Ascendis Pharma (ASND) Study result presentation summary

Mechanism and rationale for therapy

• PTH is the primary regulator of calcium and phosphate balance, acting on bone, kidney, and indirectly on the intestine to maintain homeostasis.

• Conventional therapy for hypoparathyroidism alleviates symptoms but does not restore normal PTH physiology.

• PTH replacement aims to normalize serum and urine calcium and phosphate, improve skeletal health, and enhance quality of life.

Palopegteriparatide (YORVIPATH; TransConⓇ PTH) profile

• Palopegteriparatide is a once-daily prodrug of PTH (1-34) that delivers active PTH within the physiological range for 24 hours.

• It has received regulatory approval in the EU, US, and several other countries for adults with chronic hypoparathyroidism.

PaTHway Phase 3 trial design and endpoints

• 82 adults with hypoparathyroidism were randomized to palopegteriparatide or placebo, with a double-blind period followed by an open-label extension to 156 weeks.

• Efficacy endpoints included independence from active vitamin D and calcium, normal serum calcium, and patient-reported outcomes.

• Safety endpoints included 24-hour urine calcium and incidence of adverse events.