Two clinical studies were conducted to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and potential immunogenicity of single and multiple escalating doses ( IV [ intravenous ] and SC [ subcutaneous ] ) of Blosozumab in postmenopausal women, including prior/current Alendronate users.
These phase 1 studies were subject- and investigator-blind, placebo-controlled, randomized studies evaluating escalating doses of Blosozumab: single IV doses up to 750 mg, single SC dose of 150mg, multiple IV doses up to 750mg every 2 weeks ( Q2W ) and multiple subcutaneous doses up to 270mg Q2W.
Up to 8 subjects were randomized to each dose in the single dose study and up to 12 subjects to each dose in the multiple dose study.
Safety parameters, including adverse events, and pharmacodynamic effects, including bone mineral density ( BMD ) and immunogenicity, were assessed for up to 12 weeks after the final dose of Blosozumab.
Blosozumab was well tolerated with no safety concerns identified following single or multiple administrations up to 750mg. Clinically and statistically significant bone biomarker responses were observed in sclerostin, procollagen-1 N-terminal peptide ( P1NP ), bone specific alkaline phosphatase ( BSAP ), osteocalcin ( OC ), and carboxyterminal cross-linking telopeptide of collagen type 1 ( CTx ).
A clinically and statistically significant anabolic response on bone was demonstrated through BMD following single and multiple ( up to 5 ) administrations of Blosozumab.
There was up to a 3.41% and up to a 7.71% change from baseline in lumbar spine BMD at day 85 following a single or multiple administration of Blosozumab, respectively.
The effects generally showed dose-related effects over the dose range tested and prior Alendronate use did not appear to have a major impact.
Antibodies to Blosozumab were detected but there was no pattern with regards to dose or route of administration and no suggestion of a neutralizing effect in terms of pharmacokinetics or pharmacodynamics parameters.
In conclusion, Blosozumab was well tolerated and exhibited anabolic effects on bone in these studies. These data support further investigation of blosozumab as a potential anabolic therapy for osteoporosis. ( Xagena )
Source: ASBMR Annual Meeting, 2012