Breakthrough Clinical Results
Hemogenyx Pharmaceuticals plc announced a protocol amendment to include pediatric patients with relapsed/refractory acute myeloid leukemia (R/R AML) in its Phase I clinical trial of HG-CT-1. HG-CT-1 is a CAR-T therapy currently being tested in adults with R/R AML. This amendment, submitted to the FDA, aims to expand access to the treatment for children and adolescents with this aggressive disease, addressing a significant unmet medical need. The company highlights the progress made in the adult cohort, with the first two patients already treated. The expansion reflects Hemogenyx's commitment to broadening the potential impact of HG-CT-1.
Key Highlights
- Amendment filed with the FDA to include pediatric patients with R/R AML in the Phase I trial of HG-CT-1.
- HG-CT-1 is a CAR-T therapy currently in clinical trials for adult R/R AML.
- Expansion aims to address the unmet medical need for effective treatments in pediatric R/R AML.
- First two adult patients in the trial have already been treated.
Incidence and Prevalence
Global Epidemiology of AML
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy impacting diverse populations globally. Estimating its precise global incidence and prevalence is challenging due to variations in data collection, diagnostic criteria, and reporting practices across countries. However, several studies utilizing large datasets like the Global Burden of Disease (GBD) provide valuable insights into the evolving epidemiology of AML.
Incidence:
- A 2022 study utilizing the GBD 2021 data estimated that the global incidence of AML has continued to rise, reaching 144,645 cases in 2021, up from 79,372 cases in 1990. This represents a substantial increase in the number of new AML diagnoses worldwide.
- Another study published in 2023 estimated the age-standardized incidence rates (ASRs) of AML in 27 countries, ranging from 0.70 to 3.23 cases per 100,000 persons. This study also projected crude incidence rate growth from 2024 to 2040, varying from +1% to +46% across the included countries.
- A 2017 study reported the age-adjusted incidence of AML in the United States as 4.3 per 100,000 annually. This study also highlighted the age-related risk of AML, with incidence increasing with age and a median age at diagnosis of 68 years in the US.
- A 2019 study reported 61,559 new cases of AML in the older age group (60-89 years). Over the past 30 years, the incidence rate in this age group increased by 1.67 per 100,000 people.
- A 2017 study reported a gradual increase in the global incidence of AML from 1990 to 2017.
- A 2023 study estimated that in adults, AML was the most common leukemia worldwide (males: 38%, ASR = 3.1; females: 43%, ASR = 2.4).
Prevalence:
- A 2017 study estimated the global prevalence of leukemia (all types) in 2017 at 2.43 million cases (95% uncertainty interval 2.19 to 2.59 million), with an age-standardized prevalence rate (ASPR) of 32.26 (95% UI 29.02 to 34.61). While this provides an overall picture of leukemia burden, it does not specifically isolate AML prevalence.
- A 2010 study estimated the prevalence of CML (not AML) to be approximately 70,000 in 2010, projecting an increase to 181,000 by 2050.
- A 2008 study estimated the prevalence of all myeloid malignancies (including AML) in the EU27 at 189,000 cases as of January 1, 2008.
Key Observations:
- AML incidence is increasing globally, particularly among older adults.
- There are significant regional variations in AML incidence and prevalence.
- High-income countries generally have higher AML incidence rates.
- AML remains a relatively rare malignancy compared to other cancer types.
- Data on global AML prevalence is limited, with most studies focusing on incidence or the broader category of leukemia.
Further research and standardized reporting are needed to improve the accuracy and comprehensiveness of global AML epidemiology data.
Economic Burden
Economic Burden of AML in the USA
- 2017-2020: Mean 1-year healthcare expenditures for Medicare Advantage beneficiaries were $81,818 (aged 75+) and $156,033 (aged 66-74).
- 2012-2018: Mean all-cause healthcare costs were $55,723 per-patient-per-month (PPPM) for active treatment and $68,596 PPPM for supportive care. Patients receiving active treatment with longer remission durations had lower PPPM costs ($71,823 for 0 to <3 months, $15,615 for 12+ months). However, total costs remained similar across remission durations due to varying follow-up times.
