September 12, 2016
Amgen released phase III top-line results of the randomized, double-blind, double-dummy, active-controlled study evaluating the safety and efficacy of Prolia (denosumab) compared with risedronate in patients receiving glucocorticoid treatment. The international, multicenter, parallel-group study enrolled 795 patients adults in the 24-month study to evaluate the safety and efficacy of treatment with Prolia 60mg subcutaneously every six months compared with oral risedronate 5mg daily in two patient subpopulations: 505 patients receiving continuing glucocorticoid therapy (defined as patients receiving greater than or equal to 7.5mg daily prednisone or its equivalent for three months or longer and planning to continue treatment for a total of at least six months) and 290 patients newly initiating glucocorticoid therapy (defined as patients receiving greater than or equal to 7.5mg daily prednisone or its equivalent for less than three months and who are planning to continue treatment for a total of at least six months). The study met all primary and secondary endpoints at 12 months. The data showed that treatment with Prolia for 12 months, compared to risedronate, led to significantly greater gains in bone mineral density (BMD) at the lumbar spine and total hip, both in patients receiving continuing glucocorticoid therapy and in patients newly initiating glucocorticoid therapy. Results from the glucocorticoid-induced osteoporosis study showed that, in patients receiving continuing glucocorticoid therapy, Prolia treatment led to greater gains in BMD, compared with risedronate, both at the lumbar spine (4.4% vs. 2.3%, respectively) and total hip (2.1% vs. 0.6%, respectively). Similarly, in patients newly initiating glucocorticoid therapy, Prolia treatment led to greater increases in BMD, compared with risedronate, both at the lumbar spine (3.8% vs. 0.8%, respectively) and total hip (1.7% vs. 0.2%, respectively). The study remains double-blinded and ongoing for an additional 12 months.
August 29, 2016
Radius Health issued results of a phase III trial of abaloparatide for the treatment of postmenopausal women with osteoporosis. The randomized, double-blind, placebo-controlled, comparative, multicenter, 18-month international study enrolled 2,463 women. The study was designed to evaluate the efficacy and safety of the investigational drug abaloparatide-SC 80mcg to reduce the risk of vertebral and nonvertebral fractures. The ACTIVE results showed that patients treated with daily abaloparatide for 18 months had a significantly greater reduction in the incidence of new vertebral fractures (p<0.001) and nonvertebral fractures (p=0.049) compared to placebo. An NDA for abaloparatide is currently under review by the FDA.
April 18, 2016
Amgen and UCB issued results of a phase III study of romosozumab compared with teriparatide in postmenopausal women with osteoporosis. The randomized, open-label, international, multicenter trial included 436 women, averaging 72 years of age, with postmenopausal osteoporosis, a history of non-vertebral fracture after the age of 50, or vertebral fracture and treatment with bisphosphonate therapy for a minimum of three years prior to transitioning to romosozumab or teriparatide therapy. The women were randomly assigned to receive either subcutaneous romosozumab 210mg once monthly (n=218) or subcutaneous teriparatide 20mcg daily for 12 months (n=218). The results showed that the percent change from baseline in BMD at the total hip through month 12 (the primary endpoint, an average of the percent change from baseline at month six and 12), was significantly greater with romosozumab compared with teriparatide: 2.6% v. –0.6%, respectively. The overall incidence of adverse events was generally balanced between the two study arms. Incidence of all adverse events in patients treated with romosozumab was 75.2% compared to 69.2% with teriparatide. Serious adverse events occurred in 7.8% of patients treated with romosozumab compared to 10.7% for teriparatide. Adverse events reported in the romosozumab arm greater than or equal to 10% of patients were arthralgia and nasopharyngitis. Injection site reactions were reported in 7.8%.
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.
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.
January 20, 2014
Radius Health reported results of a phase
II study of BA058 (abaloparatide) for the
treatment of osteoporosis. A total of 250
healthy postmenopausal women with
osteoporosis were enrolled in this randomized,
placebo-controlled study designed
to evaluate the efficacy and tolerability of
abaloparatide administered via a novel, short
wear-time transdermal patch delivery system
compared to subcutaneous injection delivery
of abaloparatide. At baseline, the mean age
of the randomized patients was 66.2 years,
and the mean t-score [bone mineral density
(BMD) compared with what is normally
expected in a healthy young woman] for
spine and total hip were -2.33 and -1.47,
respectively. Of randomized patients, 39%
had a history of fracture. Patients were
randomized to receive either Abaloparatide
TD (50μg, 100μg or 150μg), transdermal
placebo, or Abaloparatide SC (80μg—the
same dose being studied in the ongoing
phase III study) once daily for six months.
