New Knee Drug, TPX-100, Shows Signs of Cartilage Regeneration

Oakland, California-based OrthoTrophix, Inc. has reported 6- and 12-month clinical outcomes in mild to severe knee osteoarthritis (OA) patients treated with TPX-100. The results were announced at the 2018 Osteoarthritis Research Society International annual meeting in Liverpool, UK from April 26-29, 2018.

According to the company: “OrthoTrophix previously presented the results of a Phase 2 clinical study in which the company’s OA drug candidate, TPX-100 improved knee function and physical quality of life at 6 and 12 months after treatment compared with placebo (N=93).”

“A follow-on protocol, TPX-100-4, assessed the same patient reported outcomes in subjects who participated in TPX-100-1. The average time from the initial TPX-100 treatment was 30 months, with a range of 28 – 35 months. Exclusion criteria included knee surgery or investigational drugs for OA in the interim between TPX-100-1 and TPX-100-4. Of the 93 subjects in TPX-100-1, 53 enrolled in TPX-100-4.”

Chief Medical Officer Dawn McGuire, M.D. told OTW, “In light of very strong results in animal models of osteoarthritis with our lead compound, TPX-100, we realized that we had an opportunity to investigate cartilage regeneration in patients with knee osteoarthritis.”

“TPX-100 is a novel 23-amino-acid peptide derived from matrix extracellular phosphoglycoprotein (MEPE), a 525-amino-acid protein that occurs naturally in humans and is known to be involved in the regulation of hard tissue and phosphate metabolism. Because of its small size, TPX-100 is being manufactured by a chemical synthesis process.”

“This is the second greatest cause of disability over 50 years of age. There are currently no approved drug treatments that substantially improve knee function and sustain this improvement over time. Of course, the ultimate goal is to modify the disease of osteoarthritis, as real-life patients’ experience of the disease, such that the need for knee replacement is reduced or eliminated.”

“A key feature of our proof of concept study design was selecting subjects with bilateral osteoarthritis such that changes in one knee could be compared with those in the other knee (one treated with TPX-100 and the other with placebo). This reduced the effects of potential factors that complicate studies between subjects such as weight, degree of activity, and genetic contributions to the diseases.”

“Importantly, TPX-100 was safe and well tolerated across a ten-fold range of doses. The dose of TPX-100 that we selected resulted in statistically significant and clinically meaningful improvements in critical knee functions (ascending and descending stairs, getting in and out of the car, both light and heavy house work, and ten other functional activities).”

“We plan to confirm our results in a much larger between-subject study. Thus far, it appears that intra-articular injections of TPX-100 result in at least 1-year to 2.5-year sustained improvement in knee function as determined by patient reported outcomes including the KOOS (Knee injury and Osteoarthritis Outcome Score) and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), both of which are validated and commonly used in osteoarthritis trials.”