Entera Bio’s investigational parathyroid hormone compound called Oral PTH (1-34) appears to be able to increase calcium levels in patients with hypoparathyroidism, interim results from a Phase 2 trial show.
It can also increase blood levels of active vitamin D and reduce phosphate levels — two other hallmarks of this condition.
“The results from Part 1 of the pharmacokinetic and pharmacodynamic study in patients with hypoparathyroidism have confirmed that Oral PTH (1-34) activates biological pathways that parathyroid hormone is known to regulate,” Phillip Schwartz, PhD, CEO of Entera Bio, said in a press release.
Pharmacokinetics studies the movement of a compound into, through, and out of the body — essentially how the body affects a medicine, while pharmacodynamics are the interactions between the body and a compound.
“This study builds on and supports our previous PK [pharmacokinetic] results in more than 100 subjects and confirms that Oral PTH (1-34) is effectively delivered into the blood stream,” he added.
Hypoparathyroidism is characterized by the body’s inability to produce sufficient amounts of the parathyroid hormone. This rare condition often manifests by abnormally low levels of calcium and high levels of phosphate in the blood.
In 2015, the U.S. Food and Drug Administration approved Shire’s injectable parathyroid hormone therapy, Natpara, which became the first available treatment to manage hypoparathyroidism. In 2017, the treatment was made available in Europe under the brand name Natpar.
Although patients have these injectable treatment options to manage their disease, an oral formulation of parathyroid hormone would hold significant advantages. In addition, studies have suggested that multiple doses are more efficient in managing hypoparathyroidism symptoms.
The Phase 2 trial (NCT03516773), which is being conducted in Israel, was designed to evaluate the overall distribution, stability, and biological impact of Oral PTH (1-34) compared with Natpara. The study is still recruiting.
In the first part of this partial crossover study, 10 patients completed two three-day in-patient visits, during which they continued to receive their current standard medications.
On the first day of each visit, patients received no additional treatments. On the second day, they were randomly divided into three groups to receive either Oral PTH (1-34) twice a day, four times a day, or injectable Natpara once a day. On the last day, the patients did not receive any additional treatments.
Upon completion of this evaluation, the three-day visit protocol was repeated, and by the second day, patients were again randomized to receive one of the treatment regimens they had not gotten previously.
During the two three-day periods, blood samples were collected to measure levels of parathyroid hormone, calcium, phosphate, and active vitamin D. Urine samples were also collected to measure 24-hour urinary calcium changes.
Initial data analysis revealed that Oral PTH (1-34) supported a sustained increase in blood calcium levels by an average of approximately 0.3 mg/dL over the initial amounts over a 24-hour period.
In addition, the levels of phosphate decreased an average of 0.5 mg/dL, a reduction that was also maintained over 24 hours. Patients also experienced about a 90% increase of blood active vitamin D, while levels of 24-hour urinary calcium decreased about 30% on the day of treatment from initial levels.
“These results further support our belief that the administration of Oral PTH (1-34) multiple times per day may improve hypercalciuria [high calcium levels] in hypoparathyroid patients,” Schwartz said.
A preliminary assessment revealed that taking the treatment four times per day could have a greater effect on all disease-associated parameters measured than the twice-daily regimen.
No serious adverse events were reported during the study, and Oral PTH (1-34)-induced levels of parathyroid hormone did not increase the levels of calcium to values that could represent potential damage.
In the second part, the trial will assess the impact of the treatment taken three times per day with a high and low dose of Oral PTH (1-34) compared with Natpara. Results are expected to provide further insights on the design of future clinical trials.
“Oral PTH (1-34) may offer significant advantages in hypoparathyroid patients to better manage their chronic disease, from both a compliance and efficacy perspective,” Schwartz said. “In Part 2 of this Phase 2 study, we look forward to collecting additional data on the treatment of hypoparathyroid patients, which will help support the advancement of Oral PTH (1-34) into a Phase 2b/3 study in which the clinical relevance of Oral PTH (1-34) would be evaluated.”
Complete results of the trial are expected to be presented in upcoming scientific meetings and published in peer-reviewed journals in 2019.