to female ratio of approximately 1.5 to 1 or 1.6 to 1), with the Minnesota study reporting incidence of 2.4 per 100,000 in males versus 1.5 per 100,000 in females.
-
The incidence of ALS is lower among African, Asian, and Hispanic ethnicities compared to Caucasians. Lower incidence rates were found among people of African origin living in western countries.
-
In Brazil, there was a predominance of ALS in Caucasians compared to the general population with an odds ratio (OR) of 2.92 (95% CI 2.78-3.07). The OR in blacks was 0.04 (95% CI: 0.03-0.04), in mestizos was 0.05 (0.04-0.07), and in Indians was 0.02 (0.01-0.04).
-
Since 1957, incidence has been significantly rising year by year, though this upward trend weakened after standardization.
-
The estimated number of 2020 ALS cases across 22 countries studied is 121,028 prevalent cases.
-
Comprehensive ALS epidemiological studies are still lacking in many parts of the world, especially in Africa.
-
Significant heterogeneity in reported prevalence was observed within and between countries/geographic regions.
-
Introduction of palliative therapies in ALS will likely increase prevalence rates dramatically in the future.
Economic Burden
Economic Burden of ALS in USA and Europe
United States Economic Burden
The annual total cost per patient in the USA was estimated at US$ 69,475 (standardized to 2015 US$). The national economic burden of ALS in the USA was estimated at US$ 279-472 million. Notably, costs associated with ALS were greater than that of other neurological diseases.
European Economic Burden
Germany
In Germany, the mean annual total cost of illness was 78,256€ per patient, with a lifetime cost per patient estimated at 246,184€. The prevalence-based total burden yearly was 519,776,352€ in Germany. Nearly half of the costs were attributable to informal care. A more recent study estimated total annual costs per patient with ALS at 83,060€. From a cost-utility perspective, ALS was estimated at 138,960€/QALY.
United Kingdom
In the UK, patients receiving current care accrue estimated lifetime costs of £68,047 (2021/22 prices). With a 50% reduction in progression rates, a new disease-modifying therapy versus current care would likely exceed £735,000 per QALY gained.
Denmark
The annual total cost per patient in Denmark was US$ 13,667 (standardized to 2015 US$). It's worth noting that direct and indirect costs varied significantly across countries.
Cost Drivers and Factors
Several factors influence the economic burden of ALS:
- Disease progression and loss of individual autonomy were the main predictors of high cost of illness
- With increase of clinical severity stage, costs rose and quality of life decreased
- The score of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale was identified as one major influencing factor on total costs
- Higher out-of-pocket costs were associated with an ALS Functional Rating Scale gross motor subscore of ≤ 6, limb-predominant symptoms, and > 4 h/week of personal support care
Caregiver Impact
The economic burden extends beyond direct medical costs:
- Informal care is a significant component of total costs
- Patient's loss of physical functions was positively related with caregiver burden, anxiety, and somatic expression of depression
- Caregiver burden, depression, and anxiety were positively related with each other
HTA Approvals
HTA Approvals for ALS Drugs in the UK, France, and Germany
Based on the available information, there is no data regarding HTA approvals from the UK, France, and Germany for Amyotrophic Lateral Sclerosis (ALS) drugs in the last three years.
Drug used in other indications
Based on the provided context, I cannot provide specific information about KLTO-202 (s-KL-AAV.myo) clinical trials for indications other than ALS, intervention models, protocols, dosing regimens, administration methods, or current phase status of non-ALS trials, as this information is not present in the given context.
The context provided does not contain any relevant information about KLTO-202 (s-KL-AAV.myo) clinical trials, either for ALS or other indications.