RESTEM’s ULSC Therapy Restem-L Fast Tracked by FDA for Idiopathic Inflammatory Myopathy
Restem-L previously received orphan drug designation from the FDA for PM/DM in December 2024.
RESTEM’s Restem-L, an investigational umbilical cord outer lining stem cells (ULSCs) product, has been granted fast track designation by the FDA for idiopathic inflammatory myopathy (IIM, also known as polymyositis and dermatomyositis, PM/DM).1
Notably, Restem-L previously received orphan drug designation from the FDA for PM/DM in December 2024.2 The therapy has been evaluated in a phase 1 clinical trial (NCT04723303) for adults with PM/DM that took place in Gainesville, Florida, and was completed on March 8, 2024.
“Receiving fast track designation for our ULSC program in IIM, followed by the recent orphan drug designation, underscores the need for a change in the treatment paradigm and highlights the importance of developing novel therapeutic options for patients with IIM,” Andres Isaias, the chief executive officer of RESTEM, said in a statement.1 “The recently presented phase 1 data demonstrated that treatment with our Restem-L led to 78% clinical improvement and a 35% reduction in steroid usage within 6 months. With the fast track designation, Restem-L could benefit from accelerated approval pathway, priority reviews, and rolling submissions, allowing us to bring this potentially life-changing treatment to IIM patients sooner. We look forward to advancing the Restem-L program development and initiating IIMPACT, a potentially registrational phase 2/3 clinical trial in IIM in Q1 2025.”
Data from the phase 1 trial were presented at the 2024 American College of Rheumatology (ACR) Convergence, held November 14 to 19, in Washington, DC.3 According to the abstract, authored by Michael R. Bubb, MD, a rheumatologist at University of Florida Health, and colleagues, 9 patients completed the trial. With regard to safety, 1 treatment-related adverse event (AE) was reported, a case of flushing reaction that happened during the first patient’s infusion of the therapy. In response to the AE, the infusion was paused to provide 150 mg of hydrocortisone, after which the AE did not recur upon resumption of infusion.
Within 6 months of infusion, 6 of the 9 patients had achieved a total improvement score (TIS) of at least 40%, thus meeting the criteria for “moderate improvement.” Furthermore, 7 of 9 patients achieved a TIS of at least 20, thus meeting the criteria for “significant improvement.” In addition, at 6 months posttreatment, patients in the trial demonstrated an improvement of almost 10 points from baseline in Manual Muscle Testing (MMT8), jumping to 68 ± 4 at 6 months posttreatment from 59 ± 4 at baseline (mean ± SEM, P < 0.001). Bubb and colleagues also noted that excluding 1 patient who did not respond by TIS and who had a flare that was treated with corticosteroids, the remaining 8 patients showed a 35% reduction in average prednisone dosage at 6 months posttreatment.
“Mesenchymal stem/stromal cells are self-renewing, multi-potent stromal cells which act as modulators of immune responses,” Bubb and colleagues wrote in the abstract.3 Umbilical cord-derived mesenchymal stromal cells, a classification of cells that includes ULSC may be associated with a younger cellular phenotype with minimal expression of HLA-DR after activation, which is expected to correlate with reduced immunogenic potential... Taken together, the overall human experience with the intravenous infusion of ULSC has demonstrated an absence of adverse outcomes attributable to this investigational product, and in the context of DM/PM, has demonstrated early evidence of clinical improvement in multiple participants using complementary outcome measures, in the context of progressive reduction in steroid dosing.”
