BridgeBio Pharma : BBIO - Encaleret - ADH1 - Primary Results from Phase 3 CALIBRATE Trial

Published: 2026-05-12 06:06:09 ET BBIO

Published on 05/12/2026 at 06:06 am EDT

‌Encaleret Restores Mineral Homeostasis in Autosomal Dominant Hypocalcemia Type 1 (ADH1): Primary Results from the Phase 3 CALIBRATE Trial

Presenting author: Prof. Filomena Cetani, Italy

BridgeBio

P Kamenický, M Mannstadt, S Ing, A Giustina, N Ito, AA Khan, MA Levine, T Ahmad, E Imel, L Rejnmark, M Warren, R Wermers, F Cetani, R Clifton-Bligh, A Kansara, S Lazarus, S Lemoine, A Palermo, JA Sayer, V Zikan, N Ma, M Rubin, J Turner, EFS van Velsen, ML Brandi, A Dmitrienko, K Ozono, P Tebben, MT Collins, MS Roberts, SH Adler, RI Gafni

‌Activating variants in the CASR cause Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Activating variants in the CASR

increase tissue sensitivity to Ca2+

Hypersensitive CaSR causes dysregulation of Ca homeostasis

Clinical Manifestations

PTH Secretion

Wild

Type

ADH1

Wild

Type

Blood Ca2+

PTH

Ca2+

Ca2+ Excretion

Ca2+

Conventional therapy with calcium and activated vitamin D does not correct the underlying pathophysiology and has the potential to worsen long-term complications

Tetany

Muscle cramps

Chronic Kidney Disease

BridgeBio

Roszko, et al. Front. Physiol. 2016.

Blood Ca2+

‌Phase 3 Study Design

Within-group comparison (randomized to encaleret)

Randomization 2:1

Participants randomized to encaleret stopped SoC prior to first dose

Between-treatment comparison (randomized to encaleret vs. SoC)

SoC Maintenance

Screening and SOC Optimization Period

Age > 16 years of age

Documented pathogenic variant, or variant of uncertain significance, of the CASR gene with biochemical findings of hypoparathyroidism

Encaleret Titration Period (N=45)

SoC Maintenance Period

Long-Term Extension 48 Months

Encaleret Maintenance Period

SoC Adjustment Period (N=22)

Period 1

4 Weeks

Period 2

20 Weeks

Period 3

4 Weeks

Proportion of participants achieving:

cCa1 within the target range of 2.08-2.68 mmol/L

24-hour urine Ca within the reference range (<7.0 mmol/day for men & <6.25 mmol/day for women)

1Albumin-corrected serum calcium.

Proportion of participants achieving iPTH above the lower limit of the reference range (key secondary)

1,25-(OH)2 Vitamin D, magnesium, and phosphate

Bone turnover markers

Renal ultrasound and renal function

SoC = standard of care; a combination of oral activated Vitamin D and/or calcium supplements. CASR = calcium-sensing receptor gene. iPTH = intact parathyroid hormone.

‌Baseline Characteristics

Characteristic

Target range

SoC (N=22)

Encaleret (N=45)

All Participants (N=67)

Age, yr, mean (range)

37 (16-63)

44 (16-76)

42 (16-76)

Female, n (%)

11 (50%)

24 (53%)

35 (52%)

Intact PTH, pmol/L, mean (SD)

1.6-6.9

0.63 (0.49)

0.71 (0.82)

0.68 (0.73)

Serum Calcium1, mmol/L, mean (SD)

2.08-2.68

1.97 (0.17)

2.09 (0.19)

2.05 (0.19)

24hr Urine Calcium, mmol/day, mean (SD)

<7.0(M)/6.25(W)

8.29 (4.89)

9.93 (4.44)

9.39 (4.62)

Phosphate, mmol/L, mean (SD)

0.81-1.55

1.63 (0.33)

1.54 (0.24)

1.57 (0.27)

Magnesium, mmol/L, mean (SD)

0.74-0.99

0.71 (0.06)

0.75 (0.07)

0.73 (0.07)

eGFR2, mL/min/1.73 m2, mean (range)

>60

77 (38-127)

83 (26-133)

79 (26-133)

Nephrocalcinosis/Nephrolithiasis3, n(%)

17 (81%)

35 (80%)

52 (80%)

Conventional therapy4

Elemental Calcium, mg/day, mean (SD)

1912 (2016)

1953 (2379)

1940 (2247)

Calcitriol, µg/day, mean (SD)

0.97 (0.86)

0.90 (0.45)

0.92 (0.60)

Alfacalcidol, µg/day, mean (SD)

2.06 (1.74)

2.82 (1.03)

2.62 (1.24)

43 unique CASR variants in study population

1Albumin-corrected serum calcium. 2eGFR for N=63 participants ≥18 years determined via CKD-EPI. Mean (range) eGFR for participants <18 years (n=4) was 85.8 (69-108) determined via Schwartz. 3Renal ultrasound performed at baseline in N=65 participants. Percentages are based on the number of participants with renal ultrasound available. 4Average doses over Period 1.

