Breakthrough Clinical Results
ExCellThera announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending conditional marketing authorization for Zemcelpro® (UM171 Cell Therapy). Zemcelpro® is a novel cryopreserved haematopoietic stem cell transplantation product intended for adults with haematological malignancies requiring an allogeneic haematopoietic stem cell transplantation following myeloablative conditioning, who lack access to suitable donor cells. The European Commission is expected to make a final decision within two months. If approved, Zemcelpro® would be the first and only therapy of its kind in the EU. The positive opinion was based on a conditional Marketing Authorization Application (MAA), with additional filings planned for the US, Canada, UK, and Switzerland. Zemcelpro® has received orphan drug and regenerative medicine advanced therapy designations from the FDA, and orphan medicinal product, ATMP, and PRIME designations from the EMA.
Key Highlights
- Positive CHMP opinion recommends conditional marketing authorization for Zemcelpro® in the EU.
- Zemcelpro® is designed for adult blood cancer patients lacking suitable donor cells for stem cell transplantation.
- If approved, it will be the first therapy of its kind in the EU.
- Additional regulatory filings are planned in the US, Canada, UK, and Switzerland.
Incidence and Prevalence
Global Burden of Multiple Myeloma (MM)
Multiple myeloma (MM) poses a growing global public health challenge. Data from the 2021 Global Burden of Diseases (GBD) study reveals a concerning trend: from 1990 to 2021, the global prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with MM more than doubled, with a more pronounced increase observed in males. This escalating burden is evident across all Social-Demographic Index (SDI) regions, with middle SDI regions experiencing the most rapid growth. Projections based on ARIMA modeling suggest that this upward trend will persist over the next 15 years. Notably, the proportion of MM cases attributed to high body mass index (BMI) also saw a global increase, rising from 6.40% in 1990 to 7.96% in 2021. MM predominantly affects older adults, with the highest incidence and mortality rates observed in the 70-74 age group.
In 2022, an estimated 188,000 MM cases and 121,000 deaths occurred globally. Eastern Asia and Northern America each accounted for approximately one-fifth of all cases (21% and 19%, respectively), followed by South-Central Asia (11%) and Western Europe (9%). Incidence rates were consistently higher in men than in women across similar geographical patterns. Northern America and Australia/New Zealand exhibited the highest incidence rates (4/100,000 or higher for both sexes combined), while the highest mortality rates (1.8/100,000) were observed in Australia/New Zealand, Northern Europe, and Southern Africa. Projections suggest that, without intervention, MM incidence and mortality could increase by 71% and 79%, respectively, by 2045 compared to 2022 levels.
Global Burden of Hematologic Malignancies
Hematologic malignancies represent a significant portion of global cancer cases. Analysis of data from the Global Burden of Disease study (1990-2019) reveals a global increase in incident cases since 1990, reaching 1,343.85 thousand in 2019. However, the age-standardized death rate (ASDR) for all types of hematologic malignancies has been declining. In 2019, the ASDR for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were 4.26, 1.42, 3.19, and 0.34 per 100,000 population, respectively, with Hodgkin lymphoma showing the most substantial decline. The burden of these malignancies is generally higher in men, although this gender gap tends to decrease after peaking at a certain age. Regional variations exist, with Central Europe, Eastern Europe, East Asia, and the Caribbean showing the most significant increasing trends in the age-standardized incidence rate (ASIR) for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma, respectively. A rising proportion of deaths are attributed to high BMI, particularly in regions with high socio-demographic indices (SDI). Conversely, the burden of leukemia linked to occupational exposure to benzene and formaldehyde is more prevalent in low SDI areas.
Multiple Myeloma in the United States
In the United States, data from the Surveillance, Epidemiology, and End Results (SEER) 22 database (2000-2020) shows that most myeloma cases occurred in individuals aged 55 years or older (85.51%), men (54.82%), and non-Hispanic Whites (66.67%). Plasma cell myeloma was the most frequent subtype, with 193,530 cases recorded between 2000 and 2019. A significant decrease in the age-standardized incidence rate of myeloma was observed across all races/ethnicities, both sexes, and all age groups (AAPC: -8.02; 95% CI: -10.43 to -5.61) and particularly in those younger than 55 (AAPC: -8.64; 95% CI: -11.02 to -6.25) from 2019 to November 2020. Despite a general increase in myeloma incidence between 2000 and 2019, especially among younger Hispanic and non-Hispanic Black women, a notable decline in incidence rates was observed following the onset of the COVID-19 pandemic in 2020.
Unmet Needs and Targeted Populations in Hematological Malignancies (Based on PubMed Publications 2020-2023):
Hematological malignancies present diverse challenges, and research consistently highlights several unmet needs across various patient populations. Key themes and targeted populations include:
1. Supportive Care Needs:
- Psychosocial distress: Patients experience high levels of anxiety, depression, fear of recurrence, and uncertainty about the future. This is particularly evident during diagnosis, treatment, and post-treatment phases. Caregivers also experience significant distress and unmet needs related to patient care and support. Interventions targeting psychosocial support, information provision, and care coordination are needed.
- Information and Communication: Patients desire clear, accessible, and tailored information about their disease, treatment options, side effects, and available support services. Improved communication between healthcare providers and patients is crucial for shared decision-making and addressing patient concerns.