- 2008-2016: Mean total episode cost for relapsed/refractory (R/R) AML was $439,104, with $524,595 for patients with HSCT and $263,310 without HSCT. Inpatient visits ($308,978) and intensive care unit stays ($221,537) were the largest cost components.
- 2008-2016: Across various AML treatment episodes, R/R episodes had the highest mean cost ($439,104), followed by HSCT ($329,621), HIC-induction ($198,657), HIC-consolidation ($73,428), and LIC ($53,081). Hospitalization was the primary cost driver across all episodes.
- Premier Healthcare Database: Median total costs for intensive induction chemotherapy were $2904 (outpatient), $83,440 (inpatient), and $16,550 (ICU).
Economic Burden of AML in Europe
- 2017-2019 (Philippines): Mean healthcare expenditure for remission induction was $2504.78. Consolidation cost $3222.72 (3-4 cycles), relapsed/refractory disease cost an additional $3163.32 (relapsed) and $2914.72 (refractory), and palliative care cost $1687. Chemotherapy and therapeutics were the main cost drivers.
- 2024 (Various EU Countries): Mean per-patient direct costs varied by country and treatment phase. Induction chemotherapy ranged from 20,254 (Italy) to 92,378 (Spain). Consolidation ranged from 32,220 (Germany) to 42,137 (Netherlands). Transplantation ranged from 47,968 (Spain) to 192,628 (Sweden). Inpatient hospitalization and medication costs were the primary cost drivers.
- 2000-2012 (Netherlands): While the study focused on treatment patterns and survival, it highlighted the increased use of allogeneic stem cell transplantation, which is a significant cost driver in AML treatment.
Overall Trends and Considerations
- Rising Incidence: Studies indicate a steady increase in AML incidence in both the USA and Europe, contributing to the growing economic burden.
- Aging Population: AML predominantly affects older adults, and the aging population in both regions further exacerbates the economic impact.
- New Therapies: While novel therapies offer improved efficacy and safety, they are often more expensive than traditional chemotherapy, potentially increasing treatment costs.
- Hospitalization: Hospitalization, particularly ICU stays, remains a major cost driver in AML treatment across various settings and disease stages.
- Cost Variations: Costs vary significantly between countries and healthcare systems, reflecting differences in treatment practices, resource utilization, and unit costs.
- Indirect Costs: Many studies focus on direct medical costs, but indirect costs, such as lost productivity and informal caregiving, also contribute significantly to the overall economic burden.
Further research is needed to comprehensively assess the total economic burden of AML, including both direct and indirect costs, and to evaluate the cost-effectiveness of new therapies in different patient populations and healthcare settings.
Drug used in other indications
HG-CT-1, also known as glasdegib, is primarily indicated for use in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed acute myeloid leukemia (AML) in adult patients who are not candidates for intensive chemotherapy. While the provided text focuses heavily on AML, one source mentions that glasdegib was also evaluated in a clinical trial for patients with high-risk myelodysplastic syndrome (MDS).
Specifically, the phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) included patients with both AML and high-risk MDS who were unsuitable for intensive chemotherapy. In this trial, glasdegib was administered orally once daily in 28-day cycles, along with subcutaneous LDAC twice daily for 10 days of each cycle. The study compared the combination of glasdegib/LDAC to LDAC alone, with overall survival as the primary endpoint. The results showed a statistically significant improvement in overall survival with the combination compared to LDAC alone (8.8 months vs. 4.9 months, hazard ratio 0.51, p = 0.0004).
The provided texts do not mention any other indications for which HG-CT-1 is currently being trialed. It's important to note that clinical trial landscapes are constantly evolving, and new trials may have been initiated since the publication of these articles. Consulting updated clinical trial databases like ClinicalTrials.gov is recommended for the most current information on ongoing studies.