Post-Menopausal Osteoporosis

January 19, 2015

Radius Health released results of a phase III trial investigating abaloparatide-SC for potential use in the reduction of fractures in postmenopausal osteoporosis. The ACTIVE pivotal phase III fracture prevention trial for the investigational drug abaloparatide was a randomized, double-blind, placebocontrolled trial in postmenopausal osteoporotic women randomized to receive daily doses of one of the following for 18 months: 80 micrograms (μg) of abaloparatide, a matching placebo or the approved dose of 20μg of teriparatide. The trial enrolled 2,463 patients at 28 medical centers in 10 countries in the U.S., Europe, Latin America and Asia. The study enrolled otherwise healthy ambulatory women ages 50 to 85 (inclusive) who had been postmenopausal for at least five years. On the primary endpoint, the investigational drug abaloparatide-SC (n=690, fracture rate 0.72%) achieved a statistically significant 83% reduction of incident vertebral fractures as compared to the placebo-treated group (n=711, fracture rate 4.36%) (p<0.0001). The ACTIVE trial included an open-label teriparatide [rDNA origin] injection treatment group (n=717, fracture rate 0.98%) that showed a statistically significant 78% reduction of incident vertebral fractures as compared to the placebo-treated group (p<0.0001). On the secondary endpoints as compared to placebo, abaloparatide-SC achieved a statistically significant fracture-rate reduction of 43% in the adjudicated non-vertebral fracture subset of patients; a statistically significant reduction of 41% in the adjudicated clinical fracture group, which includes both vertebral and non-vertebral fractures; and a statistically significant difference in the time to first incident non-vertebral fracture in both the adjudicated non-vertebral fracture and the clinical fracture subset of patients. The company plans to file an NDA in the second half of 2015.

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.

November 14, 2011

Unigene released results from a phase II trial of their oral parathyroid (PTH) hormone for the treatment of postmenopausal osteoporosis. This double blind, placebo controlled, randomized, repeat dose trial enrolled 93 women. The study design included an open label comparator arm of the Forsteo injectable formulation. The subjects received a once daily treatment with 5mg oral PTH for 24 weeks. The primary endpoint was an increase in bone mineral density at the lumbar spine at 24 weeks compared to baseline. Oral PTH resulted in a statistically significant mean increase in BMD at the lumbar spine of 2.2% (p<0.001) at week 24 as compared to baseline. The Forsteo comparator arm also showed a statistically significant increase in BMD compared to baseline while the placebo arm showed a non-significant decline. There were no drug-related serious adverse events and no occurrences of hypercalcemia.

May 2, 2011

Amgen and UCB released results from a phase II trial of AMG785 for postmenopausal osteoporosis. This 12-month, multi-center, international, randomized, placebo-controlled, parallel-group study enrolled approximately 400 postmenopausal women with low bone mineral density (T-scores between -2.0 and -3.5). Dosing was administered at 70, 140 and 210 mg subcutaneously once a month or 140 and 210 mg every three months, against matched placebo for all treatment groups. The trial met the primary endpoint, demonstrating significant increases in lumbar spine bone mineral density at month 12 for the AMG 785 active arms versus the placebo arm. In addition, AMG 785 compared positively with two active comparators, teriparatide and alendronate. The overall incidence of adverse events was generally balanced between groups.

April 4, 2011

Tarsa Therapeutics reported results from a phase III trial of oral recombinant salmon calcitonin for postmenopausal osteoporosis. This multinational, randomized, double-blind, placebo-controlled trial, ORACAL, enrolled 565 postmenopausal women who were administered once daily oral calcitonin tablets or active comparator, synthetic salmon calcitonin nasal spray. The primary endpoint was the percent change in lumbar spine bone mineral density (BMD) after one year of treatment. Success required that oral salmon calcitonin be superior to placebo and non-inferior to nasal salmon calcitonin spray in increasing BMD at the lumbar spine. Both results were positive and statistically significant. The tolerability of oral calcitonin was similar to that of nasal calcitonin and placebo.

April 20, 2009

Eli Lilly issued positive results from a phase III trial of arzoxifene for the treatment of postmenopausal osteoporosis. This double-blind, two-year, multi-center trial, dubbed FOUNDATION, enrolled 331 postmenopausal women with normal or low bone mass. The subjects were randomized to receive arzoxifene 20 mg/day or placebo; all subjects received elemental calcium 500 mg/day. The primary endpoints were change in lumbar spine and total hip BMD. At two years, arzoxifene significantly increased the lumbar spine BMD by 2.9% versus placebo (arzoxifene, 1.6%; placebo, -1.3%, p<0.001); and total hip BMD by 2.2% versus placebo (arzoxifene 1.1%; placebo, -1.1%, p<1.001). Arzoxifene significantly decreased biochemical marker of bone resorption C-terminal cross-linking telopeptide of type I collagen (arzoxifene -30.01%, placebo 3.79%; p<0.001); and biochemical marker of bone formation serum N-terminal propeptide of type I collagen (arzoxifene -38.81%, placebo -10.27%; p<0.001). There was no significant difference overall in the number of adverse events in the arzoxifene group compared with the placebo group, with the exception of vaginal yeast infection (arzoxifene 4%, placebo 0%, p≡0.02). In addition, there were no significant differences in the incidence of endometrial hyperplasia or cancer between the arzoxifene and placebo groups or in endometrial thickness.

March 30, 2009

Eli Lilly reported positive results from a phase III trial of arzoxifene for the treatment of post-menopausal osteoporosis. This randomized, double-blind trial, dubbed NEXT, enrolled 320 post-menopausal women with osteoporosis in the US, Canada, the EU and Taiwan. The subjects received 20 mg/day of arzoxifene or 60 mg/day of raloxifene for 12 months. The primary endpoint was percentage change from baseline to 12 months in lumbar spine bone mineral density (BMD). Secondary endpoints were BMD measures of total hip and femoral neck. Arzoxifene increased lumbar spine, femoral neck and hip BMD by 2.8%, 1.5% and 1.5%, respectively, compared with 1.7, 0.5 and 0.8%, respectively, for raloxifene. Arzoxifene also significantly suppressed bone turnover, to a greater degree than raloxifene. Reported adverse events were similar between the two cohorts.

February 4, 2008

Amgen reported positive results from a clinical trial of denosumab for the treatment of low bone mineral density (BMD). This head to head trial enrolled one thousand one hundred and eighty nine women with postmenopausal osteoporosis who were randomized to receive twice-yearly subcutaneous injections of denosumab or weekly oral doses of alendronate (Fosamax). They were subsequently followed for one year to assess changes in BMD. The primary endpoint was the effect of denosumab on percent change from baseline in BMD at the total hip compared to alendronate. This was achieved; the relative magnitude of BMD improvement at the total hip was approximately 40% greater in the denosumab versus the alendronate group. The denosumab arm reached all secondary endpoints as well, with significant improvements over alendronate on percent change from baseline in BMD at the lumbar spine, hip trochanter, femoral neck and distal radius. Phase III trials of denosumab are currently underway.

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.