Patients
About Hypoparathyroidism
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 blood1, 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.2,3,4 and E.U., respectively, of which about 80% are women.
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.
What are the complications?
More than two-thirds of women with hypoparathyroidism are peri- and post-menopausal and are, therefore, at an increased risk of developing osteoporosis, a condition characterized by weak and brittle bones that increases the risk of bone fractures. In addition, it is estimated that >50% of patients have elevated urinary calcium levels and about 25% of people with hypoparathyroidism have chronic kidney disease or kidney failure.
Limitations of current treatments
Despite conventional treatments, including calcium supplements and activated vitamin D, patients with hypoparathyroidism experience life-altering symptoms and often develop kidney and bone disease.
Unmet need
Standard of care treatments often do not keep calcium levels in the blood stable for a long period of time, which leads to frequent and severe symptoms.
They do not decrease urinary calcium, putting patients at risk of kidney disease. There is a 5-fold increase in the risk of long-term kidney complications and 26%5 of patients with hypoparathyroidism have already developed chronic kidney disease.
More than 50%6 of patients with hypoparathyroidism are peri- and post-menopausal women at an increased risk of developing osteoporosis and 17%5 actually have low bone mineral density (osteopenia or osteoporosis). Hypoparathyroidism causes abnormally low levels of bone turnover resulting in areas of bone thickening with abnormal structure likely to reduce elasticity and resistance to mechanical stress. Calcium supplementation and active vitamin D do not address this abnormality in bone metabolism leaving patients vulnerable to the risk of fractures over time.
Patient Stories:
Resources and Support:
- https://rarediseases.org/rare-diseases/hypoparathyroidism/
- Gafni R, et al. Hypoparathyroidism. New England Journal of Medicine. 2019.
- 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.
- Proprietary quantitative Market Research, 2021
- Proprietary retrospective Natural History Study, 2020
ABOUT ACROMEGALY
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.7 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 patients8 and cardiomyopathy potentially leading to heart failure9), impaired glucose tolerance and diabetes mellitus (30%-50% of patients at diagnosis)8, hypogonadism (~50% of patients resulting from tumor mass effect)8, bone and joint diseases (including vertebral fractures reported in 60% of patients)8, cerebrovascular events, sleep apnea (80% of newly diagnosed patients)10 and impaired respiratory function10.
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 or not feasible 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.
Unmet need
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.
- 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
About Primary Hyperparathyroidism (PHPT)
PHPT results from excess parathyroid hormone (PTH) production due to enlargement, usually noncancerous, of one or more of the parathyroid glands. The parathyroid glands are located at the front base of the neck. Too much PTH results in an abnormally high level of calcium in the body. This is referred to as ‘hypercalcemia.’
Who is affected?
PHPT often affects people over 60 years of age, and it is more common in women. It is estimated that PHPT affects ~223/100,000 women and 85/100,000 men.
What are the symptoms?
Too much calcium in the blood affects the bones, gastrointestinal tract, kidneys, muscles, heart and brain. The most common symptoms of PHPT are fatigue, body aches, bone pain, depression, and headaches.
What are the complications?
Since PHPT can lead to weakening of the bones, the most common complication is osteoporosis. This increases a person’s likelihood of bone fracture.
Limitations of current treatments
PHPT is most commonly treated by surgery to remove the affected parathyroid gland. Failing cure from surgery, medical treatments focus on lessening the impact of hypercalcemia, but none directly address the overstimulation of the PTHR1.
Unmet need
There is a significant need for a medical therapy that can stop the overstimulation of the parathyroid hormone receptor 1 (PTHR1) and, in turn, eliminate the debilitating symptoms and complications associated with PTPH.
ABOUT HUMORAL HYPERCALCEMIA OF MALIGNANY (HHM)
HHM is the elevation of calcium in the blood, also known as ‘hypercalcemia,’ caused by excessive secretion of parathyroid hormone-related peptide (PTHrP) from tumor cells.
Who is affected?
Approximately 20% of all cancer patients develop hypercalcemia during their clinical course, and 80% of those cases are caused by excessive secretion of PTHrP from the tumor cells. Squamous cell carcinomas of the head, neck, esophagus and lung, and cancers of the cervix, lung and colon are most commonly involved, in addition to renal cell, bladder, breast, endometrial, and ovarian cancers. Based on a prevalence study 11 in the United States, HHM represented about 71,700 cases in 2013.
What are the symptoms?
HHM is associated with a wide spectrum of symptoms including nausea, vomiting, anorexia, abdominal pain, constipation, polyuria, hypotension, bone pain, bone loss, fatigue and confusion.
What are the complications?
Renal failure or coma can occur; thus, this condition may be considered an oncologic emergency. Longer-term, HHM results in osteoporosis, increasing a person’s likelihood of bone fracture.
Limitations of current treatments
Current standard of care is focused on anti-resorptive therapy to decrease calcium release from the bone, and intravenous hydration to enhance urinary calcium excretion. However there are many limitations to available therapy and unwanted side effects include fever, bone pain, kidney disease, too little calcium in the blood and damage to the jaw bones.
Unmet need
A better tolerated therapy that directly targets the interaction between PTHrP and the PTHR1, rather than the downstream effects on calcium release from bone and the reabsorption of calcium from urine in the kidney may provide a safer, more effective alternative.
- Gastanaga, Victor M et al. “Prevalence of hypercalcemia among cancer patients in the United States.” Cancer medicine vol. 5,8 (2016): 2091-100. doi:10.1002/cam4.749
Compassionate Use Policy
Amolyt Pharma is dedicated to providing physicians with new therapeutic strategies to improve the lives of their patients with rare endocrine and related diseases. Our goal is to bring safe and effective medicines to as many patients as possible by conducting rigorous clinical trials and obtaining marketing approval by regulatory authorities around the world. We are committed to the highest standards of preclinical and clinical research, and our work is driven by an acute sense of urgency. As such, we prioritize access to our investigational medicines through participation in a clinical trial.
Amolyt Pharma works collaboratively with health authorities to perform clinical trials for rare endocrine and related diseases and bring impactful medicines to patients as quickly as possible. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to eneboparatide, an investigational drug under clinical development for the treatment of chronic hypoparathyroidism (cHP).
At this time, Amolyt Pharma has not established an Expanded Access Program that allows patients access to eneboparatide outside of clinical trials or prior to regulatory approval. Amolyt Pharma recognizes the importance of Expanded Access Programs and may update this policy based on data from ongoing drug development programs and future clinical trials.