Bone Fractures

February 6, 2017

Radius Health issued results of a phase III trial of abaloparatide-SC 80mcg to reduce the risk of vertebral and nonvertebral fractures. The trial was a randomized, double-blind, placebo-controlled, comparative, multicenter, 18 month international study in 2,463 postmenopausal women with osteoporosis. The results of ACTIVExtend following six months of alendronate treatment show that patients previously treated with daily abaloparatide-SC for 18 months in the ACTIVE trial who were transitioned to alendronate had significantly greater reduction of 87% in the incidence of new vertebral fractures (p<0.001), of 52% in nonvertebral fractures (p=0.02) and 58% in major osteoporotic fractures (p<0.01) compared to the previous placebo treated patients who were also transitioned to alendronate. Bone mineral density at the spine, femoral neck and hip increased significantly in the abaloparatide-treated patients after transitioning to alendronate (p<0.0001). The initial separation of incidence of nonvertebral fractures on the Kaplan-Meier curve during ACTIVE for the abaloparatide-SC treated patients versus placebo continued into the first six months of alendronate treatment during ACTIVExtend, and the early separation in the incidence of major osteoporotic fracture continued to diverge over time. The only treatment-emergent AE that occurred in more than 4% of patients was arthralgia, and the incidence was similar between both groups. A New Drug Application for abaloparatide is currently under review by the FDA.

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.

July 6, 2015

Radius Health reported results of a phase III trial of abaloparatide for osteoporotic fractures. Radius previously reported positive results for the ACTIVE Trial, meeting the primary endpoint of new vertebral fracture reduction (-86%, p<0.0001) and secondary endpoints of non-vertebral fracture reduction (-43%, p=0.0489) and BMD increases at spine (18M, 9.20% p<0.0001), femoral neck (18M 2.90% p<0.0001) and total hip (18M 3.44% p<0.0001). ACTIVExtend results show that the group previously treated with abaloparatide had no new vertebral fractures during the first six months on alendronate. From the start of the ACTIVE study, this group showed an 87% reduction in new vertebral fractures (p<0.0001), 52% reduction in non-vertebral fractures (p=0.0168), 48% reduction in clinical fractures (p=0.0139) and a 58% reduction in major osteoporotic fractures (p=0.0122) over the 25-month period. A recent exploratory analysis showed that, for major osteoporotic fractures, there was a 67% reduction in major osteoporotic fractures (p=0.0014) for the abaloparatide treatment group v. placebo, and a 53% reduction in major osteoporotic fractures (p=0.0437) for the abaloparatide treatment group as compared to teriparatide. Over the 25-month period, patients in the abaloparatide-alendronate treatment group on average achieved a 12.8% increase in BMD at the lumbar spine, a 5.5% increase in BMD at total hip and a 4.5% increase in BMD at the femoral neck. In this treatment group, 20.4% of patients achieved a 6% increase or greater in BMD at all three sites (i.e., lumbar spine, total hip and femoral neck). The company is preparing regulatory submissions.

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.

May 9, 2011

Kuros Biosurgery released results from a phase IIb trial of KUR-113 for open tibial shaft fractures. This European-based, randomized, controlled, open-label, study enrolled 200 subjects. The subjects received KUR-113 (0.133, 0.4 or 1.0 mg/ml) in combination with standard of care (SOC) or SOC alone. The primary endpoint was the proportion of subjects healed at six months after surgery for each group. In the intent-to-treat population, the healing rate at six months after surgery, as assessed using radiographic and clinical criteria, was 76%, 80%, and 69% for the three KUR-113 dose groups, respectively, versus 65% for the SOC alone group. In the Per-Protocol population, the healing rates were 74%, 83%, and 75% for the KUR-113 groups, respectively, versus 63% in the SOC alone group. KUR-113 was determined to be safe and well tolerated.

