Breakthrough Clinical Results
OS Therapies Inc. announced additional overall and event free survival data from its Phase 2b clinical trial of OST-HER2 in recurrent, fully resected, pulmonary metastatic osteosarcoma. The data highlights significant survival benefits in patients with lung-only metastatic events. The company is preparing to file a Biologics License Authorization (BLA) with the FDA under the Accelerated Approval Program and Marketing Authorization Applications (MAAs) with MHRA and EMA, utilizing their Conditional Approval pathway. OST-HER2 has received Rare Pediatric Disease Designation and Fast-Track and Orphan Drug designations.
Key Highlights
- OST-HER2 shows promising overall survival data in recurrent, fully resected, pulmonary metastatic osteosarcoma patients.
- Patients with lung-only first metastatic event showed significantly improved 2-year overall survival compared to natural history comparator.
- OS Therapies plans to file for regulatory approval with FDA, MHRA, and EMA.
- OST-HER2 has a favorable safety profile compared to chemotherapeutic agents.
Incidence and Prevalence
Latest Estimates of Osteosarcoma Incidence and Prevalence
Osteosarcoma is the most common primary bone malignancy, originating from primitive bone-forming mesenchymal cells. Recent epidemiological data provides important insights into its global distribution and impact.
Incidence Rates
The incidence rates for osteosarcoma across all races and both sexes are: - 4.0 (3.5-4.6) per million persons per year for ages 0-14 years - 5.0 (4.6-5.6) per million persons per year for ages 0-19 years
A more recent study from 2022 reported a lower incidence of 1.56 cases per 1,000,000 per year, which is below previously reported worldwide rates.
Demographic Variations
Racial differences in childhood and adolescent osteosarcoma show significant variation: - Blacks: 6.8 per million persons per year - Hispanics: 6.5 per million persons per year - Caucasians: 4.6 per million persons per year
Gender disparities are also evident: - Males: 5.4 per million persons per year - Females: 4.0 per million persons per year
Age Distribution
Osteosarcoma exhibits a bimodal age distribution: - First peak during adolescence (10-14 years), coinciding with pubertal growth spurt - Second peak in adults older than 65 years, often representing a second malignancy frequently related to Paget's disease - Approximately 25% of cases occur in adults between 20 and 59 years old
Anatomical Distribution
The most common sites of osteosarcoma occurrence are: - Femur: 42% (75% in distal femur) - Tibia: 19% (80% in proximal tibia) - Humerus: 10% (90% in proximal humerus) - Skull or jaw: 8% - Pelvis: 8%
Survival and Mortality
The overall 5-year survival rate for osteosarcoma is 68%, with no significant gender difference. Death rates have been declining by about 1.3% per year. However, adult osteosarcoma patients have worse outcomes than pediatric patients.
Among childhood cancers, osteosarcoma ranks eighth in general incidence (2.4%), after several other common pediatric malignancies. Cancer deaths due to bone and joint malignant neoplasms represent 8.9% of all childhood and adolescent cancer deaths.
These statistics highlight the continued importance of research into osteosarcoma prevention, early detection, and treatment strategies, particularly for high-risk populations.
Emerging End Points
Key Endpoints Emerging for Osteosarcoma
Recent publications have highlighted several critical endpoints for osteosarcoma research and treatment evaluation. Overall survival (OS) and progression-free survival (PFS) remain fundamental metrics, with deep learning approaches successfully stratifying patients to predict these outcomes (P = 2.4 × 10 for OS and P = 0.016 for PFS). The 5-year survival rate of approximately 60% for early-detected cases drops dramatically to less than 20% for patients with lung metastasis.
Necrosis ratio has emerged as a significant prognostic indicator, with patients showing ≥90% necrosis after chemotherapy demonstrating better outcomes. Deep learning models can now estimate this ratio with accuracy comparable to expert pathologists, providing an objective tool for treatment response assessment.
Several molecular biomarkers have gained prominence as endpoints. VEGFR2 and PD-L1 expression (positive in 64.5% and 35.5% of patients, respectively) negatively correlate with overall survival. Nine representative genes (ANK1, TGFBR3, TNFRSF21, HSPB8, ITGA7, RHD, AASS, GREM2, NFASC) have been identified for diagnostic models.
Recent research has identified IMPDH2 and FTL as particularly promising markers for stratifying patients into risk groups. Multivariate analysis confirmed IMPDH2 maintains independent prognostic value (P=0.025). Overall survival significantly correlates with expression of FTL, PHB, ATAD2, ACTN1, and RRM2, as well as lactate dehydrogenase serum levels.
A 2024 study identified three cuproptosis-related lncRNAs (ZNF37BP, AL353759.1, and AC005034.5) as prognostic biomarkers with excellent predictive power. The AUC curves for 1-year, 3-year, and 5-year survival probabilities were 0.76, 0.84, and 0.89, respectively.
Molecular classification has enhanced understanding with four subtypes (S-I ~ S-IV) identified. A 2024 study further refined this into three subtypes (S1, S2, S3), with S1 displaying high tumor purity, significant chemoresistance, and overexpression of KIF20A, correlating with poor prognosis.
For patients with metachronous metastatic relapse, multivariate analyses showed that tumor size, type of metastasis, and ALP level at diagnosis were independent factors for overall survival.
A 2021 study created a disease-free survival predictor model including ZNF720, REEP3, CNNM2, and CGREF1 using TARGET datasets to help understand cisplatin resistance.
The presence of circulating tumor DNA (ctDNA) at diagnosis and specific genomic alterations such as MYC amplification have been identified as biological features associated with poor outcomes.
Despite these advances in endpoints, clinical trials over the past two decades have shown that most treatments fail to induce objective responses, though some may sustain disease control. The lack of driver mutations as effective treatment targets and predictive biomarkers of treatment effectiveness remains a significant challenge in osteosarcoma management.