HONOLULU, Hawaii—The parathyroid hormone (PTH) analogue Ostabolin-Câ„¢ can be delivered by dry-powder inhaler at biologically active levels and might be a good replacement for current formulations that require subcutaneous injection, Paul Morley, PhD, reported at the American Society for Bone and Mineral Research (ASBMR) 2007 annual meeting^.1 Dr. Morley is chief scientific officer of Zelos Therapeutics, Inc, in Ontario, Canada, the company that is developing Ostabolin-C.

"Subcutaneous dosing of Ostabolin C has been shown to significantly increase bone mineral density (BMD). Ostabolin-C inhalation powder (OCIP) has potential for better therapeutic benefit and greater convenience," Dr. Morley said.

Ostabolin-C is a cyclic analogue of human parathyroid hormone (PTH) (1-31) that has demonstrated marked increases in BMD of the lumbar spine and hip.

This study of OCIP was carried out in 72 postmenopausal women aged 47 to 74 years in cohorts of eight (six active subjects, two placebo subjects) at escalating doses of OCIP. They were compared to outcomes in two cohorts using subcutaneous (SC) doses.

According the investigators, OCIP had pharmacokinetics similar to SC Ostabolin with either single or repeat dosing and had no evidence of accumulation. "Based on AUC (area-under-curve) and CMAX values, OCIP delivery is about 10% bioavailable relative to SC." Dose-dependent increases in urinary cyclic 3'5'-adenosine monophosphate (cAMP) also showed OCIP to have about 10% of the relative potency of SC dosing. The researchers also found that a 4% formulation of OCIP was more bioavailable and effective than a 16% formulation owing to more favorable aerosol characteristics.

Analysis of the therapeutic impact of OCIP on bone markers showed that

• OCIP increased bone formation markers
  
• OCIP did not change bone resorption markers
  
• OCIP increased 1,25-dihydroxyvitamin D

As expected, none of these changes were observed in the placebo-treated subjects.

Adverse events (AEs) were mostly mild and were those typically associated with PTH administration, such as headache, nausea, and a dose-dependent increase in heart rate. "There were no treatment-emergent pulmonary or cardiovascular AEs, no effect on pulmonary function, and no clinically relevant laboratory abnormalities," Dr. Morley reported. Tolerability was poor at doses of 1.2 mg or higher. Serial total serum calcium was affected only at the 1.2 mg dose.

Reference

1. Morley P, Bishop J, Anderson R, et al. Pulmonary delivery of the parathyroid hormone analogue Ostabolin-Câ„¢ stimulates markers of bone formation in postmenopausal women. Presented at: ASBMR 29th Annual Meeting; September 16, 2007; Honolulu, HI. Abstract S421.