- Extended-Release Calcifediol: A Data Journey from Phase 3 Studies to Real-World Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism
- Asked Chat-GPT: Under what situations is Extended-Release Calcifediol beneficial?
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Extended-Release Calcifediol: A Data Journey from Phase 3 Studies to Real-World Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism
Nephron. 2024;148(10):657-666. doi: 10.1159/000538818
Domenico Merante 1, Henrik Schou 1, Isabelle Morin 1, Marius Manu 1, Akhtar Ashfaq 2, Charles Bishop 2, Stephen Strugnell 2
Background: Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI).
Summary: This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D (25(OH)D) and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled phase 3 per-protocol populations, 74% of the ERC cohort were uptitrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH.
Key messages: These data establish a "continuum" of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.
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Asked Chat-GPT: Under what situations is Extended-Release Calcifediol beneficial?
Treatment of Secondary Hyperparathyroidism (SHPT) in Chronic Kidney Disease (CKD):
ERC is approved for treating SHPT in patients with stage 3 and 4 CKD and vitamin D insufficiency. It has shown effectiveness in:
- Reducing parathyroid hormone (PTH) levels:
- In phase 3 clinical trials, 33-34% of patients achieved ≥30% reduction in PTH levels.
- In real-world settings, 40.2% of patients achieved ≥30% reduction in PTH.
- Increasing vitamin D levels:
- 70.1% of patients in real-world studies achieved 25(OH)D levels ≥30 ng/mL.
- 80.2-83.3% of patients in clinical trials reached this threshold.
Early Treatment of SHPT:
ERC is beneficial when initiated early in CKD progression:
- It is effective regardless of CKD stage (3 or 4) [34-36].
- Early initiation may delay SHPT progression and reduce long-term complications [34-36].
Patients with Vitamin D Insufficiency:
ERC is particularly useful in CKD patients with vitamin D insufficiency, as it effectively raises 25(OH)D levels [34-36].
Patients at Risk of Hypercalcemia:
ERC demonstrates a lower risk of hypercalcemia compared to activated vitamin D analogues:
- Only 1.8% of patients in real-world studies reported hypercalcemia.
- Mean changes in calcium levels were <3% in clinical trials.
Overweight CKD Patients:
ERC has shown effectiveness in raising serum total 25-hydroxyvitamin D levels even in overweight non-dialysis CKD patients with SHPT.In summary, ERC is beneficial for CKD patients with SHPT and vitamin D insufficiency, particularly when initiated early in disease progression. It offers advantages in terms of efficacy and safety profile compared to other treatment options for SHPT in CKD.