October 1, 2007

Novartis announced positive results from a phase III trial of Aclasta for the prevention of new clinical fractures following a hip fracture. This trial, dubbed the Recurrent Fracture Trial, enrolled 2,100 subjects who were treated with placebo or Aclasta following the surgical repair of a low-trauma hip fracture. Treatment with Aclasta was shown to significantly reduce the risk of all of new clinical fractures by 35% compared to placebo (92 versus 139 fractures). The risk of new spine fractures was reduced by 46% (21 versus 39 fractures) and new non-spine fractures by 27% (79 versus 107 fractures). In addition, fewer subjects who received Aclasta following a fracture died compared to those who received placebo (9.6% versus 13.3%). Treatment was well tolerated, with Aclasta similar to placebo in safety and tolerability profiles. Based on the results, Novartis plans to submit regulatory filings by the end of 2007 to broaden the treatment indication of Aclasta.

September 5, 2006

OrthoLogic Corp. issued negative results of an interim analysis from a phase IIb trial of Chrysalin, for the treatment of unstable, displaced distal radius fractures. This double-blind, randomized, placebo-controlled, multi-site, five-arm dose-response study enrolled 274 subjects. Subjects were randomized to receive a single 1 mL percutaneous injection of Chrysalin at one of five doses, 0 (placebo), 1, 3, 10, and 30 ug, administered into the fracture site. They were than evaluated at 1-8, 10, 12, 26 and 52 weeks post-surgery. The trial failed to meet the primary endpoint of time to removal of immobilization devices, based on clinical and radiographic assessments of healing; treatment with Chrysalin did not demonstrate a superior benefit over placebo in this area. The trial was unsuccessful in meeting secondary endpoints of radiographic healing and dose response relationship as well, with neither of these observed during analysis. Based on these results OrthoLogic terminated this trial but planned to further evaluate the data for other development options.

March 27, 2006

Aastrom announced preliminary results of a phase II trial of their Tissue Repair Cells, for the treatment of non-union fractures, at the combined Orthopaedic Research Society and American Academy of Orthopaedic Surgeons meetings in Chicago. 7 patients had completed 6 months of treatment in the pilot phase to date; among these subjects, no incidence of TRC-related adverse events, morbidity at the marrow aspirate site, or change in serum biochemistry or white blood cell counts were observed. 2 patients experienced adverse events (acute infections) related to surgical intervention, which were subsequently resolved. Preliminary efficacy data were also positive, with radiographic bony callus formation observed in 4 patients at week 12 and all 7 subjects at week 24. Further, serum alkaline phosphatase levels (an indicator of bone formation) increased by 24% at 2 weeks. 36 patients with non-union tibial fractures were to be treated with the drug at the Lutheran General Hospital in Park Ridge Illinois, under the direction of Dr. Matthew L. Jimenez. Patients were treated in two trial phases: 11 patients were to be treated in an open-label pilot phase, followed by an expanded phase with the remaining 25 subjects.

January 2, 2006

Aastrom Biosciences has issued positive results of a clinical trial of their Tissue Repair Cells for maxillary bone reconstruction. Results from the study yielded a positive overall safety profile, and indicated preliminary efficacy: subjects experienced a statistically significant increase in bone height at 3 months, and evidence of bone graft integration was noted at 4 months. Further, the magnitude of bone height increased was statistically superior to the current standard of care (applied as an internal concurrent control to the other side of subjects' maxillae). Also, none of the TRC treated sites experienced bruising or swelling, vs. 3 of the control sites. This open-label feasibility study enrolled 5 subjects at the Teknon Hospital Maxillofacial Clinic in Barcelona, Spain.

February 7, 2005

Aastrom Biosciences announced the achievement of predefined clinical milestones in their phase I/II trial of their investigational TRC (Tissue Repair Cell) product, for the use in bone grafting/regeneration procedures and the treatment of bone fractures. Data from the study net predefined safety endpoints in the treatment of patients with long-term non-union tibial fractures, allowing the company to expand into the phase II stage of the trial and enroll patients with appendicular, or fresh, non-union fractures. The phase I stage of this open-label study was conducted at the Lutheran General Hospital in Park Ridge, IL; the phase II stage will expand the trial to include two additional US sites.

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