Who is affected?Hypoparathyroidism predominantly affects women but can also affect men. There are approximately 80,000 and 110,000 people with hypoparathyroidism in the U.S.1,2,3 and E.U., respectively, of which about 80% are women. More than two-thirds of women with hypoparathyroidism are peri- and menopausal women who are at an increased risk of developing osteoporosis, a condition characterized by weak and brittle bones that increases the risk of bone fractures. It is estimated that about 25% of people with hypoparathyroidism have chronic kidney disease or kidney failure.
What are the symptoms?Clinical manifestations of hypoparathyroidism vary and impact a large number of tissues and organ systems, including the muscles, brain, heart, and kidneys. Despite available treatments, patients frequently experience persistent, life-altering symptoms and reduced quality of life. In addition, they often develop kidney disease and have abnormal bone architecture.
Limitations of current treatmentsConventional therapies for patients with hypoparathyroidism include calcium supplements and activated vitamin D. These therapies do not adequately control symptoms, and long-term treatment with these therapies may result in dangerously high levels of calcium in the urine that can cause kidney stones, chronic kidney disease and impaired kidney function.2
Recombinant human PTH (1-84) is a once daily injection approved for adult patients with hypoparathyroidism who do not respond to conventional therapies. Replacing the missing or deficient PTH hormone is a more physiologic approach to treatment than conventional therapies, but because of its short half-life, rhPTH (1-84) doesn’t adequately regulate levels of calcium in the body for a full 24 hours, resulting in poor symptom control, and continued long-term risk to the kidneys. Consequently, patients continue to experience symptoms with no improvement in their reduced quality of life. Ongoing studies are further evaluating the safety of long-term use of PTH (1-84).2,5,6
More effective therapies that adequately control symptoms for a full 24 hours and that avoid unwanted side effects are urgently needed to restore balance for patients with hypoparathyroidism and enable them to live a normal life.
- Rao S. “Epidemiology of parathyroid disorders.” Best Pract Res Clin Endocrinol Metab. 2018 Dec;32(6):773-780.
- Powers J, et al. “Prevalence and incidence of hypoparathyroidism in the United States using a large claims data- base.” J Bone Miner Res. 2013;28:2570 –2576.
- Gafni R, et al. Hypoparathyroidism. New England Journal of Medicine. 2019.
- Rubin MR, et al. “Therapy of hypoparathyroidism with PTH(1-84): A prospective six year investigation of efficacy and safety.” J Clin Endocrinol Metab. 2016 Jul;101:2742-50.
- Mannstadt M, et al. “Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised phase 3 study.” Lancet Diabetes Endocrinol. 2013; 1: 275-83.
Lipodystrophy is an ultra-rare, life-threatening metabolic syndrome, characterized by either a complete or partial loss of fat tissue, that results in the absence of or the inability to respond to the hormone, leptin.
Lipodystrophy may be either inherited or acquired as a result of medications, radiation treatment, immune dysfunction or for unknown reasons. reasons. No cure currently exists for lipodystrophy.7,8
Patients with partial lipodystrophy lose subcutaneous fat (fat just under the skin), especially in the arms and legs, but accumulate fat around the neck, face and abdominal organs. This results in metabolic complications, including the development of diabetes, decreased levels of high density lipoprotein (HDL) cholesterol that protects against heart disease, and elevated triglycerides that can cause pancreatitis and hardening of blood vessels.9, 10 Partial lipodystrophy affects roughly 1,800 patients in the U.S. and E.U.11, and has no approved therapy in the U.S. due to poor efficacy and safety issues. There is one treatment approved for use in the E.U., but it is poorly effective.
Patients with general lipodystrophy have a complete absence of fat, resulting in severe metabolic complications including the development of diabetes, liver failure and elevated triglycerides.11 Although rare, general lipodystrophy affects roughly 700 patients in the U.S. and E.U., and it carries an extreme healthcare cost burden.12
Some available therapies treat specific symptoms of the disease, but fail to target the underlying cause. These same treatments are inefficient in severe forms, and are often associated with unwanted side effects. There is only one FDA-approved treatment for generalized lipodystrophy, but its use carries warnings for the risk of developing certain cancers (lymphomas) or antibodies that may prevent the treatment from working.
Given that no cure exists and conventional treatments fail to re-establish metabolic regulation, safe and effective therapies are greatly needed to treat metabolic complications in patients suffering from this severe disease.
- Garg A. “Lipodystrophies.” Am J Med 2000;108:143-152.
- Garg, A. “Acquired and inherited lipodystrophies.” N Engl J Med 2004;350:1220-1234.
- Bi, et al. “Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.” J Bone Miner Res. 2016 May;31(5):975-84.
- Garg A, et al. “Adipose tissue distribution in patients with familial partial lipodystrophy (Dunnigan variety).” J Clin Endocrinol Metab. 1999;84:170-174.
- Chiquette, E, et al. “Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges.” Diabetes Metab Syndr Obes. 2017; 10: 375–383.