ACTIVExtend trial demonstrated statistically significant fracture risk reduction through the 3.5 years of sequential therapy: TYMLOS followed by alendronate
WALTHAM, Mass., Sept. 10, 2017 (GLOBE NEWSWIRE) -- Radius Health, Inc. (Nasdaq:RDUS), a science-driven biopharmaceutical company committed to developing and commercializing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases, today presented results from the completed ACTIVExtend study in an abstract titled "Sustained Fracture Risk Reduction with Sequential Abaloparatide/Alendronate: Results of ACTIVExtend" at the ASBMR 2017 Annual Meeting in Denver, Colorado.
In ACTIVExtend, patients who had completed 18 months of TYMLOS or placebo in the ACTIVE Phase 3 trial were transitioned to receive 24 additional months of open-label alendronate. Patients who received this sequential therapy demonstrated statistically significant fracture risk reductions through 3.5 years.
"Anabolic therapy with abaloparatide is highly effective for postmenopausal women at increased risk of osteoporotic fracture. However, it is essential to consolidate the gains in bone mass achieved with an anabolic with an antiresorptive agent," said Henry G. Bone, MD, FACP, FACE, lead author and Director of the Michigan Bone & Mineral Clinic, P.C., and head of Endocrinology and Metabolism at St. John Hospital and Medical Center, Detroit, MI. "In the ACTIVExtend trial, the increased bone mass and reduced fracture risk achieved with abaloparatide were maintained and extended with alendronate, a low cost antiresorptive agent."
At the 43-month timepoint, the previous TYMLOS-treated patients had a significant 84 percent relative risk reduction (p<0.0001) in the incidence of new vertebral fractures compared with women who received placebo followed by alendronate. Additionally, TYMLOS followed by alendronate demonstrated a 39 percent relative risk reduction in nonvertebral fractures (p=0.038), compared with women who received placebo followed by alendronate.
"We are extremely pleased with the results of the ACTIVExtend trial, which demonstrated sustained reductions in both vertebral and nonvertebral fractures," said Bruce Mitlak, MD, Vice President of Clinical Development, Radius Health. "An additional exploratory analysis showed a statistically significant risk reduction in hip fractures in the TYMLOS-treated patients who were transitioned to alendronate compared with women who received placebo followed by alendronate. The total number of hip fractures across the trial were limited (five) and all were within the placebo/alendronate arm."
ACTIVExtend bone mineral density (BMD) findings are also being presented at the Annual Meeting tomorrow, