Clinical Information

Rayaldee^® (calcifediol) extended-release capsules helped significantly more patients with secondary hyperparathyroidism (SHPT) and stage 3 or 4 chronic kidney disease (CKD) to reduce intact parathyroid hormone (iPTH) by ≥30% from baseline and increase 25D to adequate levels (≥30 ng/mL), compared with placebo.¹

Rayaldee significantly increased 25D levels¹

Mean 25D levels over time in clinical trials¹*

In clinical trials 1 and 2, mean serum 25(OH)D levels increased gradually over 26 weeks in the treatment arms and was unchanged in the placebo arms (P<0.001).

	Mean Serum Total 25(OH)D, ng/mL
Week of treatment	Study 1: Rayaldee Arm	Study 2: Rayaldee Arm	Study 1: Placebo Arm	Study 2: Placebo Arm
0	19.846377	19.621849	19.252688	19.269444
4	33.315789	34.915254	19.016667	18.416667
8	40.695652	43.228814	19.290323	19.711864
10	42.424528	45.468468	17.982759	18.576923
12	45.504348	48.177966	18.193548	18.758621
16	57.823009	58.794872	17.786885	18.983333
20	65.04386	65.82906	17.66129	19.383333
22	66.407407	67.06422	17.912281	19.578947
24	68.473214	67.324786	18.137931	19.372881
26	67.773913	69.222222	17.393443	19.982456

Increased 25D levels were associated with corresponding increases in 1,25D levels²

Evaluating treatment options

*	Mean data from patient clinical trials do not guarantee individual results.

Increased 25D levels were associated with corresponding increases in 1,25D levels²

Evaluating treatment options

Patients achieving target 25D levels (≥30 ng/mL) at week 26¹

In clinical trial 1, 80% of patients in the treatment arm achieved target 25(OH)D levels of ≥30 ng/mL at week 26 versus 3% of patients in the placebo arm. In clinical trial 2, 83% of patients in the treatment arm achieved target 25(OH)D levels of ≥30 ng/mL at week 26 versus 7% of patients in the placebo arm.

Average steady-state 25D levels ≥50 ng/mL

Why is 50 ng/mL important?

Average steady-state 25D levels ≥50 ng/mL

Why is 50 ng/mL important?

Rayaldee effectively reduced intact parathyroid hormone¹

Mean iPTH levels over time in clinical trials*

In both clinical trials, spanning 26 weeks, iPTH declined in patients in the treatment arm. iPTH did not decline in patient in the placebo arm.

	Mean Plasma iPTH, pg/ml
Week of treatment	Study 1: Rayaldee Arm	Study 2: Rayaldee Arm	Study 1: Placebo Arm	Study 2: Placebo Arm
0	144.43	142.9	136.91	153.91
4	134.09	128.43	133.46	152.59
8	126.83	124.74	142.28	160.55
10	123.78	122.88	142.42	167.31
12	122.95	122.48	140.47	169.05
16	120.86	113.75	144.32	162.83
20	109.29	110.14	145.74	155.42
22	107.44	121.9	148.42	148.07
24	105.04	115.56	139.82	162.33
26	113.25	110.88	148.72	166.4

iPTH levels declined over time with Rayaldee compared to placebo (P<0.001)¹*

Does BMI matter?

*	Mean data from patient clinical trials do not guarantee individual results.

iPTH levels declined over time with Rayaldee compared to placebo (P<0.001)¹*

Does BMI matter?

Mean iPTH change from baseline^1,2

In both clinical trials, which spanned 26 weeks, the mean iPTH declined from baseline patients in the treatment arm. The mean iPTH did not change from baseline in patient in the placebo arm. P<0.001.

	Percent Change From Baseline
Week of treatment	Rayaldee Arm	Placebo Arm
0	0	0
4	-8.04	-1.4
8	-11.81	4.59
10	-12.95	4.3
12	-13.62	3.26
16	-18.01	5.2
20	-22.84	2.4
22	-19.9	1.67
24	-23.64	3.82
26	-21.99	9.43

Patients achieving iPTH response (≥30% change from baseline to end of trial)¹*

	Study 1 (N=213)	Study 2 (N=216)
Rayaldee arm (% of patients)	33	34
Placebo arm (% of patients)	8	7

*	Average of weeks 20, 22, 24, and 26.

