AT ACR 2017
SAN DIEGO (FRONTLINE MEDICAL NEWS) – Among patients with mild to moderate patellofemoral osteoarthritis, intra-articular administration of the novel agent TPX-100 was safe and associated with functional benefits up to 1 year, a proof-of-concept study showed.
“We don’t yet have a disease-modifying drug for osteoarthritis [OA]; that’s sort of the holy grail for researchers,” lead study author Dawn McGuire, MD , said in an interview at the annual meeting of the American College of Rheumatology. “All of the patient-reported outcome and patient function indices that we studied moved in the same direction, showing a benefit of TPX-100. I think this is very promising.”
In animal studies, TPX-100, a 23-amino acid peptide derived from Matrix Extracellular Phosphoglycoprotein (MEPE) that is being developed by Oakland, Calif.–based OrthoTrophix has been shown to induce articular cartilage proliferation and healing after experimental injury. In the first phase 2 study of its kind, Dr. McGuire, a neurologist who is chief medical officer and a cofounder of OrthoTrophix, and her associates at 15 sites randomized 118 patients with grade 1-3 bilateral patellofemoral OA confirmed by screening MRI to receive weekly injections of 200 mg TPX-100 or placebo (saline) in their contralateral knee at baseline, 7 days, 14 days, and 21 days. Patients underwent at least one MRI scan after baseline and completed the self-administered Knee Injury and Osteoarthritis Outcome Score (KOOS).
The study consisted of two parts. In Part A, four dose cohorts ranging from 20 mg to 200 mg per injection were enrolled. There were no dose-limiting toxicities or safety concerns at any dose, and the 200-mg dose was selected dose for Part B of the study.
The median age of the 118 patients was 60 years and their median body mass index was 29.2 kg/m2. No drug-related serious adverse events and no dose-limiting toxicities occurred across doses ranging from 20 mg to 200 mg per injection. The incidence of common adverse events such as knee pain was similar between placebo- and TPX-100-treated knees.
Quantitative MRI showed no measurable between-knee differences in cartilage thickness or volume at 6 or 12 months. However, statistically significant and clinically meaningful differences in knee function were observed in favor of TPX-100-treated knees, compared with controls, including KOOS activities of daily living (P = .008 at 6 and 12 months), KOOS knee-related quality of life (P = .21 at 6 months and P = .03 at 12 months), and a significant reduction in pain going up or down stairs (P = .004 at 12 months). Subjects’ use of nonsteroidal anti-inflammatory medications declined by 63% during the study.
“In this study, we see some terrific, long-term results in knee-related core activities, which certainly were disease modifying from the patients’ perspective,” said Dr. McGuire, who noted that a phase 3 study is being planned. “In addition, patient’s pain going up and down stairs improved significantly, with a marked reduction in analgesic use. Any of us who are experienced in these tough areas of medicine know that early results can look extremely promising, but we have to do larger confirmatory studies.”