FDA Approves Palopegteriparatide for Treatment of Hypoparathyroidism
Palopegteriparatide is a prodrug of parathyroid hormone designed to provide continuous exposure of the hormone over a 24-hour dosing period.
Updated at 12:00 pm on August 12, 2024.
The FDA has approved palopegteriparatide (Yorvipath; Ascendis Pharma) for the treatment of hypoparathyroidism in adults. The approval marks the first and only treatment for this indication. Palopegteriparatide is a prodrug of parathyroid hormone designed to provide continuous exposure of the hormone over a 24-hour dosing period.1
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“The consequences of hypoparathyroidism on the health and quality of life of our patients can be extraordinarily debilitating,” Lynn Kohlmeier, MD, endocrinologist at Spokane Osteoporosis & Endocrinology and chair of the medical advisory board of the HypoPARAthyroidism Association, said in a news release. “The ability to address the underlying cause of this disease is crucial and will be an important advancement for our patients with hypoparathyroidism.”1
The approval is based on evidence from the global phase 2 PaTH Forward (NCT04009291) and phase 3 PaTHway (NCT04701203) trials, according to the news release.1
PaTH Forward was multicenter, randomized, double-blind trial consisting of 4 weeks with an open-label extension spanning through week 214, evaluating the daily administration of palopegteriparatide and the effect on active vitamin D and/or calcium for patients. Investigators included adults aged 18 years and older with a body mass index of 17 to 40 and postsurgical, autoimmune, genetic, idiopathic hypoparathyroidism. Individuals received randomized treatment of either palopegteriparatide 15 µg, 18 µg, or 21 µg per day or the placebo, according to the study investigators.2
A total of 104 individuals were screened, with 57 included in the 4-week analysis. Approximately 50% who were treated with the study drug achieved the primary end point, based on serum calcium within normal range, fractional excretion of calcium, discontinuation of all active vitamin D supplements, and reduction of calcium supplementation less than or equal to 100 mg/day, compared with 15% dosed with the placebo. At week 4, investigators noted that 82% of patients receiving the study drug stopped oral active vitamin D and reduced calcium supplementation compared with 15% of those receiving the placebo. Further, 50% achieved complete independence from conventional therapy compared with 0%, respectively.2
There were 82 individuals who received at least 1 dose of the study drug in the PaTHway trial, according to the investigators, with 79 completing blinded treatment through week 26 and 78 through week 52. During the blinded period, treatment with palopegteriparatide reduced elemental calcium doses and complete discontinuation of active vitamin D with 8 weeks, with 81% of those treated with the drug (through week 52) meeting the multicomponent efficacy end point. Further, 95% achieved independence from conventional therapy.3
Treatment with palopegteriparatide also resulted in statistically significant estimated glomerular filtration rate (eGFR) improvements during the 26-week blinded period. For safety, investigators reported treatment-emergent adverse events being reported similarly for individuals who had baseline eGFR less than 60 and greater or equal to 60 mL/min/1.73 m2. There was 1 case of nephrolithiasis reported for those in the placebo group during blinded treatment and none in the palopegteriparatide group.3
