Hypoparathyroidism is defined by a deficiency of parathyroid hormone (PTH). PTH is produced by four small parathyroid glands that are located on the thyroid. A deficiency or absence of PTH results in decreased calcium and elevated phosphorus levels in the blood4, which are the primary laboratory findings of hypoparathyroidism. Loss of PTH most commonly occurs due to damage or removal of the parathyroid glands during thyroid or neck surgery.
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 treatments
Conventional 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
People living with hypoparathyroidism represent a heterogenous population with different clinical needs.
Controlling symptoms for a full 24 hours is paramount and more effective therapies to maintain serum calcium in the normal range are urgently needed to restore balance and enable patients with hypoparathyroidism to live a normal life.
Decreasing urinary calcium excretion and preventing kidney stones and long-term kidney disease are other key therapeutic goals as there is a 5-fold increase in the risk of long-term kidney complications and 26%7 of patients with hypoparathyroidism have already developed chronic kidney disease.
More than 50%8 of patients with hypoparathyroidism are peri- and post-menopausal women at an increased risk of developing osteoporosis and 17%7 actually have low bone mineral density (osteopenia or osteoporosis). In these patients, it is important to maintain bone integrity and, ideally, restore a more physiological bone turnover without inducing further demineralization of the bone.
- 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.
- Proprietary quantitative Market Research, 2021
- Proprietary retrospective Natural History Study, 2020
Acromegaly is a rare endocrine disorder, typically caused by a benign tumor of the pituitary gland that produces excessive growth hormone (GH), which in turn causes abnormally elevated levels of insulin-like growth factor-1 (IGF-1).
Who is affected?
The mean age of acromegaly diagnosis is 40-45 years, but it is often diagnosed 4-10 years after onset due to its slow progression. It is estimated that there are 26,000 acromegaly patients in the U.S.8 and an additional 35,000 in the E.U.
What are the symptoms?
Symptoms vary and depend on the age of onset. When acromegaly occurs after puberty, it is characterized by enlargement of the soft tissues. In the very rare instances when the disease occurs prior to puberty, the excess GH and IGF1 also cause abnormally accelerated growth that can result in gigantism. In both instances, common features include enlargement of the hands, feet and jaw. Medical complications include cardiovascular disease (such as hypertension, which occurs in 30-50% of patients9 and cardiomyopathy potentially leading to heart failure10), impaired glucose tolerance and diabetes mellitus (30%-50% of patients at diagnosis)9, hypogonadism (~50% of patients resulting from tumor mass effect)9, bone and joint diseases (including vertebral fractures reported in 60% of patients)9, cerebrovascular events, sleep apnea (80% of newly diagnosed patients)11 and impaired respiratory function11.
Limitations of current treatments
The current treatment paradigm includes surgery to remove the tumor, which may be curative, and which can normalize GH production and IGF-1 levels, but it is unsuccessful in ~60% of cases.
Medical therapies are also available to decrease the elevated IGF-1 levels caused by the excess GH produced in acromegaly. Somatostatin analogs (SSAs), which act directly on the pituitary to inhibit the secretion of GH, are often used first line. Dopamine agonists, which also suppress GH secretion from the pituitary, may be used as adjunct therapy. GH receptor antagonists, which act to block the interaction between GH and its receptor, are usually a second line monotherapy. Even with recent advancements, only about 40% of acromegaly patients achieve ideal symptom control using existing treatments.
Patients with persistent disease after surgery who are not adequately controlled with current medical therapy may undergo radiotherapy to suppress the pituitary tumor, but this option can be associated with significant additional morbidities and is not widely used.
As a result of the current treatment landscape, significant unmet needs persist for patients with acromegaly, in particular in terms of improved symptom control and long-term outcomes.
- Lavrentaki A, et al. “Epidemiology of acromegaly: review of population studies.” Pituitary. 2017; 20(1): 4-9. doi:10.1007/s11102-016-0754-x
- Burton T, et al. “Incidence and prevalence of acromegaly in a large US health plan database.” Pituitary. 2016; 19: 262-267. doi:10.1007/s11102-015-0701-2
- Giustina A, et al. “A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update.” J. Clin. Edocrinol. Metab. 2020; 105(4): dgz096. doi:10.1210/clinem/dgz096
- Colao A, et al. “Acromegaly and Heart Failure.” Heart Failure Clinics. 2019; 15(3): 399-408. doi: 10.1016/j.hfc.2019.03.001
- Adelman, DT et al. “Acromegaly: the disease, its impact on patients, and managing the burden of long-term treatment.” Int. J. Gen. Med. 2013;6:31-8. doi:10.2147/IJGM.S38594