Apatone® is an investigational new drug undergoing clinical trials in the US. Pain relief, together with biomarkers known to cause bone loss in patients with total knee replacements is being evaluated. Phase IIb clinical study of Apatone B is expected to be completed in 2012.
The drug targets inflamed cells and qualifying patients have now safely taken Apatone daily for more than five years. Phase I/II clinical study resulted in no reportable adverse events.
Joint diseases account for half of all chronic conditions in persons aged 65 and older. Osteoarthritis is 2nd only to cardiovascular disease in producing chronic disability. More than 21 million Americans suffer from osteoarthritis and joint replacement surgery has become an increasingly popular elective procedure. One million Total Joint Arthroplasties (TJA's) are performed annually in the US. During the next 20 years this is expected to increase four fold.
Through receptors on the cell surface Apatone targets the same cells that are illuminated by Positron Emission Tomography (PET). In this way the drug selectively targets and then treats inflamed cells. The current study is designed to examine Apatone's effect on specific inflammatory factors known to degrade bone, a critical part of joint disease, some cancers and other indications.
Apatone has been under preclinical and clinical study for over a decade. In mid-2007 the drug was granted Orphan drug status by the FDA's Office of Orphan Products for treatment of late stage urinary bladder cancer. The mechanism of action relies on inflammatory targeting and intercellular redox unique to non-vitamin moieties of combined vitamins C and K3. Apatone selectively targets inflamed cells and inhibits NF-KB, a nuclear factor kappa-light-chain-enhancer of activated B cells.
Further clinical studies as an adjuvant cancer treatment are planned. However, despite the clinical success of TJA, approximately 10% of these procedures fall victim to an inflammatory condition that frequently leads to premature implant failure. Particulate wear debris is a principal cause of aseptic loosening and premature failure. An underlying factor is the activation of NF-KB. A protein complex controlling transcription of DNA, it is found in almost all human cells. Involved in cellular responses to stress, NF-KB plays a key role in inflammation. Inflammatory irritation of adjacent tissue and of the bone to which the implant is attached, cause debilitating pain to return, and in some instances a costly second restorative surgery.
While literature has shown that antioxidant enzymes and vitamins can treat aberrant cells, at present, this same approach has not yet been introduced to orthopaedics. Oral administration of Apatone following fine metallic debris exposure from TJA is expected to diminish the inflammatory reaction, and may provide a new, safe and effective vitamin-based treatment for periprosthetic osteolysis.