Abaloparatide (BA058) is a synthetic analog of PTHrP134 which greatly increases bone mass and bone strength with preservation of normal bone quality in animal models of osteoporosis. Daily s.c. abaloparatide (ABLSC) at doses of up to 80 μg daily in postmenopausal women with osteoporosis for up to 48 weeks were associated with increases in spine and femoral neck BMD of up to 12.9 and 4.1% respectively and good safety and tolerability. The increases in BMD at the 80 μg dose exceeded those seen with teriparatide (Forteo) 20 μg s.c. daily (TER) in a head-to-head study. ABLSC is in a large phase three fracture study due to complete this year. Many, but not all, patients with osteoporosis can self-administer injections of TER or ABLSC, but a dosage form that increases BMD and avoids the need for injections would clearly be a valuable alternative for some patients.
Using 3Ms solid Microstructured Transdermal System (sMTS), which consists of an array of 316 microprojections that penetrate the skin to about 250 μm, through the stratum corneum into the upper dermis, we developed a short-wear-time abaloparatide transdermal (ABLTD) patch coated with doses of 50, 100 and 150 μg, and a placebo patch. 199 postmenopausal osteoporotic patients applied a patch containing either one of these three doses or placebo daily to their peri-umbilical skin for 5 min once daily for up to 24 weeks. At the end of treatment spine and hip BMD increased dose dependently, with 150 μg increasing these by 2.9% (P<0.001) and 1.5% (P=0.002) relative to placebo, respectively. Therefore, this study provides strong proof of concept that a transdermal patch delivering abaloparatide produces meaningful increases in spine and hip BMD. ABLTD was generally well tolerated. With further optimization, this approach holds substantial promise for a future alternative to existing and investigational injectable treatments for osteoporosis.
17 May 2014 - 20 May 2014