- Physical and Daily Living Needs: Fatigue, pain, sleep disturbances, and other physical symptoms significantly impact patients' quality of life. Practical challenges related to mobility, self-care, and daily activities also contribute to unmet needs. Interventions addressing symptom management, rehabilitation, and practical support are necessary.
- Financial Concerns: The financial burden of cancer treatment, including travel costs, lost income, and medication expenses, creates significant hardship for patients and families. Financial support and assistance with navigating healthcare systems are needed.
2. Targeted Populations:
- Adolescents and Young Adults (AYAs): This population faces unique challenges related to developmental stage, fertility concerns, and social support. Age-appropriate information, treatment facilities, and peer support are crucial.
- Rural Patients: Limited access to specialized care, travel burdens, and financial constraints contribute to unmet needs in rural populations. Telemedicine and increased financial assistance may help address these challenges.
- Long-Term Survivors: Survivors experience long-term physical and psychosocial effects of treatment, including fatigue, pain, fear of recurrence, and emotional distress. Ongoing monitoring and tailored interventions are needed to address these long-term needs.
- Patients with Specific Subtypes: Certain subtypes of hematological malignancies, such as triple-negative breast cancer, present unique treatment challenges and require targeted therapies. Research focusing on specific subtypes is crucial for improving outcomes.
- Patients with Refractory Disease: Patients who do not respond to standard treatments have limited options and face significant unmet needs. Clinical trials and research focusing on novel therapies are essential for this population.
- Caregivers: Family members and informal caregivers provide essential support to patients but often experience high levels of distress and unmet needs themselves. Interventions targeting caregiver support, education, and respite care are needed.
3. Research and Clinical Trial Design:
- Standardization of Clinical Trial Design: Variability in eligibility criteria, endpoints, and statistical analysis across clinical trials makes it difficult to compare results and interpret the treatment landscape. Standardization is needed to improve the quality and comparability of research.
- Focus on Real-World Evidence: Clinical trials often have strict inclusion criteria that limit generalizability to real-world practice. Research incorporating real-world data can provide valuable insights into the effectiveness and safety of treatments in diverse patient populations.
- Development of New Biomarkers and Targeted Therapies: Despite advances in treatment, many patients still experience relapse or refractory disease. Research focusing on new biomarkers and targeted therapies is crucial for improving outcomes and addressing unmet needs.
- Personalized Medicine: Tailoring treatment strategies to individual patient characteristics, including genetic profiles and disease subtypes, can improve outcomes and reduce adverse effects. Research focusing on personalized medicine is essential for advancing cancer care.
4. Access to Care and Resources:
- Financial Barriers: The high cost of cancer care can limit access to treatment and supportive services, particularly for low-income and uninsured patients. Financial assistance and policy changes are needed to improve affordability and access.
- Geographic Barriers: Limited access to specialized care in rural areas creates significant challenges for patients and families. Telemedicine and mobile health technologies can help bridge geographic gaps and improve access to care.
- Health System and Information Needs: Patients and caregivers often struggle to navigate complex healthcare systems and access reliable information. Improved care coordination, patient navigation services, and accessible information resources are needed.
Addressing these unmet needs requires a multi-faceted approach involving healthcare providers, researchers, policymakers, and patient advocacy groups. By working together, we can improve the lives of individuals affected by hematological malignancies and strive towards better outcomes for all.
Drug used in other indications
Zemcelpro® (UM171 Cell Therapy) is currently being investigated for its potential in treating heart failure in addition to hematological malignancies.
Ongoing Trials for Heart Failure:
While the provided texts focus heavily on UM171's use in expanding hematopoietic stem cells for transplantation in hematological malignancies, one source mentions ongoing trials exploring cell-based therapies for heart failure. Specifically, it highlights UM171 as a potential therapeutic agent in this context. The review discusses several cell types being investigated for heart failure, including mesenchymal stromal cells (MSCs) derived from bone marrow, umbilical cord, or adipose tissue. It also mentions new approaches such as repeated cell treatment and intravenous delivery. However, it does not specifically detail the intervention models being used with UM171 in heart failure trials.
Intervention Models (Hypothetical, based on general cell therapy approaches for HF):
Since specific intervention models for UM171 in heart failure are not provided, we can infer potential approaches based on common cell therapy strategies for this condition:
- Intravenous Infusion: This method involves delivering UM171-expanded cells directly into the bloodstream. The cells are expected to migrate to the damaged heart tissue and contribute to repair and regeneration.
- Intramyocardial Injection: This approach involves injecting UM171-expanded cells directly into the heart muscle during a surgical procedure. This allows for targeted delivery to the affected area.
- Epicardial Engraftment of Engineered Tissue Products: This involves applying engineered tissue constructs containing UM171-expanded cells onto the surface of the heart (epicardium). This approach aims to promote integration and regeneration of the damaged tissue.
- Personalized Patient Selection Based on Pharmacogenomics: This strategy involves tailoring the treatment to individual patients based on their genetic makeup. This could involve selecting patients most likely to benefit from UM171 therapy or optimizing the dosage based on individual genetic factors.
- Repeated Dosing: Given that some studies have shown efficacy signals with a single dose of cell therapy in heart failure, repeated dosing of UM171-expanded cells might further enhance therapeutic benefits.
It's important to note that these are hypothetical intervention models based on general cell therapy strategies for heart failure. The actual intervention models used in ongoing UM171 trials for heart failure may differ. Further research and clinical data are needed to determine the specific approaches being used and their efficacy.