The effect of Rayaldee on serum calcium and phosphorus was similar to placebo¹*

Mean serum calcium over time in clinical trials^1†

In clinical trials 1 and 2, mean serum calcium levels did not significantly change compared to placebo over 26 weeks of treatment. There was not a significant difference in serum calcium levels during the extension trial, which spanned weeks 26-52 and in which patients who had recieved placebo transitioned to Rayaldee.

	Mean Serum Calcium, mg/dL
Week of treatment	Study 1: Rayaldee Arm	Study 2: Rayaldee Arm	Study 1: Placebo Arm	Study 2: Placebo Arm
0	9.18826	9.23754	9.23898	9.25583
4	9.11304	9.15932	9.20333	9.09138
8	9.18596	9.28151	9.14194	9.12833
10	9.18302	9.28364	9.21034	9.20385
12	9.34912	9.37863	9.30968	9.30172
16	9.30088	9.34492	9.22333	9.19667
20	9.36283	9.41111	9.28226	9.2931
22	9.31101	9.32547	9.25179	9.31071
24	9.37117	9.46842	9.27167	9.31186
26	9.46	9.54017	9.34262	9.35614

Participants in Study 2 were offered the opportunity to continue into an extension study. Patients who had been in the Rayaldee arm remained on study medication. Patients who had been in the placebo arm started treatment with Rayaldee.

	Mean Serum Calcium, mg/dL
Week of treatment	Study 2 Extension: Rayaldee Continuation	Study 2 Extension: Placebo to Rayaldee
26	9.47879	9.34382
30	9.40061	9.28764
34	9.38765	9.24333
36	9.39878	9.34886
38	9.50183	9.39778
42	9.55565	9.47614
46	9.4672	9.46444
50	9.55403	9.44494
52	9.57561	9.49663

^†	Mean data from patient clinical trials do not guarantee individual results.

There was no significant difference in serum calcium or phosphorus levels during the extension trial, in which patients who had received placebo transitioned to Rayaldee.¹*

What about real-world performance?

Mean serum phosphorus over time in clinical trials^1†

In clinical trials 1 and 2, mean serum calcium levels did not significantly change compared to placebo over 26 weeks of treatment. There was not a significant difference in serum calcium levels during the extension trial which spanned weeks 26-52 and in which patients who were on placebo transitioned to Rayaldee.

	Mean Serum Phosphorus, pg/ml
Week of treatment	Study 1: Rayaldee Arm	Study 2: Rayaldee Arm	Study 1: Placebo Arm	Study 2: Placebo Arm
0	3.72188	3.78333	3.80054	3.63167
4	3.8287	3.86134	3.81667	3.78833
8	3.81053	3.97479	3.90161	3.84667
10	3.90566	3.91532	3.89828	3.78462
12	3.84561	3.88291	3.8129	3.82203
16	3.87456	4.0161	3.90333	3.735
20	3.84779	4.02712	3.82581	3.76552
22	3.89908	4.01963	3.92281	3.74464
24	3.9	4.01316	4.01667	3.79322
26	3.89565	4.02991	3.85574	3.71404

	Mean Serum Phosphorus, mg/dL
Week of treatment	Study 2 Extension: Rayaldee Continuation	Study 2 Extension: Placebo to Rayaldee
26	3.99879	3.8618
30	3.97378	3.85111
34	3.95366	3.82444
36	3.97455	3.90909
38	4.00427	3.87556
42	3.9896	3.91444
46	3.8928	3.85889
50	4.0216	3.96222
52	3.89758	3.9809

^†	Mean data from patient clinical trials do not guarantee individual results.

Patients randomized to Rayaldee had a greater mean (SE) increase in calcium and phosphorus than patients randomized to placebo (Calcium: Rayaldee 0.2 [0.02] mg/dL versus placebo 0.1 [0.03] mg/dL [P<0.001]; Phosphorus: Rayaldee 0.2 [0.03] mg/dL versus placebo 0.1 [0.04] mg/dL). A total of 4.2% of Rayaldee-treated subjects and 2.1% of placebo-treated subjects had at least 1 elevation in calcium above the upper limit of normal (10.5 mg/dL). A total of 45% of Rayaldee-treated subjects and 44% of placebo-treated subjects had at least 1 elevation in phosphorus above the upper limit of normal (4.5 mg/dL).¹

Clinical trials have demonstrated a safety profile for Rayaldee similar to placebo^1,2

Common Adverse Reactions in Phase 3 Placebo-Controlled Trials Reported in ≥1.4% of Rayaldee-Treated Subjects

