Paul Romness, CEO of OS Therapies, discusses the Plausible Mechanism Framework draft guidance and how it will affect the approval process of OST-HER2 LM for the treatment of osteosarcoma.
Osteosarcoma is the most common type of bone cancer, typically occurring in adolescence. Although osteosarcoma tends to occur in the larger bones, such as the shin, thigh, and upper arm, it can occur in any bone. A number of variants of osteosarcoma exist, including conventional types (osteoblastic, chondroblastic, and fibroblastic), telangiectatic, multifocal, parosteal, and periosteal. The exact cause of osteosarcoma is not known, however, at least one gene has been linked to increased risk.
The OST-HER2 LM vaccine is an immunotherapy that targets HER2-positive cancers such as osteosarcoma, breast, and esophageal cancer. It is designed to activate the immune system, triggering T cells to seek out and destroy cancer cells. The immunotherapy shows potential in preventing or eliminating recurrences of osteosarcoma, particularly through translational research and trials involving canines diagnosed with the disease. OST-HER2 LM is currently under review via the US Food and Drug Administration’s (FDA) Plausible Mechanism Framework.
The FDA’s Plausible Mechanism Framework
The US FDA’s Center for Biologics Evaluation and Research and Center for Drug Evaluation and Research recently issued the Plausible Mechanism Framework draft guidance. The guidance is designed for sponsors seeking approval for targeted individualized therapies by generating substantial evidence of effectiveness and safety when randomized controlled trials are not feasible due to small patient populations. The goal is to remove barriers and exercise regulatory flexibility to encourage scientific advances and the delivery of more cures and meaningful treatments for patients suffering from rare diseases.
The guidance focuses on therapies that target a specific genetic, cellular or molecular abnormality and are designed to address the underlying cause of disease. Key criteria include:
- Identifying the disease-causing abnormality.
- Demonstrating the therapy targets the root cause or proximate biological pathway.
- Relying on well-characterized natural history data in untreated patients.
- Confirming successful target drugging or editing.
- For traditional approval, therapies should demonstrate improvement in clinical outcomes, disease course, or biomarkers if they are established to predict clinical benefit.
For more information visit the Plausible Mechanism Framework guidance document.
OS Therapies has an upcoming Type B meeting with the FDA to discuss biomarker data and accelerated approval of OST-HER2 LM. Following that meeting, Mr. Romness noted that there are plans for a phase 3 global trial to start by September 2026. In addition to being involved in the Plausible Mechanism Framework, OST-HER2 LM has also received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations.
To learn more about osteosarcoma and other rare cancers, visit https://checkrare.com/diseases/cancers/