Phase III study of allogeneic PLX-PAD cells confirms “regenerative medicine is effective in elderly”.
Pluristem Therapeutics, a biotech designing cell therapy products that stimulate the body’s own regenerative mechanisms, has announced topline results from its multinational double-blind, placebo-controlled phase III study.
Pluristem designed the study to determine the efficacy, safety and tolerability of intramuscular administration of allogeneic PLX-PAD cells for the treatment of muscle injury following arthroplasty for hip fracture. The study enrolled 240 patients in the US, Europe and Israel.
Longevity.Technology: Age-related muscle loss starts early – after you hit 30, you begin to lose as much as 3% to 5% every ten years. Having less muscle mass not only makes you weaker, but leads to less mobility, and both contribute to increasing the risk of frailty, fractures and falls.
Pluristem’s placental cell-based therapies show potentially ground-breaking applications for treating damaged muscle, as well as haematology deficiencies, and inflammation. While being developed to respond to muscle trauma, the regenerative capacity could be harnessed in treatments for sarcopenia and frailty in the future.
PLX-PAD cells exhibit regenerative potential due to their capacity to release factors in response to distress signals from tissues that have been damaged by muscle trauma, ischemia or inflammation. These factors harness the body’s repair mechanisms to support tissue regeneration and differentiation. PLX-PAD cells also exhibit immune-modulating capabilities, playing a central role in the body’s response to tissue injury. This study is particularly interesting in that it shows older tissue can be triggered to regenerate.
PLX-PAD was demonstrated to be an effective accelerator of muscle strength and regeneration. A significant increase in Hip Abduction Strength (HAS) was observed at week 26 and week 52 for patients treated with PLX-PAD (n=120), in the injured leg (p=0.047, p=0.0022) and uninjured leg (p=0.073, p=0.0046) compared with placebo (n=120). This new data confirms the results demonstrated in Pluristem’s phase I/II study.
The study did not meet the primary endpoint, which was the Short Physical Performance Battery (SPPB) test at week 26. The SPPB is a series of physical performance tests used in older persons to assess lower extremity function and mobility.
PLX-PAD was well tolerated and demonstrated a significant increase in HAS, with patients showing an increase of 3.2kg from reference (week 6) to week 26 compared with 1.3kg in the placebo group, a 2kg difference (p=0.047) in the injured leg.
When comparing the absolute HAS between study groups (treated versus placebo) at week 52, patients treated with PLX-PAD showed a 2.6kg higher score than placebo treated patients in the injured leg (p=0.0511). A similar benefit was seen in the uninjured leg, with a 2.2kg difference (p=0.113).
The increase in HAS was further supported by a positive trend in a 6-minute walk test at week 52, showing an increase in walking distance, with the treated patients able to walk 296 metres versus only 266 metres in placebo treated patients. The 6-minute walk test evaluates the global and integrated responses of all the systems involved in walking (pulmonary, cardiovascular, systemic and peripheral circulation, musculoskeletal function, neuromuscular units, and muscle metabolism), and is an acceptable functional endpoint.
Professor Tobias Winkler from the Center for Musculoskeletal Surgery, Charité Berlin, and the principal investigator of the study, said: “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.
“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 .”
“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,” said Pluristem Chief Executive Officer and President, Yaky Yanay.
“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 .”