Validation of a novel, adjuvant implant for post-metastatic skeletal lesions

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Project Summary Bone growth is critical to a favorable prognosis in the 70% breast cancer patients that have skeletal metastases, or approximately 175,000 patients per year in the US. Lytic lesions, or voids in the bone, result from local bone destruction caused by tumor cell-directed, osteoclastic bone re-absorption and lead to pathologic fracture and increased patient morbidity. Surgical intervention is necessary to prevent initial fracture or other skeletal related events, and involves stabilizing the defect created by the tumor. Currently, failure rates with these interventions are 42% for patients who survive more than 1-year after fixation for pathological fracture. Because of the high failure rates and increased patient survival, lytic lesions are affecting a growing patient population and account for approximately $2 billion in US healthcare expenditure per year. Patients with breast cancer bone metastases (i.e. a skeletal related event) require surgical intervention that stabilizes the tumor-directed defect using intra-medullar nails, total joint prostheses and bone cement. However, hardware and bone cement don't promote bone formation. Growth factors have become a popular option to increase bone healing, however, these therapies, such as BMP2 (Infuse®) or PTH (Forteo®) have been given a black-box warning by the FDA for patients with active tumor or patients who have been treated for tumor. In particular, BMP2 has been associated with increased tumor risk in patients who are undergoing X- radiation therapy or possess nascent undetected tumor. In response to this unmet need, Fusologics, LLC, a New York-based startup company is commercializing Nalovent™, a novel surgical implant with demonstrated ability to treat lytic lesions by effectively growing bone and inhibiting local growth of cancer cells. Based on the discovery of a novel molecular pathway for bone growth, Nalovent induces osteogenesis via the local administration of an implant that contains the opioid antagonist, naloxone, embedded in a collagen delivery vehicle. If validated, Nalovent would empower clinicians with a much-needed solution to heal lytic lesions and fight residual tumor in order to deliver significantly improved outcomes to the large and growing population of breast cancer patients with skeletal metastases. This proposal consists of two aims: 1) optimization of the Nalovent osteogenic implant around local inhibition of tumor growth, and 2) validation of the Nalovent implant in relevant in vivo studies. If successful, this proposal will demonstrate commercial proof-of-concept for the Nalovent implant and establish the foundation for a Phase II proposal to support remaining preclinical development in preparation for human trials.