Bone Density

November 2, 2015

Radius Health has issued results of a phase III trial of abaloparatide (ABL) subcutaneous (SC) injection for major osteoporotic fractures in women with postmenopausal osteoporosis (PMO). ACTIVE is a randomized, double-blind, placebo-controlled trial evaluating fracture prevention in more than 2,400 women. Women were randomized to receive 18 months of either daily ABL 80mcg SC, matching placebo SC, or open-label teriparatide (TPTD) 20mcg SC. Compared with placebo-treated subjects, ABL-SC-treated subjects had a 70% reduction in major osteoporotic fractures (HR=0.30, 95% CI: 0.15, 0.61; p=0.0004), which also was 55% lower compared to TPTD (HR=0.45, 95% CI: 0.21, 0.95; p=0.031). Compared to placebo, TPTD-treated subjects did not achieve a statistically significant reduction in clinical, non-vertebral or major osteoporotic fractures. A further analysis of the ACTIVE trial showed greater response rates for BMD at three combined anatomical sites (total hip, femoral neck and lumbar spine) in PMO women treated with ABL-SC for 18 months when compared to placebo or TPTD at six, 12 and 18 months.

October 27, 2014

Repros Therapeutics reported results of a phase III study of Androxal (ZA-303) to evaluate the effects on bone mineral density of administration of Androxal for 52 weeks to overweight men with acquired hypogonadotropic hypogonadism. The study enrolled 317 men younger than 60 years old with BMI greater than 25 if they had morning testosterone of <300ng/dL on two screening visits. The single-blind, placebo-controlled, multi-center study initiated dosing at 12.5mg and dose escalated as necessary to 25mg. Of enrolled subjects, 213 and 104 subjects were treated with Androxal and placebo, respectively. The study results showed no evidence of a negative effect on bone mineral density in subjects treated with Androxal in comparison to the placebo treatment group. However, placebo-treated subjects experienced a statistically significant decrease from baseline in Total Hip bone mineral density (-0.63%) than subjects treated with Androxal (0.01%, p = 0.0043). The percentage of Androxal-treated subjects obtaining a morning testosterone over 300ng/dL in a 12-month treatment window was 79.3%, and 71.4% had a normal testosterone at their last observation on treatment. Androxal was well-tolerated. Repros plans to file an NDA for Androxal at the end of 2014.

November 12, 2012

Novartis reported results from a phase IV trial of once-yearly Aclasta for the prevention of spine fractures in men with osteoporosis. This randomized, placebo-controlled, parallel-group study enrolled 1,199 males ages 50 to 85 with primary osteoporosis or osteoporosis associated with low serum testosterone levels. Subjects received Aclasta or placebo as an annual 15-to-30-minute intravenous infusion at baseline and at 12 months. Patients also received daily calcium 1,000-1,500mg and vitamin D 800-1200IU. Data showed a significant reduction in the risk of spine fractures by 67% versus placebo over two years (p=0.002). The results also showed Aclasta reduced the risk of one or more new moderate-to-severe spine fractures by 81% at month 12 (p=0.01) and 63% at month 24 (p=0.03) compared with the placebo group. In addition, Aclasta produced significant and sustained improvements in bone mineral density at the spine and hip bones (lumbar spine, total hip and femoral neck bone [p≥0.05 for all comparisons]) and reduced the risk of height loss (-2.2mm and -4.5mm at month 24 for Aclasta and placebo [p=0.002], respectively). The drug was well tolerated. The most frequent adverse events were similar between treatment groups.

October 22, 2012

Merck issued results from a phase II trial of odanacatib for the treatment of osteoporosis. This randomized, double-blind, placebo-controlled, multi-center study enrolled 243 women with post-menopausal osteoporosis who had been previously treated with alendronate. Patients were at least 60 years of age with low Bone Mineral Density (BMD) T-scores (=-2.5 and >-3.5) at any hip site. Subjects received odanacatib 50mg or placebo once weekly for 24 months. All subjects received vitamin D3 (5600IU/week) and also calcium supplementation, if needed. Data demonstrated that odanacatib (compared to placebo) significantly increased BMD at all three hip sites (+1.73%, +1.83%, +0.83% for the femoral neck, hip trochanter and total hip, respectively, versus -0.94%, -1.35%, -1.87% with placebo), and the lumbar spine (+2.28% versus -0.30% change with placebo). At the distal forearm, BMD changes from baseline at 24 months were -0.92% and -1.14%, which was not statistically significant. Odanacatib was well tolerated. The most frequent adverse events were urinary tract infection, back pain, arthralgia, fractures, bronchitis, nasal pharyngitis and upper respiratory infection. Based on these data, Merck anticipates submitting regulatory applications for odanacatib in the U.S. and E.U. in the first half of 2013, and in Japan in the second half of 2013.

