TY - JOUR
T1 - Oral daily PTH(1-34) tablets (EB613) in postmenopausal women with low BMD or osteoporosis
T2 - a randomized, placebo-controlled, 6-month, phase 2 study
AU - Tripto-Shkolnik, Liana
AU - Szalat, Auryan
AU - Tsvetov, Gloria
AU - Rouach, Vanessa
AU - Sternberg, Chana
AU - Hoppe, Anke
AU - Burshtein, Gregory
AU - Galitzer, Hillel
AU - Toledano, Miranda
AU - Harari, Gil
AU - Santora, Arthur C.
AU - Cosman, Felicia
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6
Y1 - 2024/6
N2 - Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.
AB - Anabolic treatment is indicated for high and very-high risk patients with osteoporosis, but acceptance is limited because current anabolic medications require subcutaneous injections. The purpose of this study was to assess the effects of a novel orally administered PTH tablet on serum markers of bone formation (PINP and osteocalcin), bone resorption (crosslinked C-telopeptide [CTX]), BMD, and safety in postmenopausal women with low BMD or osteoporosis. In this 6-mo, double-blind, placebo-controlled study, 161 patients were randomized to oral PTH tablets containing 0.5, 1.0, 1.5, or 2.5 mg or placebo daily. Biochemical markers were assessed at 1, 2, 3, and 6 mo and BMD of LS, TH, and FN was measured at 6 mo. Biochemical marker changes were dose dependent with minimal or no effect at the 2 lowest doses. At the highest dose (2.5 mg once daily), serum PINP and OC levels increased 30% within 1 mo after oral PTH initiation (P < .0001), remained elevated through 3 mo, and were back to baseline at 6 mo. In contrast, serum CTX levels declined 16% and 21% below baseline at 3 and 6 mo, respectively (both P ≤ .02). At 6 mo, 2.5 mg tablets increased mean BMD vs placebo of the LS by 2.7%, TH by 1.8%, and FN by 2.8% (all P ≤ .01). There were no drug-related serious adverse events. The most common adverse events were headache, nausea, and dizziness. In contrast to subcutaneous PTH, the oral PTH tablet appears to increase BMD rapidly by the dual mechanism of stimulating formation and inhibiting bone resorption. This might be the first effective oral anabolic alternative to subcutaneous administration for the treatment of low BMD or osteoporosis.
KW - EBP05/EB613
KW - Entera Bio
KW - oral hPTH(1-34)
KW - oral PTH
KW - oral teriparatide
KW - osteoanabolics
KW - osteoporosis treatment
UR - http://www.scopus.com/inward/record.url?scp=85194374500&partnerID=8YFLogxK
U2 - 10.1093/jbmr/zjae057
DO - 10.1093/jbmr/zjae057
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C2 - 38578978
AN - SCOPUS:85194374500
SN - 0884-0431
VL - 39
SP - 672
EP - 682
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 6
ER -