Cell Therapy Trial Fails Primary Endpoint in Treating Muscle Injury After Arthoplasty for Hip Fracture

Pluristem’s phase 3 trial (NCT03451916) of allogeneic PLX-PAD cells for the treatment of muscle injury following arthroplasty for hip fracture has failed to meet its primary endpoint of improvements in Short Physical Performance Battery (SPPB) test at week 26 compared to placebo, although other improvements were seen.

“We were pleased to learn that the data from this phase III study reinforced the data from the phase I/II study, with PLX-PAD demonstrating an increase in muscle strength,” Yaky Yanay, chief executive officer and president, Pluristem, said in a statement. “While we were disappointed that this significant benefit did not translate to an SPPB score improvement, Pluristem will seek further regulatory advice to find a way to bridge the gap between the clear impact on muscle strength and the functionality score. We believe that we have an important responsibility to make this treatment available for patients, and we will explore business opportunities and partnerships to advance the development of this product candidate.”

Investigators observed a significant increase in Hip Abduction Strength (HAS) at week 26 for patients treated with PLX-PAD (n = 120), in the injured leg (P = .047) and uninjured leg (P = .073) and at week 52 in the injured leg (P = .0022) and uninjured leg (P= .0046). These data confirm previous data in a phase 1/2 study that showed a statistically significant improvement in muscle strength and volume in treated patients who underwent total hip replacement surgery due to osteoarthritis. PLX-PAD was well-tolerated.

Specifically, treated patients experienced an increase of 3.2kg from week 6 to week 26 in HAS compared to 1.3kg in the placebo group (P = .047) and an increase of 5.01kg from week 6 to week 52 compared to 0.86kg (P = .0022) in their injured legs. They showed an increase of 2.3kg from week 6 to week 26 compared to 0.51kg in the placebo group (P = .073) and an increase of 3.3kg from week 6 to week 52 compared to a decrease of 0.7kg in the placebo group (P = .0046) in their uninjured leg.

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Investigators compared the absolute HAS between study groups at week 52 and found that treated patients showed a 2.6kg higher score than placebo in the injured leg (P = .0511) and a 2.2kg difference (P = .113) in the uninjured leg. A positive trend in a 6-minute walk test distances was also seen at week 52. Treated patients (N=36) were able to walk 296 meters versus 266 meters in placebo (N=45).

“I am very encouraged by these results. They confirm our phase I/II study results, now presented in an even older patient population with significantly more comorbidities, and I believe that this confirms that regenerative medicine is indeed effective in elderly people,” principal investigatorTobias Winkler, MD, PhD, professor, Center for Musculoskeletal Surgery, Charité Berlin, added to the statement. “We observed a significant increase in muscle strength, which we believe demonstrates PLX-PAD’s ability to trigger muscle regeneration and maintain it over time. As an orthopedic surgeon, I see this increase in muscle strength as meaningful clinical evidence that PLX-PAD can be potentially beneficial for sport-, surgery-, and traumatic muscle-related injuries.”

The multinational double-blind, placebo-controlled study enrolled 240 patients in the US, Europe, and Israel. PLX-PAD cells are designed to release factors in response to tissue damaged by muscle trauma, ischemia, or inflammation that harness the body’s repair mechanisms to support regeneration and differentiation. The cells also have immune-modulating capabilities. PLX-PAD is also being studied in an investigator-initiated phase 1/2 study conducted by Tel Aviv Sourasky Medical Center for the treatment of steroid-refractory chronic graft versus host disease.

REFERENCE

Pluristem reports topline results from its phase iii study of muscle regeneration following hip fracture surgery. News release. Pluristem. July 13, 2022. https://www.pluristem.com/wp-content/uploads/2022/07/Pluristem_Hip_Topline_results_FINAL_FOR_RELEASE_isa.pdf