Being Developed for the Potential Use in the Treatment of OsteoporosisSubcutaneous Injection
Investigational drug product candidate Abaloparatide-SC
Abaloparatide is a new synthetic peptide analog of hPTHrP (human parathyroid hormone-related protein), a naturally occurring bone building hormone. PTHrP, unlike parathyroid hormone, is critical in the formation of the skeleton, is involved in the regulation of bone formation, and is able to rebuild bone with low associated risk of inducing hypercalcemia as a side effect.
In two Phase 2 clinical trials, the investigational drug product candidate abaloparatide was administered through a subcutaneous injection (abaloparatide-SC) and produced faster and greater bone mineral density increases at the spine and the hip, with substantially less hypercalcemia than Forteo® (teriparatide).
In December 2014, we announced positive 18-month top-line data from our Phase 3 ACTIVE clinical trial of the investigational drug abaloparatide-SC for potential use in the reduction of fractures in postmenopausal osteoporosis. According to the top-line data, on the primary endpoint, abaloparatide-SC achieved a statistically significant reduction of incident vertebral fractures as compared to the placebo-treated group. On the secondary endpoints, as compared to placebo, abaloparatide-SC achieved a statistically significant fracture-rate reduction in the adjudicated non-vertebral fracture subset of patients; a statistically significant reduction in the adjudicated clinical fracture group; 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. Abaloparatide-SC also achieved statistically significant increases in BMD at the lumbar spine, total hip, and femoral neck at 6 months, 12 months, and 18 months.
Patients from the abaloparatide and placebo groups from our Phase 3 trial are eligible to continue in an extension study, ACTIVExtend, in which they are receiving an approved alendronate therapy for osteoporosis management. This study is fully enrolled and we expect 6-month results in the 2Q of 2015.
We believe that the abaloparatide-SC program is on-track for submission of an NDA for abaloparatide-SC to the FDA, and submission of an MAA to the European Medicines Agency, or EMA, in the second half of 2015. The results from the ACTIVE trial and the first six months of the ACTIVExtend trial, together with the entire data set from the abaloparatide development program, are subject to regulatory review, and only FDA and EMA can separately determine whether the data in the new drug application, once submitted, support approval of the investigational drug abaloparatide-SC for its potential use in the reduction of fractures in postmenopausal osteoporosis.
Abaloparatide-TD Being Developed for the Potential Use in the Treatment of Osteoporosis Transdermal Patch
Investigational drug product candidate Abaloparatide-TD
Results of a Phase 2 clinical trial provided initial evidence of efficacy, safety, and tolerability of abaloparatide-TD in the potential treatment of osteoporosis. At each dose, abaloparatide-TD demonstrated a statistically significant mean percent increase from baseline in bone mineral density (BMD) as compared to placebo at the lumbar spine and at the hip. These clear, proof-of-concept results indicated a dose-dependent increase in BMD. The clinical significance of these initial findings must be investigated in subsequent clinical trials, and all the resulting data are subject to regulatory review.
RAD1901Estrogen Receptor (ER+) Cancers: Being Developed for the Potential Use in the Treatment of Breast CancerOral
Investigational drug product candidate RAD1901
RAD1901 is a selective estrogen receptor down-regulator/degrader, or SERD, that crosses the blood-brain barrier and is being evaluated for the potential treatment of metastatic breast cancer. RAD1901 has been shown to bind with good selectivity to the estrogen receptor and to have both estrogen-like and estrogen-antagonistic effects in different tissues. The clinical significance of these initial findings must be investigated in clinical trials, and all the resulting data are subject to regulatory review. In many cancers, hormones, like estrogen, stimulate tumor growth, and thus a desired therapeutic goal is to block this estrogen-dependent growth while inducing apoptosis of the cancer cells. SERDs have the potential to be an emerging class of endocrine therapies that could directly induce estrogen receptor, or ER, degradation, thus potentially enabling them to remove the estrogen growth signal in ER-dependent tumors without allowing ligand-independent resistance to develop.
RAD1901 Being Developed for the Potential Use in the Treatment of Vasomotor SymptomsOral
Investigational drug product candidate RAD1901
RAD1901 is in development at lower doses as a selective estrogen receptor modulator, or SERM, for the potential treatment of vasomotor symptoms. In a Phase 2 proof-of-concept study, RAD1901 demonstrated a reduction in frequency and severity of moderate and severe hot flashes. The clinical significance of these initial findings must be investigated in subsequent clinical trials, and all the resulting data are subject to regulatory review.
RAD140 Being Developed for the Potential Use in the Treatment of Breast CancerOral
Investigational drug product candidate RAD140
RAD140 is a nonsteroidal selective androgen receptor modulator, or SARM. The androgen receptor (AR) is highly expressed in many estrogen receptor (ER)-positive, ER-negative, and triple-negative receptor breast cancers. Because of its receptor and tissue selectivity, potent oral activity, and long duration half-life, RAD140 could have clinical potential in the treatment of breast cancer. The clinical significance of these initial findings must be investigated in clinical trials, and all the resulting data are subject to regulatory review.