Abstract #1408044: Long-term Efficacy and Safety of TransCon PTH from Phase 2 PaTH Forward Trial in Adults with Chronic Hypoparathyroidism

Hypoparathyroidism is a rare disease characterized by parathyroid hormone (PTH) insufficiency. Conventional therapy (active vitamin D and calcium [Ca]) targets short-term symptoms, but fails to restore normal PTH physiology. TransCon PTH is an investigational prodrug with sustained release of PTH in development for the treatment of adults with chronic hypoparathyroidism. In the phase 2 PaTH Forward trial of TransCon PTH, 82% of participants achieved independence from conventional therapy at Week 4, which was sustained through Week 84. Here we report long-term efficacy and safety through Week 110 in the PaTH Forward trial. PaTH Forward is a randomized, double-blinded, placebo-controlled phase 2 trial investigating the efficacy and safety of TransCon PTH in adults with chronic hypoparathyroidism. Co-administered with conventional therapy, participants received 4 weeks of fixed-dose TransCon PTH (15, 18, or 21 μg/day once daily, subcutaneous injection) or placebo. This was followed by an open-label extension period planned through Week 214, in which TransCon PTH and conventional therapy were titrated to maintain normocalcemia. At Week 110, 96.6% (57/59) participants continued in the trial. At baseline, the mean age of participants was 50 years (range: 25-76), and 81% were female, and mean 24-hr urine Ca was 428 mg. At Week 110, 93.0% (53/57) of participants were independent from conventional therapy (taking no active vitamin D and ≤ 600 mg/day elemental calcium). During treatment with TransCon PTH, average (standard deviation [SD]) values for serum Ca remained in the normal range at Week 26 (8.9 [0.5] mg/dL) through Week 110 (8.6 [0.6] mg/dL). For the overall study population, mean 24-hour urine Ca normalized at Week 26 (173 mg/24-hr), and was maintained in the normal range through Week 110 (167 mg/24-hr). The majority of treatment-emergent adverse events (TEAEs) were mild and assessed unrelated to study drug, no TEAEs led to study discontinuation, and no TEAEs of hypo- or hypercalcemia required visits to the emergency room or hospitalization. In the PaTH Forward trial, 93.0% of participants maintained independence from conventional therapy through Week 110 of TransCon PTH therapy. TransCon PTH was well-tolerated through Week 110. These data support the potential long-term clinical benefit of TransCon PTH in adults with chronic hypoparathyroidism.