CHICAGO — A nasal spray formulation of the osteoporosis drug, teriparatide, has cleared its first scientific hurdle.
Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.
Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of teriparatide nasal spray on 4 subsequent days. Two nasal formulations at two dose levels were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg and formulation No. 2 at 500 mcg and 1,000 mcg. Blood samples were collected up to 4 hours post treatment.
The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.
While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.
Still, while the bioavailability of Forteo was 95%, the bioavailability of the nasal formulation No. 1 was only about 5%–8% and 12%–15% for the second formulation.
Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing. “I think the take-home is that contrary to what you might think, the nasal spray in fact doesn't result in markedly greater variability than an injection,” he said.
There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia following any nasal spray dosing.
Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced. In a separate poster at the same meeting, cost and side effects were identified as significant barriers for patients considering teriparatide.
In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.
Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.
Of the 52 patients who responded to a survey about side effects, 26 reported one or more.