Extended-Release Calcifediol: A Data Journey from Phase 3 Studies to Real-World Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism (SHPT)

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 or 4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Methods: In this descriptive analysis, laboratory parameters of SHPT-CKD stage 3-4 subjects randomised to ERC in two phase 3 clinical studies (NCT01651000 [N=141] and NCT01704079 [N=144]) were compared with those treated with ERC in a RWE study (MBD-AWARE study; N=174]). Results: The main baseline laboratory parameters showed consistency between the phase 3 studies and the RWE study, except for baseline parathyroid hormone (PTH). Mean±standard deviation baseline PTH levels were 147±56 pg/mL and 148±64 pg/mL in the intent-to-treat populations on ERC in NCT01651000 and NCT01704079, respectively, and 181±98 pg/mL in the RWE study. Moreover, in the RWE study, 53% of subjects receiving ERC had CKD stage 4 with an even higher baseline PTH level versus stage 3 CKD subjects. ERC treatment significantly reduced PTH levels and increased 25-hydroxyvitamin D [25(OH)D], regardless of CKD stage, in all 3 studies. In the phase 3 per-protocol populations, 74% of subjects treated with ERC were up-titrated to 60 μg daily after 12 weeks at 30 μg daily, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% reductions in PTH. In contrast, based on an apparent ‘wait longer approach’ to test key markers of SHPT, only 2% of subjects in the RWE study were up-titrated. Nevertheless, 70% of subjects achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH, consistent with the phase 3 results. Conclusions: These data suggest a ‘continuum’ of clinical evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage. A clinically relevant response was observed with ERC in the RWE study, consistent with the phase 3 studies, despite higher baseline PTH levels and lower ERC dose. In summary, these data support early treatment initiation with ERC, following diagnosis of SHPT, VDI and stage 3 CKD, to delay the progression of SHPT. Funding: Commercial Support - CSL Vifor