‌76% of participants randomized to encaleret achieved serum cCa1 and 24-hour urine calcium in the target ranges with restoration of iPTH secretion

(randomized to encaleret)

75.6%

91.1%

cCa 2.08-2.68 mmol/L

and

Normal 24hr UCa

1 Albumin-corrected serum calcium. 2Analyzed by McNemar's test.

‌Statistically significant changes in cCa1, 24-hour urine calcium and iPTH were also demonstrated in between-treatment comparisons

(encaleret vs. SoC2)

19.0%

75.6%

91.1%

1 Albumin-corrected serum calcium. 2Analyzed by Barnard's unconditional exact test.

‌Encaleret increased serum calcium and decreased urine calcium with changes maintained over 24 weeks

Mean difference of change from baseline

= 0.21 mmol/L (p<0.0001)*

Mean difference of change from baseline =

0.16 mmol/L (p=0.009)**

Mean difference of change from baseline

= - 5.01 mmol/day (p<0.0001)*

Mean difference

of change from baseline =

- 5.52 mmol/day (p<0.0001)**

1Albumin-corrected serum calcium. Data reported as mean±SD. Solid line for urine calcium reflects the upper limit for men and dashed line reflects upper limit for women.

*Within patient comparison of change from baseline of Week 4 vs Week 24. **Between group comparison of change from baseline of Period 3 Week 24.

‌Encaleret decreased serum phosphate and increased serum magnesium with changes maintained over 24 weeks

Mean difference of change from baseline

= - 0.25 mmol/L (p<0.0001)*

Mean difference of change from baseline =

- 0.18 mmol/L (p=0.004)**

Mean difference of change from baseline

= 0.09 mmol/L (p<0.0001)*

Mean difference

of change from baseline =

0.05 (p=0.002)**

1Albumin-corrected serum calcium. Data reported as mean±SD. Solid line for urine calcium reflects the upper limit for men and dashed line reflects upper limit for women.

*Within patient comparison of change from baseline of Week 4 vs Week 24. **Between group comparison of change from baseline of Period 3 Week 24.

‌Encaleret was well-tolerated with no TEAEs resulting in encaleret or study discontinuation

Period 1

Periods 2 and 3

SoC

N=67

SoC

N=22

Encaleret

N=45

TEAE Leading to Study Discontinuation

0 (0%)

Participants experiencing any Serious TEAE

2 (3%)

3 (14%)

4 (9%)

Serious Related TEAE

1 (2%)

0 (0%)

1 (2%)

Participants experiencing any TEAE

30 (45%)

14 (64%)

40 (89%)

Mild

23 (34%)

6 (27%)

21 (47%)

Moderate

4 (6%)

6 (27%)

16 (36%)

Severe

3 (5%)

2 (9%)

3 (7%)

Related TEAE

4 (6%)

0 (0%)

16 (36%)

TEAEs in ≥5% of participants by preferred term

Hypercalcemia

3 (4.5)

10 (22.2)

Headache

1 (4.5)

9 (20.0)

Constipation

2 (9.1)

5 (11.1)

Nausea

1 (1.5)

3 (13.6)

4 (8.9)

Fatigue

1 (4.5)

4 (8.9)

Hypertension

1 (4.5)

4 (8.9)

Hypocalcemia

4 (6.0)

3 (13.6)

3 (6.7)

Urinary tract infection

3 (4.5)

1 (4.5)

3 (6.7)

Sinusitis

2 (9.1)

2 (4.4)

For each category, participants are included only once, even if they experienced multiple events in that category. Relatedness assessed on the basis of the investigational product being administered in the respective study period reported.

TEAE = Treatment-Emergent Adverse Event

‌Summary

76% of participants with ADH1 randomized to encaleret achieved serum and urine calcium in the

target range

- Among encaleret responders at Week 24, none required conventional therapy during Period 3

91% of participants randomized to encaleret achieved restoration of endogenous iPTH

Encaleret was well-tolerated with no discontinuations related to study drug

In patients with ADH1, encaleret administered twice daily rapidly corrects and maintains mineral homeostasis within the normal range, as demonstrated by:

Increase in PTH

Correction of hypocalcemia

Normalization of mean 24-hr urine calcium

Reduction in mean serum phosphate

Increase in mean serum magnesium

Trial in pediatric patients with ADH1 is ongoing

BridgeBio

‌Acknowledgements

Thank you to the patients and their families, the study sites and support staff

BridgeBio

Disclaimer

BridgeBio Pharma Inc. published this content on May 12, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 12, 2026 at 10:05 UTC.