The transdermal patches were applied to the
skin and removed after five minutes. Each of
the three doses of Abaloparatide TD patch
at the six-month endpoint demonstrated a
statistically significant lumbar spine BMD
increase from baseline versus placebo, with
the 150μg dose showing the greatest gains
(2.95% increase, p value less than 0.0001) v.
placebo (0.04% increase). Both the 100μg
and 150μg doses demonstrated a statistically
significant increase in total hip BMD compared
to baseline, with the 150μg dose again
showing the greatest gain (1.49% increase,
p=0.0018 ) v. placebo (0.02% decrease).
Consistent with a previous phase II study of
Abaloparatide SC, patients who received the
80μg dose of Abaloparatide SC demonstrated
consistent increases in BMD in both lumbar
spine (5.80% increase from baseline) and hip
(2.74% increase from baseline).
May 27, 2013
Medivir reported results from a phase Ia trial of MIV-711 for osteoarthritis and osteoporosis. This double-blind, placebo-controlled, randomized study enrolled nine patients with osteoarthritis and osteoporosis. Subjects received daily doses of MIV-711 20mg to 600mg, or placebo. Data demonstrated MIV-711 decreased serum levels of the bone resorption biomarker, CTX-I, in a dose-dependent manner. Maximal reduction occurred with 600mg dose (79 ± 4% reduction at 24 h post dose) and at the 100mg dose CTX-I levels were reduced by 51 ± 4% at 24 h post-dose compared to baseline levels. Anticipating a target reduction of circulating CTX-I levels of approximately 50%, the results indicate low doses will be sufficient for the desired pharmacological effects. MIV-711 was well tolerated. No apparent effects were seen on vital signs and no significant changes in hematology or clinical chemistry were observed. Based on this data, Medivir has initiated a phase Ib study of MIV-711 lasting four weeks. Data is expected to be available around mid-year.
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.
May 26, 2008
Amgen released positive results from a phase III trial of denosumab for the treatment of postmenopausal osteoporosis. This randomized, double-blind, active controlled, parallel group study enrolled 504 women with low bone mineral density (BMD) who had previously been treated with alendronate (Fosamax). The subjects received denosumab treatment (60 mg twice yearly) or continuing alendronate therapy (70 mg weekly) for twelve months. The primary endpoint was the effect of denosumab treatment on total hip BMD when compared to continuing alendronate therapy at 12 months. The primary endpoint was reached; the relative magnitude of BMD improvement at the total hip was approximately 80 percent greater in the denosumab versus the alendronate group. The secondary endpoints were reached as well, with significant BMD gains at all sites measured including lumbar spine, femoral neck, distal radius, and hip trochanter compared with the group that continued on alendronate. Adverse events were comparable between the treatment arms. Based on the results Amgen plans to continue with the development of denosumab.
November 19, 2007
Osteologix released positive results from a phase II trial of NB S101 for the treatment of osteoporosis. This twelve-week, double-blind, randomized, placebo and active-controlled study, dubbed STRONG, enrolled 289 postmenopausal women with low bone mineral density. The trial was designed to compare three dose levels of NB S101 (0.75 grams, 1 gram or 2 grams) to one dose level of Protelos, an approved therapy in Europe. The reductions in serum CTX-1 compared to the placebo group were 13.5%, 15.5% and 22.2% for the NB S101 0.75, 1 and 2 gram dose groups, respectively (p less than 0.001 for all doses versus control). In addition, in three months NB S101 significantly increased lumbar spine bone mineral density at all tested doses, with the 2 gram dose showing the most significant increase of 2.66% (p less than 0.01). Treatment was well tolerated, with all side effects mild to moderate in nature. Based on the results, Osteologix planned to continue with the development of NB S101.
September 24, 2007
Orthogen released positive results from a clinical trial of Orthokine for the treatment of osteoarthritis (OA). This randomized, prospective, placebo-controlled study, dubbed GOAT (German OsteoArthritis Trial) enrolled 376 subjects with OA of the knee joint. The subjects received Orthokine, hyaluronic acid, or placebo for six total treatment periods. Analysis of the subjects was conducted at six weeks, three months and six months using various measurements including the visual analogue scale (VAS) and the WOMAC questionnaire. At baseline the average VAS score was 70 (intense pain). After six months, 57% of the Orthokine group reported a 50-percent reduction compared to 29% and 28% for the hyaluronic acid and placebo groups, respectively. The Orthokine arm also showed improvements of over 50% on the WOMAC survey compared to 20% in the two other treatment arms. Based on the results, the development of Orthokine will continue.
