Ascendis Pharma has announced promising long-term data from its Phase 2 PaTH Forward Trial, demonstrating that TransCon PTH (palopegteriparatide) continues to provide durable benefits for adults with hypoparathyroidism after more than four years of treatment. The results were presented at the joint congress of the European Society for Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE) by Dr. Andrea Palermo from Campus Bio-Medico University in Rome.
The data, collected at Week 214 of the trial, showed that 95% of the original 59 patients remained in the open-label extension portion of the study, indicating strong patient retention. Nearly all participants (98%) maintained normal albumin-adjusted serum calcium levels, and 93% remained independent from conventional therapy, defined as taking less than 600mg/day of calcium and no active vitamin D supplements.
Sustained Improvements in Multiple Clinical Parameters
The trial assessed several key clinical parameters throughout the treatment period. Bone turnover markers, including C-terminal telopeptide of type 1 collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP), increased from the low end of normal at baseline, peaked at Week 26, and then stabilized above baseline levels through Week 214. This pattern suggests a normalization of bone remodeling processes that are typically disrupted in hypoparathyroidism.
Bone mineral density (BMD), measured via DXA scan, remained within age- and sex-matched norms throughout the study period, indicating that the treatment did not adversely affect bone health despite the changes in bone turnover markers.
Particularly notable were the improvements in kidney function, with 67.8% of participants experiencing a clinically meaningful increase in estimated glomerular filtration rate (eGFR) of at least 5 mL/min/1.73 m² from baseline. These improvements were evident as early as Week 4 and persisted through Week 214, suggesting that TransCon PTH may help mitigate the renal complications often associated with hypoparathyroidism.
"We set out to address the underlying cause of disease and are pleased to see this long-term data reinforcing the safety profile and durability of response in patients treated with TransCon PTH, including sustained normalization of skeletal dynamics and significant and sustained improvements in kidney function," said Dr. Aimee Shu, Executive Vice President of Endocrine & Rare Disease Medical Science and Chief Medical Officer at Ascendis Pharma.
Safety Profile Remains Favorable
The safety profile of TransCon PTH remained consistent with previous reports. Treatment-emergent adverse events (TEAEs) were predominantly mild or moderate in severity, with no serious TEAEs or discontinuations related to the study drug. Safety assessments included monitoring of 24-hour urine-calcium levels, an important parameter for patients with hypoparathyroidism.
Study Design and Background
The PaTH Forward Trial was designed with a 4-week randomized, double-blind, placebo-controlled period followed by an open-label extension period that continues through Week 266. The current data represents findings at Week 214, providing one of the longest follow-up periods for a hypoparathyroidism treatment study.
Hypoparathyroidism is an endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), which regulates calcium and phosphate balance in the body. The condition affects bone, kidney, and intestinal function, and can lead to severe complications including neuromuscular irritability, renal issues, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for 70-80% of cases, with the remainder attributed to autoimmune and idiopathic causes.
Current standard treatments focus on managing symptoms rather than addressing the underlying hormone deficiency. These typically include high doses of calcium and active vitamin D supplements, which can lead to long-term complications including kidney damage and soft tissue calcification.
TransCon Technology Platform
TransCon PTH represents an application of Ascendis Pharma's proprietary TransCon technology platform, which is designed to create new therapies by combining the benefits of prodrug and sustained-release technologies. In the case of TransCon PTH, the technology enables a sustained release of active PTH, potentially mimicking the natural hormone's function more closely than conventional treatments.
The sustained positive results from this long-term study suggest that TransCon PTH may offer a significant advancement in the management of hypoparathyroidism, potentially addressing the underlying hormone deficiency rather than merely treating symptoms. This approach could represent a paradigm shift in the treatment of this rare endocrine disorder, offering patients the possibility of reduced dependence on conventional supplements while maintaining normal calcium levels and improving organ function.
As the trial continues toward its completion at Week 266, the medical community will be watching closely to see if these positive trends continue, potentially establishing TransCon PTH as a transformative therapy for patients with hypoparathyroidism.