February 27, 2006

Amgen reported positive interim results of a phase II trial of denosumab (AMG 162), a RANK ligand inhibitor, for the treatment of low bone mineral density (BMD). Twice-yearly administration of the drug was shown to increase total hip BMD by 1.9% to 3.6% at 1 year, compared to a loss of 0.6% for placebo (p<0.001); this gain was non-inferior to a 2.1% gain for subjects receiving weekly doses of the approved drug Fosamax. Gains were also seen in lumbar spine BMD (3.0% to 6.7%, vs. -0.8%; p<0.001), distal 1/3 radius BMD (0.4% to 1.3%, vs. -2.0%; p<0.001), and total body BMD (0.6% to 2.8%, vs. -0.2%; p<0.01). Secondary data indicated a rapid onset of action, with target serum levels of C-telopeptide (a bone resorption biomarker) achieved within 72 hours. This ongoing multi-center dose-ranging study enrolled 412 healthy postmenopausal women with low BMD, who received 1 of 3 doses of the drug (6 mg, 14 mg or 30 mg) every 3 months or 1 of 4 (14 mg, 60 mg, 100 mg or 210 mg) doses of the drug every 6 months, or placebo, or an open-label regimen of 70 mg Fosamax once weekly, for 1 year.

October 11, 2004

Amgen has issued positive results from a phase II study of AMG 162, their investigational monoclonal antibody for the treatment of low bone mineral density (BMD). Interim results indicated that an injection of the drug administered twice during the first year of the study produce significant increases in total hip BMD compared to placebo, the trial’s primary endpoint. Data also demonstrated that the increases in total hip BMD at all trial doses were comparable or superior to those observed with standard weekly administration of Fosamax, an approved low-BMD therapy, the trial’s secondary endpoint; this effect was statistically significant (p<0.001) at a dose of 60 mg AMG 162 twice yearly. This ongoing, multi-center, dose-ranging study randomized a total of 411 postmenopausal women with low lumbar spine BMD to receive one of three doses AMG 162 every three months (6 mg, 14 mg, or 30 mg), one of four doses every six months (14 mg, 60 mg, 100 mg or 210 mg), standard therapy with Fosamax (70 mg weekly), or placebo. Amgen announced that these results would help support their recently initiated pivotal phase III study.

October 14, 2002

Positive phase I/II clinical trial results were reported by OrthoLogic for Chrysalin, a thrombin-related peptide being investigated for accelerated tissue and bone repair. The trial consisted of a randomized, double-blind, placebo-controlled study of 90 subjects in seven clinical centers to evaluate the safety and efficacy of Chrysalin. The drug showed no adverse events and no difference in adverse events between the Chrysalin-treated and placebo control groups. Chrysalin (10µg) treatment showed a positive effect based on radiographic assessment of cortical bridging, global radiographic healing and trabecular bridging. The time when 50% of the subjects are healed occurred 10.6 days faster for subjects treated with the 10µg dose than for those treated with placebo. The time when 70% we healed occurred 13.1 days faster.

March 5, 2002

Phase II trial results suggest that Novartis' intravenous zoledronic acid is as effective in increasing bone mineral density as oral daily or weekly bisphosphonates. The placebo-controlled trial, which was conducted at 25 centers, included 351 women with postmenopausal osteoporosis. In the zoledronic acid groups, subjects received 0.25 mg, 0.5 mg or 1.0 mg every three months, 2.0 mg at study onset and six months, or 4 mg only at study onset. At 12 months, bone mineral density was significantly increased from baseline in all dosing groups.