Zelos issued positive results from a phase II extension trial of Ostabolin-C for the treatment of postmenopausal osteoporosis. This double-blind eight month trial enrolled 198 postmenopausal women who received one of four subcutaneous doses of Ostabolin-C (7.5, 15, 30 or 45 microgram/day) or placebo. The primary endpoint, a significant change in lumbar spine bone mineral density (LS-BMD) at one year, was achieved. A maximum mean LS-BMD increase of 11% was observed in all treatment groups. In the 45 microgram dose group, a clinically relevant LS-BMD increase of 3% or more was observed in 79% of the subjects after 4 months and 97% after 12 months. Significant increases in BMD of the hip were also observed. Based on the results, Zelos plans to move ahead with the development of Ostabolin-C.
July 16, 2007
TransPharma released positive results from a phase II trial of ViaDerm-hPTH for the treatment of osteoporosis. This trial enrolled 48 healthy, elderly, post-menopausal women. The trial was designed to evaluate the safety and tolerability of ascending multiple doses of ViaDerm hPTH patches, as well as to compare the pharmacokinetic profiles of transdermally delivered doses of ViaDerm hPTH to that of Forteo (standard of care), administered subcutaneously. Treatment was well tolerated, with adverse events similar between the two arms. Pharmacokinetic profiles in the first and seventh day were similar, showing no accumulation of hPTH (1-34) levels and no deterioration in hPTH (1-34) systemic levels. In addition, all doses of transdermally delivered ViaDerm hPTH showed desirable peak profiles with relative bioavailability of approximately 40%. Based on the results, TransPharma planned to begin additional phase II trials shortly.
May 14, 2007
Novartis released positive results from a phase III trial of Reclast for the treatment of postmenopausal osteoporosis. This randomized, placebo-controlled trial enrolled 7,700 postmenopausal women who received placebo or Reclast as a once yearly, 15 minute infusion. The primary endpoint was the number of new spine and hip fractures over three years compared to placebo. Secondary endpoints included reducing the incidence of non-spine fractures, evaluation of bone mineral density (BMD), normalization of bone turnover markers, and overall safety. Treatment with Reclast provided a 70% reduction in spine fractures and a 41% reduction in hip fractures over three years. Reclast reduced all non-spine, all clinical and all clinical spine fractures by 25%, 33% and 77%, respectively. In addition, bone mineral density increased significantly in the spine by 6.7% and the hip by 6% in women on Reclast compared to placebo. Reclast for this indication is currently under review by the FDA.
February 12, 2007
Zelos revealed positive results from a phase II trial of Ostabolin-C for the treatment of osteoporosis. This double blind, placebo controlled, dose ranging trial enrolled 261 postmenopausal women with moderate osteoporosis. Subjects were placed into one of five dose groups to receive Ostabolin-C (5, 10, 20 and 30 ug) or placebo daily via subcutaneous injection, for a four month duration. The primary endpoint was the percentage change in lumbar spine bone mineral density. Treatment was well tolerated with no unexpected adverse events. The principal endpoint was reached with an observed statistically significant, dose responsive increase in mean lumbar spine bone mineral density. This reached 5.2% at the highest dose tested. An eight month blinded extension study is underway to allow for the evaluation of 12 months of continuous treatment with Ostabolin-C. Results are expected in Q2 of 2007.
July 3, 2006
Nastech Pharmaceutical issued positive results of a phase I trial of PTH1-34, a nasal spray formulation of parathyroid hormone for the treatment of osteoporosis, at the 88th Annual Meeting of the Endocrine Society. This open-label study enrolled 25 healthy elderly male volunteers, who received a single injection of an approved subcutaneous formulation of PTH1-34 (teriparatide), followed by four successive intranasal doses of the drug. Trial data indicated up to 11% nasal bioavailability of the drug, relative to subcutaneous administration. No clinically significant changes in vital signs, electrocardiograms, nasal examinations, or laboratory evaluations were noted.
July 18, 2005
NicOx has issued positive results of a phase II trial of HCT 1026, their nitric-oxide-containing flurbiprofen derivative for the treatment of osteopenia (high bone turnover). NicOx is also investigating the drug for the treatment of Alzheimer's disease. Efficacy data met their primary efficacy endpoint, with 24% of subjects achieving at least a 40% reduction in serum levels of the bone- resorption marker CTX compared to baseline (p<0.001). Secondary efficacy was also established, with 25 % (6 of 24) of subjects achieving a significant reduction in urinary levels of the bone resorption market NTX (p<0.001). This open label, non-placebo controlled pilot study enrolled recently menopausal (<5 years) female osteopenic patients, who received 100 mg HCT 1026 twice daily for 6 months. NicOx announced that it planned to investigate potential lead compounds utilizing their nitric-oxide donating technology for the treatment of osteopenia and osteoporosis, and it did not expect to continue development of HCT 1026 for this indication.
