Research That Changes Lives
We’re in a pivotal moment for treating non‑surgical genetic hypoparathyroidism and ADH1.
Treatment Landscape
The treatment landscape for non‑surgical genetic hypoparathyroidism and ADH1 is transforming. After decades of limited options that treat only symptoms, a new class of drugs — calcilytics — targets the underlying molecular mechanism.
Conventional Therapy
Current standard‑of‑care relies on calcium and active vitamin D supplements to manage symptoms. These do not address the underlying CaSR gain‑of‑function mutation and carry risks of long‑term complications including nephrocalcinosis.
Calcilytics
Calcilytics are negative allosteric modulators of the calcium‑sensing receptor (CaSR). By reducing the receptor’s over‑activity, they allow the body to restore normal calcium and PTH regulation — treating the cause, not just the symptoms.
Encaleret
Developed by BridgeBio Pharma (Calcilytix Therapeutics), encaleret is the most advanced calcilytic in clinical development for ADH1.
Phase 2b
Published in the New England Journal of Medicine (2023). 13 participants demonstrated rapid normalisation of blood calcium and PTH levels.
Phase 3 CALIBRATE
Top‑line results (October 2025): 76% achieved target calcium vs 4% placebo (p<0.0001). 91% restored PTH vs 7% (p<0.0001). 70 adults enrolled, 67 randomised 2:1. Well tolerated.
Regulatory Progress
NDA submission planned H1 2026. FDA Fast Track and Orphan Drug Designation granted (US, EU, Japan). Paediatric and chronic hypoparathyroidism studies planned 2026.
Australian Trial Site
Royal North Shore Hospital, St Leonards NSW (ANZCTR registered). Australian patients may be eligible for ongoing and future calcilytic clinical trials.
Encaleret: From Discovery to Approval
Tracking the journey of the first calcilytic therapy for ADH1 patients — from early research through to anticipated regulatory approval.
Preclinical Research
Calcilytix Therapeutics (now part of BridgeBio) identifies encaleret as a potent, selective CaSR negative allosteric modulator. Preclinical models demonstrate calcium and PTH normalisation.
CompletePhase 1 / Phase 2a
First-in-human studies confirm safety and demonstrate dose-dependent increases in calcium and PTH in ADH1 patients. Proof-of-concept established.
CompletePhase 2b — NEJM Publication
13 adults with ADH1 treated for 24 weeks. Rapid normalisation of blood calcium and PTH. Published in the New England Journal of Medicine (Roberts et al., 2023).
CompletePhase 3 CALIBRATE — Top-Line Results
70 adults enrolled, 67 randomised 2:1. 76% achieved target calcium vs 4% placebo (p<0.0001). 91% restored PTH vs 7%. Well tolerated with no safety signals.
CompleteNDA Submission (FDA)
New Drug Application filing planned with the US FDA. Encaleret holds FDA Fast Track designation and Orphan Drug status in the US, EU, and Japan.
In ProgressPaediatric & Chronic Hypopara Studies
Planned extensions to study encaleret in children with ADH1 and adults with chronic hypoparathyroidism (post-surgical and other causes).
PlannedAustralian TGA & PBS Access
Following US/EU approval, a TGA submission is anticipated for Australia. CaSR Patient Support will advocate for expedited evaluation and PBS listing to ensure affordable patient access.
PlannedCLARIFY Study
An ongoing 5‑year observational natural history study (NCT05227287) characterising disease burden in ADH1 patients across all age groups.
Paediatric Presentation
ADH1 frequently presents in childhood. Seizures occur in 39% of patients overall, and severely symptomatic patients present at significantly younger ages (Roszko et al., JBMR 2022; n=191).
Complication Rates
On conventional therapy, 38% develop nephrocalcinosis and 36% develop kidney stones. These data reinforce the urgent need for targeted therapies (Roszko et al., JBMR 2022; n=57).
How Drug Approval Works in Australia
New medicines must pass through a rigorous multi‑stage process before patients can access them on the Pharmaceutical Benefits Scheme.
TGA Evaluation
The Therapeutic Goods Administration evaluates safety, quality, and efficacy. The sponsor submits a dossier and the TGA assesses whether the medicine meets Australian standards.
ARTG Registration
Approved medicines are listed on the Australian Register of Therapeutic Goods. This permits lawful supply in Australia but does not guarantee affordability.
PBS Listing (PBAC)
The Pharmaceutical Benefits Advisory Committee assesses cost‑effectiveness. PBS listing makes the medicine affordable for patients through government subsidy.
Medical Advisory Board
Our Medical Advisory Board ensures that CaSR Patient Support’s advocacy is grounded in the best available evidence and clinical expertise.
Prof Roderick Clifton‑Bligh
Head of the Medical Advisory Board. Professor Clifton‑Bligh leads the board’s review of scientific positions and ensures our advocacy translates the latest evidence into meaningful action for patients.
Evidence‑Based Advocacy
The board reviews all clinical and scientific positions, translates complex research into accessible patient communications, and ensures our campaigns and policy submissions are rigorously evidence‑based.
