Delving into the Latest Updates on PTH Antagonist(Crinetics) with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

PTH1R

Mechanism

PTH1R agonists(Parathyroid hormone receptor agonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication

Hyperthyroidism

Inactive Indication-

Originator Organization

Crinetics Pharmaceuticals, Inc.

Active Organization

Crinetics Pharmaceuticals, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1–84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment.

Methods:

The study was a Phase III, open-label, non-comparative, clinical investigation (study period: 3 months), at a tertiary care clinical research center. Thirty patients with chronic hypoparathyroidism were screened, and 12 started teriparatide. After the optimization phase (0–4 weeks), calcium and calcitriol supplements were progressively reduced, while teriparatide 20 µg once daily was administered (5–7 weeks), and then could be titrated up to 20 µg twice daily (7–17 weeks). The main outcome measures included serum and urinary biochemical exams and Rand 36-Item Short Form Health Survey.

Results:

This study showed that teriparatide 20 µg once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal serum calcium concentrations. Conversely, for more than half of patients treated with teriparatide 20 µg twice daily, calcium and calcitriol administration was avoidable, but in some cases at the expense of serum calcium and phosphate oscillations.

Conclusions:

Since intervention trials evaluating the efficacy and safety of teriparatide in hypoparathyroid patients are not yet available, the routine use of this molecule poses some doubts.

01 Jun 2016·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

Management of Hypoparathyroidism: Present and Future

Q2 · MEDICINE

Review

Author: Liberman, Uri A. ; Mannstadt, Michael ; Rejnmark, Lars ; Potts, John T. ; Brandi, Maria Luisa ; Cusano, Natalie E. ; Bilezikian, John P. ; Winer, Karen K. ; Rubin, Mishaela R. ; Rizzoli, René

Abstract:

Context::

Conventional management of hypoparathyroidism has focused upon maintaining the serum calcium with oral calcium and active vitamin D, often requiring high doses and giving rise to concerns about long-term consequences including renal and brain calcifications. Replacement therapy with PTH has recently become available. This paper summarizes the results of the findings and recommendations of the Working Group on Management of Hypoparathyroidism.

Evidence Acquisition::

Contributing authors reviewed the literature regarding physiology, pathophysiology, and nutritional aspects of hypoparathyroidism, management of acute hypocalcemia, clinical aspects of chronic management, and replacement therapy of hypoparathyroidism with PTH peptides. PubMed and other literature search engines were utilized.

Evidence synthesis::

Under normal circumstances, interactions between PTH and active vitamin D along with the dynamics of calcium and phosphorus absorption, renal tubular handing of those ions, and skeletal responsiveness help to maintain calcium homeostasis and skeletal health. In the absence of PTH, the gastrointestinal tract, kidneys, and skeleton are all affected, leading to hypocalcemia, hyperphosphatemia, reduced bone remodeling, and an inability to conserve filtered calcium. Acute hypocalcemia can be a medical emergency presenting with neuromuscular irritability. The recent availability of recombinant human PTH (1–84) has given hope that management of hypoparathyroidism with the missing hormone in this disorder will provide better control and reduced needs for calcium and vitamin D.

Conclusions::

Hypoparathyroidism is associated with abnormal calcium and skeletal homeostasis. Control with calcium and active vitamin D can be a challenge. The availability of PTH (1–84) replacement therapy may usher new opportunities for better control with reduced supplementation requirements.

15 Aug 2011·TransplantationQ2 · MEDICINE

Teriparatide Efficacy in the Treatment of Severe Hypocalcemia After Kidney Transplantation in Parathyroidectomized Patients: A Series of Five Case Reports

Q2 · MEDICINE

Article

Author: Santana, Alice ; Costa, Antonio G. ; Costa, Ana C. ; Mil-Homens, Clara ; Guerra, Jose O. ; Silva, Sonia ; Nogueira, Estela L.

BACKGROUND:

Teriparatide is a recombinant human parathormone (PTH 1-34) currently approved for the treatment of osteoporosis with high risk of fracture. In this study, we analyze the efficacy and safety profile of teriparatide therapy in severe and prolonged hypocalcemia after kidney transplantation in patients previously submitted to parathyroidectomy.

METHODS:

The authors report results from a series of five hemodialyzed patients (mean age: 50±15 years; three female) previously submitted to parathyroidectomy to control secondary hyperparathyroidism. All patients had developed severe refractory hypocalcemia (calcium minimum levels: 5±1.4 mg/dL) early after kidney transplantation. The effect of teriparatide in calcemia and phosphatemia levels was analyzed, and variations in calcium and vitamin D analog requirements were analyzed. Secondary effects and serum creatinine changes were also ascertained.

RESULTS:

Teriparatide therapy was initiated 32±14 days after the development of hypocalcemia. As a result, calcemia levels increased (median±standard deviation [SD]: 6.7±0.8 vs. 8.5±0.8 mg/dL, P=0.024) allowing suspension of intravenous calcium in two patients and reduction of calcitriol doses (mean±SD: 1.1±0.38 vs. 0.55±0.27 μg/day, P=0.004). In addition, phosphatemia levels (median±SD: 5.1±1.5 vs. 3.9±0.5 mg/dL, P=0.09) and calcium carbonate requirements (mean±SD: 13.8±9.4 vs. 7.2 ±3.7 g/day, P=0.9) exhibited declining trends. No secondary effects were observed and creatinemia remained stable.

CONCLUSIONS:

Our data strongly suggest that refractory hypocalcemia after kidney transplantation in patients with low PTH levels can be successfully treated with teriparatide. PTH analog therapy leads to faster normalization of calcemia, permits earlier suspension of intravenous calcium supplementation, and reduces calcitriol requirements.

100 Deals associated with PTH Antagonist(Crinetics)

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