ECTS2013 Poster Presentations Osteoporosis: treatment (64 abstracts)
Transdermal delivery of BA058, a novel analog of hPTHrP (1-34), with a short wear time patch in preclinical and clinical studies
Gary Hattersley 1 , Kris Hansen 2 , Amy Determan 2 , Ken Brown 2 , Kate Mckay 1 , Jonathan Guerriero 1 , Dan McCarthy 1 , C Richard Lyttle 1 & Louis St L O’Dea 1
1Radius, Cambridge, Massachusetts, USA; 23M Drug Delivery Systems, St Paul, Minnesota, USA.
BA058 is being developed as an anabolic therapy for the treatment of osteoporosis. Daily BA058 SC injection has produced promising safety and efficacy results in early clinical studies, and is currently enrolling in a Phase 3 fracture prevention study. There is, however, a significant need for an alternative to injection that improves patient convenience and compliance. We have investigated the use of a solid Microstructured Transdermal System (3M) for transdermal (TD) delivery of BA058. The pharmacokinetics of BA058 TD were similar in both rats and monkeys, with an early Tmax, short T1/2, and a Cmax comparable to SC injection. Efficacy of BA058 TD was evaluated in OVX rats. Following a bone depletion period, rats were treated daily for 14-days with BA058 TD or BA058 SC. Femur BMD was increased (+4.8%) with BA058 TD, similar to the increase with BA058 SC (+4.2%). Trabecular bone microstructure were also improved in the femur metaphysis. Three Phase 1 clinical studies were also conducted to determine the PK, safety and tolerability of transdermal BA058 in post-menopausal women. Periumbilical application of BA058 TD (100, 150 and 200 mcg) resulted in a desirable PK profile, with rapid delivery, early peak concentration, fast elimination of BA058, and a Cmax that matched or exceeded SC injection (80 mcg). BA058 patch wear times up to 24 h were evaluated, with a 5-minute wear time optimal for complete BA058 delivery; wear times longer than 5-minutes resulted in no further BA058 release. Seven consecutive days of BA058 TD resulted in a marked increase in serum P1NP, consistent with retention of pharmacological activity and bone anabolism. After more than 300 patch applications to more than 100 subjects, BA058 TD demonstrated a favorable safety profile. Transdermal BA058 delivery using a short wear time patch potentially represents a new approach for osteoporosis treatment.
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Bone Abstracts
ISSN 2052-1219 (online)
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