Parathyroid hormone therapy normalizes calcium for most with hypoparathyroidism
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Key takeaways:
- At 52 weeks, 81% of adults receiving palopegteriparatide had normalized serum calcium levels without needing conventional therapy.
- Mean bone mineral density scores remained normal at 1 year.
The majority of adults with hypoparathyroidism achieved normal serum calcium levels with palopegteriparatide at 1 year without supplemental vitamin D or calcium, according to data from a phase 3 open-label extension.
As Healio previously reported, the FDA approved palopegteriparatide (Yorvipath, Ascendis Pharma), a parathyroid hormone prodrug, in August for the treatment of hypoparathyroidism. In a phase 2 open-label extension trial, 77% of participants required no calcium or vitamin D supplementation at 110 weeks of palopegteriparatide therapy. New findings published in The Journal of Clinical Endocrinology & Metabolism revealed the medication also provided long-term benefits for participants in the phase 3 PaTHway open-label extension study.
“Serum calcium and urine calcium were maintained long term in the desired goal ranges in patients with hypoparathyroidism,” Bart L. Clarke, MD, professor of medicine in the division of endocrinology, metabolism, diabetes and nutrition at the Mayo Clinic in Rochester, Minnesota, told Healio. “These values are very difficult to control with just calcium and calcitriol in many patients with hypoparathyroidism.”
In a phase 3 randomized controlled trial, 82 adults with hypoparathyroidism were randomly assigned to once-daily palopegteriparatide or placebo for 26 weeks (mean age, 48.6 years; 78% women; 93% white). At 26 weeks, adults were invited to continue into an open-label extension where all participants would receive palopegteriparatide up to 156 weeks. The study included data up to 52 weeks. The primary efficacy outcome was the percentage of adults achieving an albumin-adjusted serum calcium level between 8.3 mg/dL and 10.6 mg/dL without active vitamin D or calcium therapy.
Therapy normalizes calcium for most
Of the trial participants, 78 continued into the open-label extension and completed the 52-week follow-up visit. At 52 weeks, 81% of adults achieved a normal albumin-adjusted serum calcium level without the need of conventional therapy, and 95% achieved independence from conventional therapy. No participants were taking active vitamin D at 52 weeks. The mean elemental calcium dose at 52 weeks was 148 mg per day, with 61 participants taking no elemental calcium, 13 taking 600 mg a day and four taking 600 mg or more a day. Adults who received placebo in the first 26 weeks increased serum calcium levels from 8.2 mg/dL at 26 weeks to 9.1 mg/dL at 52 weeks after starting palopegteriparatide.
Adults who initially received placebo and switched to palopegteriparatide had improvements in the Hypoparathyroidism Patient Experience Scale and the 36-item Short-Form Health Survey from 26 to 52 weeks, similar to what occurred among the treatment group during the trial’s blinded portion.
Among adults randomly assigned to palopegteriparatide at baseline, P1NP level increased from 33.8 ng/mL at baseline to 116.5 ng/mL at 26 weeks before dropping to 84.4 ng/mL at 52 weeks. Median CTx levels increased from 180 ng/L at baseline to 1,040 ng/L at 12 weeks before falling to 640 ng/L at 52 weeks. The change in bone turnover markers among the placebo group was similar after switching to palopegteriparatide therapy.
Mean bone mineral density (BMD) T- and Z-scores were normal at all sites at 52 weeks. Participants randomly assigned to palopegteriparatide had a BMD decrease of 8.1% at the lumbar spine, 6.5% at the total hip and 7% at the femoral neck from baseline to 26 weeks. From 26 to 52 weeks, the same group of adults had a 0.6% decrease in lumbar spine BMD, a 1.5% decline in total hip BMD and a 1.5% drop in femoral neck BMD. The decrease in distal one-third radius BMD was 0.06% from baseline to 26 weeks and 0.5% from 26 to 52 weeks.
“This paper supports the effectiveness and safety of use of palopegteriparatide for treatment of chronic hypoparathyroidism,” Clarke told Healio. “It currently is the only FDA-approved form of [parathyroid hormone] available to treat this disorder.”
Safety data
Treatment-emergent adverse events occurred in 53% of the study participants. Injection site reactions were most common and occurred among 26% of adults. Other treatment-emergent adverse events reported in more than 5% of participants included hypercalcemia (14%), nausea (9%), headache (8%) and hypocalcemia (5%).
Two adults had serious adverse events related to palopegteriparatide. Both of those events were due to hypercalcemia from accidental deviations in the dose titration algorithm, and both participants continued treatment after the events were resolved, the researchers wrote.
More long-term studies of palopegteriparatide are expected in the future, and the open-label extension is scheduled to continue up to 156 weeks, according to Clarke.
For more information:
Bart Clarke, MD, can be reached at clarke.bart@mayo.edu.
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