Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial.

Conventional therapy for hypoparathyroidism consisting of active vitamin D and calcium aims to alleviate hypocalcemia but fails to restore normal parathyroid hormone (PTH) physiology. PTH replacement therapy is the ideal physiologic treatment for hypoparathyroidism. The double-blind, placebo-controlled, 26-week, phase 3 PaTHway trial assessed the efficacy and safety of PTH replacement therapy for hypoparathyroidism individuals with the investigational drug TransCon PTH (palopegteriparatide). Participants (n = 84) were randomized 3:1 to once-daily TransCon PTH (initially 18 µg/d) or placebo, both co-administered with conventional therapy. The study drug and conventional therapy were titrated according to a dosing algorithm guided by serum calcium. The composite primary efficacy endpoint was the proportion of participants at week 26 who achieved normal albumin-adjusted serum calcium levels (8.3-10.6 mg/dL), independence from conventional therapy (requiring no active vitamin D and ≤600 mg/d of calcium), and no increase in study drug over 4 weeks before week 26. Other outcomes of interest included health-related quality of life measured by the 36-Item Short Form Survey (SF-36), hypoparathyroidism-related symptoms, functioning, and well-being measured by the Hypoparathyroidism Patient Experience Scale (HPES), and urinary calcium excretion. At week 26, 79% (48/61) of participants treated with TransCon PTH versus 5% (1/21) wiplacebo met the composite primary efficacy endpoint (p < 0.0001). TransCon PTH treatment demonstrated a significant improvement in all key secondary endpoint HPES domain scores (all p < 0.01) and the SF-36 Physical Functioning subscale score (p = 0.0347) compared with placebo. Additionally, 93% (57/61) of participants treated with TransCon PTH achieved independence from conventional therapy. TransCon PTH treatment normalized mean 24-hour urine calcium. Overall, 82% (50/61) treated with TransCon PTH and 100% (21/21) wiplacebo experienced adverse events; most were mild (46%) or moderate (46%). No study drug-related withdrawals occurred. In conclusion, TransCon PTH maintained normocalcemia while permitting independence from conventional therapy and was well-tolerated in individuals with hypoparathyroidism. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results.

PURPOSE: The objectives of the ongoing, Phase 3, open-label extension trial enliGHten are to assess the long-term safety and efficacy of weekly administered long-acting growth hormone lonapegsomatropin in children with growth hormone deficiency. METHODS: Eligible subjects completing a prior Phase 3 lonapegsomatropin parent trial (heiGHt or fliGHt) were invited to participate. All subjects were treated with lonapegsomatropin. Subjects in the United States switched to the TransCon hGH Auto-Injector when available. Endpoints were long-term safety, annualized height velocity, pharmacodynamics [insulin-like growth factor-1 SD score (SDS) values], and patient- and caregiver-reported assessments of convenience and tolerability. RESULTS: Lonapegsomatropin treatment during enliGHten was associated with continued improvements in height SDS through week 104 in treatment-naïve subjects from the heiGHt trial (-2.89 to -1.37 for the lonapegsomatropin group; -3.0 to -1.52 for the daily somatropin group). Height SDS also continued to improve among switch subjects from the fliGHt trial (-1.42 at fliGHt baseline to -0.69 at week 78). After 104 weeks, the average bone age/chronological age ratio for each treatment group was 0.8 (0.1), showing only minimal advancement of bone age relative to chronological age with continued lonapegsomatropin treatment among heiGHt subjects. Fewer local tolerability reactions were reported with the TransCon hGH Auto-Injector compared with syringe/needle. CONCLUSIONS: Treatment with lonapegsomatropin continued to be safe and well-tolerated, with no new safety signals identified. Children treated with once-weekly lonapegsomatropin showed continued improvement of height SDS through the second year of therapy without excess advancement of bone age.