Dosing starts in clinical trial of MBX 2109, PTH replacement therapy
Patients who finished Phase 2 study may enter a long-term extension
Dosing is underway in a Phase 2 clinical trial of MBX 2109, an investigational hormone replacement therapy for people with hypoparathyroidism, according to the therapy’s developer, MBX Biosciences, with top-line expected around mid-2025.
The trial, called Avail (NCT06465108), is evaluating the safety, effectiveness, and pharmacological properties of MBX 2109 in about 48 adults with hypoparathyroidism. Eligible adult patients are being enrolled at 14 clinical sites across the U.S.
Details of the study, due to conclude in June, were presented at the 2024 American Society for Bone and Mineral Research (ASBMR) Annual Meeting, recently held in Toronto.
“We are pleased to share more information on our ongoing Phase 2 MBX 2109 trial in patients with [hypoparathyroidism] at ASBMR,” Kent Hawryluk, president and CEO of MBX, said in a company press release. “We believe this study will provide insight into its potential to provide patients with consistent and convenient relief from the burdensome symptoms caused by PTH [parathyroid hormone] deficiency and identify appropriate doses to be studied in the Phase 3 program.”
Replacement therapy gives patients a lab version of parathyroid hormone
Hypoparathyroidism is marked by PTH deficiency, resulting in abnormally low calcium and higher than normal phosphorus levels in the blood. Conventional treatment includes calcium and vitamin D supplements, which do not address the disease’s underlying cause.
Hormone replacement therapy, giving a patient a lab version of the parathyroid hormone, is another treatment option. This year, one such treatment called Yorvipath (palopegteriparatide) was approved in the U.S. for adults with hypoparathyroidism.
MBX 2109 is a lab-made, inactive form of PTH that is converted into its active form inside the body. The therapy is designed to be a long-acting hormone replacement therapy given once weekly to normalize blood calcium levels, reduce the need for supplements, and improve patient convenience and treatment adherence.
In the first part of a placebo-controlled Phase 1 clinical trial (NCT05158335), healthy adults received a single under-the-skin injection of one of five ascending doses of MBX 2109 (50, 150, 300, 460, or 600 micrograms, mcg) or a placebo. Results indicated the therapy was safe and well tolerated.
In its second and multiple-dose part, adults were given one of four therapy doses (200, 400, 600 or 900 mcg) or the placebo once weekly for four weeks.
Dose-dependent changes in blood calcium levels seen in Phase 1 study
Reported results showed a dose-related increase in mean albumin-adjusted blood calcium levels, and a dose-dependent suppression of endogenous (the body’s own) PTH hormone. Of note, albumin is the most abundant protein found in blood plasma.
In the Phase 2 Avail trial, participants undergo a four-week optimization period for the doses of calcium, vitamin D, and/or magnesium supplements to achieve normal calcium blood levels. They then are randomly assigned to a placebo or MBX 2109 at escalating three doses — 400, 600, or 800 mcg — administered as a weekly, subcutaneous (under-the-skin) injection for 12 weeks, or about three months.
Doses are fixed in the first four weeks, before being titrated (adjusted) over the subsequent eight weeks. During this period, doses of MBX 2109 and of active vitamin D and calcium supplements are adjusted to reduce the risk of low or high calcium levels.
The study’s main goal is to assess the proportion of patients who can completely stop vitamin D supplements and lower to 600 mg or less their calcium supplement dose at week 12, while maintaining normal blood albumin-adjusted calcium levels (8.2-10.6 mg/deciliter).
Additional goals include assessing MBX 2109’s safety and tolerability, as well as its pharmacokinetics (its movement into, through, and out of the body) and pharmacodynamics (its effects on the body). How MBX 2109 impacts patients’ quality of life also will be evaluated using patient-reported outcome tools.
Participants who complete the study’s 12-week treatment period may enroll in an open-label, long-term extension study (NCT06531941) of MBX 2109 given as a weekly injection. Those previously randomized to a placebo will be treated with MBX 2109 at a 400 mcg dose, while others will continue with MBX 2109 at their titrated dose in the main trial (ranging from 200 to 1600 mcg). This safety and tolerability study is expected to run for about two years (104 weeks).
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