Adverse Reactions	Placebo (n=144) %	Rayaldee (n=285) %
Anemia	3.5	4.9
Nasopharyngitis	2.8	4.9
Blood creatinine increased	1.4	4.9
Dyspnea	2.8	4.2
Cough	2.1	3.5
Cardiac failure congestive	0.7	3.5
Constipation	2.8	3.2
Bronchitis	0.7	2.8
Hyperkalemia	0.7	2.5
Osteoarthritis	0.7	2.1
Hyperuricemia	0.7	1.8
Contusion	0.0	1.8
Pneumonia	0.7	1.4
Chronic obstructive pulmonary disease	0.0	1.4

Study design

^a	Serum total 25D levels between 10 and 30 ng/mL.
^b	Subjects stratified by CKD.
^c	Dose kept at 30 mcg or increased to 60 mcg for last 14 weeks if iPTH level >70 pg/mL, serum 25D level <65 ng/mL and serum calcium level <9.8 mg/dL.

Abbreviations: 1,25D, 1,25-dihydroxyvitamin D; 25D, 25-hydroxyvitamin D; CKD, chronic kidney disease; CV, cardiovascular; iPTH, intact parathyroid hormone; SHPT, secondary hyperparathyroidism.

References: 1. Sprague SM, Crawford PW, Melnick JZ, et al. Use of extended-release calcifediol to treat secondary hyperparathyroidism in stages 3 and 4 chronic kidney disease. Am J Nephrol. 2016;44(4):316-325. doi:10.1159/000450766 2. Rayaldee. Prescribing information. OPKO Pharmaceuticals, LLC; 2024.

Clinical Information

Rayaldee significantly increased 25D levels¹

Mean 25D levels over time in clinical trials¹*

Evaluating treatment options

Evaluating treatment options

Patients achieving target 25D levels (≥30 ng/mL) at week 26¹

Why is 50 ng/mL important?

Why is 50 ng/mL important?

Rayaldee effectively reduced intact parathyroid hormone¹

Mean iPTH levels over time in clinical trials*

Does BMI matter?

Does BMI matter?

Mean iPTH change from baseline^1,2

Patients achieving iPTH response (≥30% change from baseline to end of trial)¹*

The effect of Rayaldee on serum calcium and phosphorus was similar to placebo¹*

Mean serum calcium over time in clinical trials^1†

What about real-world performance?

Mean serum phosphorus over time in clinical trials^1†

Clinical trials have demonstrated a safety profile for Rayaldee similar to placebo^1,2

Common Adverse Reactions in Phase 3 Placebo-Controlled Trials Reported in ≥1.4% of Rayaldee-Treated Subjects

Study design

Important Safety Information

Indication and Limitations of Use

Important Safety Information

Clinical Information

Rayaldee significantly increased 25D levels1

Mean 25D levels over time in clinical trials1*

Evaluating treatment options

Evaluating treatment options

Patients achieving target 25D levels (≥30 ng/mL) at week 261

Why is 50 ng/mL important?

Why is 50 ng/mL important?

Rayaldee effectively reduced intact parathyroid hormone1

Mean iPTH levels over time in clinical trials*

Does BMI matter?

Does BMI matter?

Mean iPTH change from baseline1,2

Patients achieving iPTH response (≥30% change from baseline to end of trial)1*

The effect of Rayaldee on serum calcium and phosphorus was similar to placebo1*

Mean serum calcium over time in clinical trials1†

What about real-world performance?

Mean serum phosphorus over time in clinical trials1†

Clinical trials have demonstrated a safety profile for Rayaldee similar to placebo1,2

Common Adverse Reactions in Phase 3 Placebo-Controlled Trials Reported in ≥1.4% of Rayaldee-Treated Subjects

Study design

Important Safety Information

Indication and Limitations of Use

Important Safety Information

Rayaldee significantly increased 25D levels¹

Mean 25D levels over time in clinical trials¹*

Patients achieving target 25D levels (≥30 ng/mL) at week 26¹

Rayaldee effectively reduced intact parathyroid hormone¹

Mean iPTH change from baseline^1,2

Patients achieving iPTH response (≥30% change from baseline to end of trial)¹*

The effect of Rayaldee on serum calcium and phosphorus was similar to placebo¹*

Mean serum calcium over time in clinical trials^1†

Mean serum phosphorus over time in clinical trials^1†

Clinical trials have demonstrated a safety profile for Rayaldee similar to placebo^1,2