OrthoTrophix, Inc. has initiated a Phase 2b clinical trial evaluating TPX-100, its lead therapeutic candidate for knee osteoarthritis (OA), marking a significant step toward developing a treatment that could modify disease progression rather than merely alleviating symptoms.
The Foster City, California-based biopharmaceutical company announced on May 12, 2025, that the trial will enroll patients with mild to severe knee OA across multiple sites in the United States. The study represents a critical advancement in addressing a condition that affects millions of Americans and lacks disease-modifying therapies.
Targeting the Underlying Bone Pathology in Knee OA
TPX-100 is being developed as a potential disease-modifying osteoarthritis drug (DMOAD), a therapeutic class designed to slow or halt disease progression. Current standard treatments for knee OA primarily focus on symptom management through pain relievers, anti-inflammatory medications, and eventually joint replacement surgery for advanced cases.
What distinguishes TPX-100's approach is its focus on subchondral bone pathology. While knee OA has traditionally been viewed as primarily a cartilage disease, recent evidence suggests that pathological changes in the subchondral bone—the bone layer that supports the joint cartilage—occur earlier and serve as key predictors of symptom progression, disease advancement, and eventual joint replacement.
This insight comes from a natural history study involving over 9,000 knees, which helped reshape understanding of OA disease progression. The findings align with TPX-100's mechanism of action, which appears to target these early bone changes.
Promising Phase 2a Results
The decision to advance to Phase 2b follows encouraging results from a previous randomized, placebo-controlled Phase 2a trial. In that study, TPX-100 demonstrated a favorable safety profile while producing clinically meaningful and statistically significant improvements in knee function compared to placebo.
Post hoc MRI analyses from the Phase 2a study, published in Arthritis Research & Therapy in 2021, revealed that TPX-100 treatment significantly reduced pathological bone-shape changes compared to placebo. These structural improvements correlated with functional benefits, suggesting that TPX-100 may address both symptoms and underlying disease processes.
"We were encouraged that the data supported the relationship between functional improvement and reduced pathological bone shape change observed in TPX-100-treated knees in our earlier study," stated Dawn McGuire, M.D., FAAN, Chief Medical Officer of OrthoTrophix. "This Phase 2b trial is a critical step toward validating TPX-100 as a potential first-in-class DMOAD."
Phase 2b Trial Design
The newly launched Phase 2b trial, titled "A 53-Week Study Evaluating the Safety and Efficacy of Intra-Articular Injections of TPX-100 in Patients with Mild to Severe Tibiofemoral Osteoarthritis of the Knee," is designed to confirm both the symptomatic improvements and structural effects observed in the earlier trial.
The study will evaluate TPX-100 administered as intra-articular injections directly into the affected knee joint. This administration route allows for targeted delivery to the affected area while potentially minimizing systemic side effects.
Full study details are available on ClinicalTrials.gov under the identifier NCT06865079, including specific inclusion criteria, dosing regimens, and primary and secondary endpoints.
Addressing a Significant Unmet Need
Knee osteoarthritis represents a substantial burden on both individual patients and healthcare systems. The condition affects approximately 14 million Americans, with prevalence expected to rise due to aging populations and increasing obesity rates. Current treatments primarily focus on symptom management rather than addressing disease progression.
If successful, TPX-100 could represent a paradigm shift in OA treatment by offering a therapy that modifies the disease course rather than just managing symptoms. This approach could potentially delay or prevent the need for knee replacement surgery, which, while effective, carries risks and limitations, particularly for younger patients.
Company Background and Partnerships
OrthoTrophix, founded in 2011 by three co-founders, focuses on the development and commercialization of therapies for hard tissue repair and regeneration, with a primary interest in osteoarthritis treatment.
The company has established a strategic partnership with American Regent, Inc. for TPX-100 in the U.S. market, while retaining rights for the rest of the world. This partnership may provide important commercial infrastructure should TPX-100 advance to market approval.
Dr. McGuire expressed optimism about the potential impact of TPX-100: "We are optimistic that these results could pave the way for a breakthrough in the treatment of knee osteoarthritis."
As the Phase 2b trial progresses, the medical community will be watching closely to see if TPX-100 can fulfill its promise as a disease-modifying therapy for one of the most common and debilitating joint conditions worldwide.