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.
June 1, 2004
Androclus Therapeutics reported results from a phase I/IIa trial investigating AT-001 (dnaJP1), an engineered oral peptide for the treatment of rheumatoid arthritis (RA). Results demonstrated an induced a change from proinflammatory to regulatory T cell function. In addition, peptide-induced T cell production of IL-4 and IL-10 increased significantly while peptide-induced T cell proliferation and production of IL-2, interferon-gamma and TNF-alpha decreased significantly. Subjects were administered AT-001 orally for six months. Results from the open-label study were reported in the Proceedings of the National Academy of Sciences (March 23, 2004).
Theratechnologies and ALZA Corporation reported positive preliminary results from a phase I trial investigating ThPTH, a transdermal formulation of parathyroid hormone (PTH) for the treatment of osteoporosis. Results showed the rapid delivery and biologic activity of PTH, good bioavailability and a good safety profile. Data revealed that the patch delivered PTH, as measured by ELISA, at blood levels in the same range as subcutaneous administration. There were no serious adverse events reported. The first-in-human, cross-over design study enrolled 20 subjects. Subjects received a Macroflux-PTH patch and a subcutaneous injection of commercially available PTH (Forteo). The study was designed to determine the pharmacokinetic and pharmacodynamic profile of the Macroflux-PTH patch.<
April 5, 2004
NPS Pharmaceuticals reported positive results from a phase III trial investigating PREOS, a recombinant human parathyroid hormone for the treatment of osteoporosis. Results showed the study met the primary endpoint, reduction in the incidence of new or worsened vertebral fractures. Data demonstrated the rate of vertebral fractures in subjects taking PREOS was 1.4% compared with 3.4% in subjects taking placebo, a 59% reduction. The multi-center, randomized, double-blind, placebo-controlled study, called TOP (Treatment of Osteoporosis with PTH), enrolled 2,600 postmenopausal women with osteoporosis and was conducted at 152 sites worldwide. It was designed to evaluate the potential of PTH to reduce the risk of vertebral fracture in women. Subjects received PREOS (100-ug- daily) or placebo, plus daily supplements of calcium and vitamin over a period of 18 months. The primary endpoint was a reduction in the incidence of new or worsened vertebral fractures in patients receiving PREOS, compared to patients who received a placebo.
April 21, 2003
Merck reported positive results from a phase IV trial investigating Fosamax (alendronate sodium), a non-hormonal therapy for the treatment of osteoporosis. Results showed that female subjects who stopped taking standard hormone replacement therapy (HRT) lost significant bone loss. Furthermore, subjects who took Fosamax did not lose this bone mass. Data demonstrated that discontinuation of HRT resulted in a 3.2% loss in bone mineral density (BMD) at the lumbar spine over 12 months in subjects taking placebo. Subjects taking Fosamax experienced a 2.3% increase in BMD at the lumbar spine for a total difference of 5.5% between treatment groups. The 12-month, multicenter, double blind study enrolled 144 postmenopausal female subjects who had discontinued HRT within three months prior to the start of the trial.
February 10, 2003
The University of Pittsburgh School of Medicine reported positive results from a pilot study investigating Parathyroid Hormone Related Protein (PTHrP), a bone anabolic hormone for the treatment of osteoporosis. Results showed that the overall rate of bone density increase was 4.7 % over a three-month period. The findings compare favorably to results reported with the recently approved parathyroid hormone. The treatment was reported to be well tolerated, with no subjects developing hypercalcemia, hypotension, nausea, flushing or other adverse effects. The double blind, placebo-controlled randomized study enrolled 16 postmenopausal subjects with osteoporosis who had been on hormone replacement therapy for an average of eight years. Subjects received either a self-administered injection of PTHrP or placebo and were followed for three months.
May 20, 2002
Positive results were obtained from a randomized, double-blind, placebo-controlled phase III trial of teriparatide in men with osteoporosis. The trial included 437 subjects with idiopathic or hypogonadal osteoporosis, and the average age of the group was 59. Subjects received daily treatment with either 20 ug or 40 ug of teriparatide or placebo. Results demonstrated that bone mineral density (BMD) increased by 6-9% at the spine and by 1.5-3% at the hip. Significant spinal BMD increases were observed as early as three months, and 93-94% of subjects had a clinically favorable treatment response after the treatment period of approximately 11 months. Teriparatide is being developed by Eli Lilly.