Houston Methodist Leads Phase 2 Clinical Trial for Achilles Tendinopathy

Houston Methodist is one of only three clinical sites in the United States participating in a groundbreaking international Phase II trial evaluating an alternative approach to treating mid-portion Achilles tendinopathy using locally delivered microspheres.

The trial, sponsored by Novartis, potentially represents a significant advance in the orthopedic management of tendinopathy.

Rather than relying on systemic immunomodulatory medications or invasive surgical intervention, this investigational therapy aims to directly target local inflammation and tendon degeneration through a single ultrasound-guided peritendinous injection.

The therapeutic compound NGI226 is suspended within a biodegradable microsphere designed to release the active drug gradually over several weeks, providing sustained therapeutic effects at the site of injury.

“This is the first time in orthopedics that we are targeting a tendon disorder with a biologic agent delivered at the molecular level using controlled-release technology,” said Dr. Jason Ahuero, principal investigator for the trial at Houston Methodist and a specialist in foot and ankle orthopedic surgery. “It represents a paradigm shift in how we think about treating degenerative soft tissue conditions.”

An unmet need

Mid-substance Achilles tendinopathy is a painful disorder characterized by localized degeneration and inflammation of the Achilles tendon. The condition commonly arises from overuse, particularly in runners or athletes, but can also occur in less active individuals. Patients typically report progressive pain, stiffness, impaired range of motion and a palpable thickening of the tendon.

Conservative treatment modalities, including eccentric strengthening, physical therapy, orthotics and NSAIDs, form the cornerstone of early management.

However, a substantial portion of patients don’t receive meaningful relief from these treatments, prompting consideration of surgical debridement or tendon transfer. These procedures are associated with variable outcomes, prolonged recovery periods, and, in some cases, an increased risk of tendon rupture.

“Surgical outcomes for chronic mid-substance tendinopathy are inconsistent and can sometimes compromise tendon integrity,” Dr. Ahuero noted. “There is a clear unmet need for therapies that can address the biological basis of tendon degeneration without the morbidity of surgery.”

Trial design

The study is a randomized, double-blinded, placebo-controlled trial evaluating the local and systemic safety, tolerability and preliminary efficacy of NGI226 microspheres in patients with documented Achilles tendinopathy. The trial focuses on efficacy outcomes using a 3:1 randomization schema (active to placebo).

Participants receive a one-time peritendinous injection of either NGI226 or placebo under ultrasound guidance, followed by longitudinal monitoring for 24 weeks.

NGI226 microspheres are designed to release in a controlled fashion, modulating the inflammatory milieu surrounding the tendon while minimizing systemic exposure.

Inclusion criteria specify adults between the ages of 30 and 70 with imaging-confirmed mid-portion Achilles tendinopathy of two to 12 months duration who have failed a course of conservative therapy. Exclusion criteria include immunocompromised status, active malignancy and reproductive potential without contraceptive use, owing to the immunomodulatory nature of NGI226 and unknown reproductive risks.

“The delivery method in this population is one of the novel features,” Dr. Ahuero explained. “Local injection of a slow-release microsphere for the treatment of tendon disease has never been attempted in orthopedics.”

Outcomes monitoring

Throughout the six-month follow-up period, participants undergo serial assessments including pain scores, physical exams, range-of-motion testing and tendon function evaluations.

Advanced imaging — including ultrasound elastography and MRI — is used to track structural changes in the tendon. Biochemical monitoring via blood draws evaluates pharmacokinetics and screens for any systemic side effects.

“One of the primary endpoints is improvement in tendon compliance and elasticity, which we’re measuring through elastographic imaging,” explained Dr. Ahuero. “We are also monitoring functional improvements in mobility and exercise tolerance, which are critical patient-centered outcomes.”

Broader implications for tendon disease

The success of NGI226 in Achilles tendinopathy could open the door for similar biologic strategies in other common tendon disorders.

Houston Methodist’s participation in this trial reflects its broader mission to lead in translational and regenerative orthopedic research, Dr. Ahuero emphasized.

“There’s a real opportunity here to intervene before tendons fail completely,” Dr. Ahuero said. “Tendinopathy often precedes partial or full-thickness tears. If we can halt or reverse the degenerative cascade early, we may be able to avoid surgery altogether.”

The study is actively enrolling eligible participants through the end of summer 2025.