Spur Therapeutics’ Gene Therapy SBT101 Generally Well-Tolerated in Phase 1 Trial for Adrenoleukodystrophy
The new data were presented in a poster at ASGCT’s 2025 meeting.
Spur Therapeutics’ SBT101, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat X-linked adrenoleukodystrophy (ALD), was deemed “generally well-tolerated" in new safety data from the ongoingphase 1/2 PROPEL clinical trial (NCT05394064).1 The data were presented in a poster at the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2024, in New Orleans, LA.
The study results reported included 8 men with ages ranging from 19 to 36 years, 4 of whom had received a lower dose of SBT101 (1.0x1014 vg, cohort 1) and 4 of whom had received a higher dose of SBT101 (3.0x1014 vg, cohort 2). As of the April 21, 2025, data cut off, the most frequently reported treatment-emergent adverse events (TEAEs), defined as those with 3 or more events having occurred across all patients, were headache, muscular weakness, muscoskeletal stiffness, micturition urgency, interferon gamma assay positive, back pain, influenza, acne, asthenia, fatigue, insomnia, and paraesthesia.
In cohort 1, 3 patients (75%) experienced at least 1 serious TEAE, with 5 total serious TEAEs having occurred in this cohort. The serious TEAEs included gastroenteritis, pyelonephritis, muscular weakness, myelitis transverse, and aspiration. In cohort 2, only 1 patient (25%) experienced a single serious TEAE, a case of deep vein thrombosis, with the other patients in the cohort having not experienced any serious TEAEs.
Notably, 2 patients in the study experienced cerebral ALD conversion/progression. One of these patients, a 20-year-old patient dosed in cohort 1, showed gradual cerebral disease progression and systemic complications over the course of 10 months. The patient died at home, and his death was attributed to acute aspiration. An autopsy confirmed adrenomyeloneuropathy/cALD and the patient’s death was deemed unrelated to the gene therapy product. In another patient, aged 36 years, who was dosed in cohort 2, MRI findings at 18 months posttreatment suggested early cerebral involvement. This patient continues to be neurologically stable.
First author Marc Engelen, MD, PhD, a neurologist and clinical researcher at Amsterdam University Medical Centers, and colleagues noted that there were no clinically significant laboratory abnormalitiesobserved. Although, 2 patients in cohort 1 showed alanine transaminase levels more than 2 times greater than their baseline and 1 patient in cohort 2 showed creatinine levels more than 2 times greater than baseline.
“SBT101 was generally well-tolerated at both low and high dose levels evaluated...” Engelen and colleagues wrote in the poster.1 “Common TEAEs were mild to moderate and were consistent with common or expected events related to disease and immunosuppression used in the study. [There was] no clear dose-response relationship with regards to safety. Serious AEs were more frequent in the low dose cohort (3 of 4) compared to the high dose cohort (1 of 4)... Vector DNA shedding peaked early and cleared in blood and saliva within approximately 30 to 90 days. All urine samples were consistently below the lower limit of qualification.”
Notably, Spur Therapeutics previously operated under the name Freeline Therapeutics but made the change to its current name last year.2 Alongside this announcement, the company announced that it had purchased Swan Bio, a previously independent company that had been developing SBT101. At the time, Syncona, the founding shareholder for both original companies, contributed $50 million to the newly combined company.
“We see great promise across Spur’s broadened pipeline, with a highly differentiated lead clinical program backed by compelling data and a second potentially first-in-class clinical asset,” Chris Hollowood, the CEO of Syncona and the chairman of the board of directors of Spur, said in a June 2024 statement.2 “Building on its work, Spur has an exciting opportunity to become a leading gene therapy company developing one-time treatments for debilitating chronic diseases, potentially setting new standards of care and changing lives."
