Clinical Thyroidology® for the Public

Summaries for the Public from recent articles in Clinical Thyroidology
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HYPOPARATHYROIDISM
TransCon PTH: a promising treatment for chronic hypoparathyroidism

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BACKGROUND
The parathyroid glands are usually 4 small, buttonshaped glands located next to the thyroid in the neck, 2 on each side. They have nothing to do with the thyroid; they are just located next to the thyroid. They produce parathyroid hormone (PTH), which helps regulate calcium and phosphate levels in the body. When calcium levels decrease, PTH is turned on and draws calcium from the bones, prevents calcium from going out in the urine, and activates Vitamin D to help absorb calcium from the gut, returning calcium levels to normal. When the parathyroid glands don’t make enough PTH, it leads to hypoparathyroidism—a condition marked by low calcium levels in the blood (hypocalcemia). Hypoparathyroidism can cause abnormal heart rhythms, weakened bones, kidney stones, and reduced kidney function. People may also experience symptoms such as muscle cramps, twitching, and difficulty thinking clearly. The most common cause of hypoparathyroidism is surgery, particularly surgery involving the thyroid or head and neck, where the parathyroid glands may be accidentally damaged or removed.

To maintain stable blood calcium levels, patients with hypoparathyroidism must take oral calcium supplements multiple times a day, along with a form of vitamin D called calcitriol. Despite this, calcium levels can fluctuate, requiring frequent blood tests and medication dose adjustment. The burden of managing these symptoms and treatment demands can also negatively impact one’s quality of life.

TransCon PTH (palopegteriperatide) is a new treatment for chronic hypoparathyroidism. This medication is a long-acting form of parathyroid hormone given as a daily injection under the skin. It maintains steady levels of PTH in the blood, directly addressing the hormonal deficiency rather than just treating the symptoms of low calcium. It should, in theory, remove the need for people with hypoparathyroidism to take calcium and vitamin D tablets.

The current study evaluated the effectiveness and safety of TransCon PTH in patients with chronic hypoparathyroidism

THE FULL ARTICLE TITLE
 Clarke BL, et al. Efficacy and safety of TransCon PTH in adults with hypoparathyroidism: 52-week results from the phase 3 PaTHway trial. J Clin Endocrinol Metab. Epub 2024 Oct 8.

SUMMARY OF THE STUDY
This was a Phase 3 clinical trial to evaluate the safety and effectiveness of TransCon PTH in individuals with chronic hypoparathyroidism, most of whom (85%) acquired the condition after head and neck surgery. Trials like this one must be conducted before a drug can be approved for use. During the first 26 weeks, 82 participants were randomly assigned to receive either TransCon PTH (61 individuals) or a placebo (21 individuals). The trial then entered an open-label phase where all participants received TransCon PTH for another 26 weeks, resulting in a total follow-up period of 52 weeks.

The primary aim was to determine whether participants could stop taking calcium and active vitamin D supplements while maintaining normal blood calcium levels. Other outcomes included patient satisfaction, overall quality of life, safety, and changes in bone mineral density. Too much PTH can decrease bone density by taking too much calcium out of the bones.

Out of the 82 people who started the study, 78 were still taking part after 52 weeks. Of those, 74 (or 95%) no longer needed to take calcium and vitamin D supplements. People taking TransCon PTH said they felt better quickly, with improvements in their quality of life and overall well-being. While bone density did not increase with the drug, it also didn’t get worse, apart from the slight decline that normally happens with age. About 53% of participants had side effects, but they were mild, and no one had to stop taking the medication because of them.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The authors conclude that TransCon PTH is a safe and effective treatment and could potentially have a positive impact on people living with chronic hypoparathyroidism, a condition that is very challenging to manage with current therapies.

— Phillip Segal, MD

ABBREVIATIONS & DEFINITIONS

Hypoparathyroidism: low calcium levels due to decreased secretion of parathyroid hormone (PTH) from the parathyroid glands next to the thyroid. This can occur as a result of damage to the glands during thyroid surgery and usually resolves. This may also occur as a result of autoimmune destruction of the glands, in which case it is usually permanent.

Parathyroid glands: usually four small glands located around the thyroid that secrete parathyroid hormone (PTH) which regulates the body’s calcium levels.

Parathyroid hormone (PTH): the hormone that regulates the body’s calcium levels. High levels of PTH cause hypercalcemia, or too much calcium in the blood. Low levels of PTH cause hypocalcemia, or too little calcium in the blood.

Clinical trials: when a new drug is developed, it must undergo an extensive series of steps, called phases, to prove that it is more effective in patients than the drugs that are currently available to treat the condition. A Phase 1 trial tests a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range and identify side effects. A Phase 2 trial gives the drug to a larger group of people to see if it is effective and to further evaluate its safety. A Phase 3 trial gives the drug to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments and collect information that will allow the drug or treatment to be used safely.

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