Non-traumatic femoral head necrosis (osteonecrosis) in adults is an acquired ischemic disease of the femoral head characterized by a multifactorial etiology. The initial manifestation is local, usually partial necrosis but the disease has the potential to progress to complete destruction of the femoral head with development of end-stage hip arthritis, and then requires joint replacement. Osteonecrosis of the femoral head seems to be most common in men between the ages of 30 and 50 years. Despite the low prevalence compared to primary osteoarthritis or degenerative arthritis, femoral head osteonecrosis has a significant economic impact because it largely affects individuals in the prime of life (peak age 35 years).
We have developed a small molecule, LLP2A-Ale that directs endogenous mesenchymal stem cells (MSCs), to the bone surface to form new bone. The MSCs are directed to the bone surface by LLP2A-Ale, and the MSCs are then able to simulate new blood vessel formation. It appears that LLP2A-Ale may have utility in a variety of conditions where new bone formation is required, including osteoporosis, fracture healing, glucocorticoid induced bone loss and osteonecrosis. Non-traumatic osteonecrosis has been selected as the first indication for LLP2A-Ale by CIRM because of the high unmet medical need, the absence of an effective treatment other than surgical joint replacement, and the clear need to attract and stimulate differentiation of mesenchymal stem cells into the region of necrotic bone. Our phase I study now initiated will evaluate the safety of LLP2A- Ale in patients on chronic glucocorticoid therapy, then our Phase 2 study will evaluate the safety and efficacy of LLP2A-Ale in patients with atraumatic osteonecrosis.
The goal of this project by the end of our phase 2 study is to increase bone homing of the endogenous MSCs with a small molecule (LLP2A-Ale) to form new bone as a novel treatment for atraumatic osteonecrosis with only 3-4 injections by mobilizing the endogenous MSCs to build bone. Our molecule would be highly competitive in this market as there is no currently approved treatment for atraumatic osteonecrosis and the risks would be in a very acceptable range.
All drug product development and non-clinical efficacy, toxicology and pharmacokinetic studies have been completed. IND 114011 was submitted to the FDA on 22 July 2016. An official Study May Proceed letter was received on 26 September 2016.
Currently, we have activated 3 clinical trial sites and started screening in the Phase 1a study on December 1, 2016. The 3 current sites include:
• Diablo Clinical Research in Walnut Creek, CA
• West Coast Clinical Trials in Costa Mesa, CA
• Metroplex Clinical Research in Dallas, Tx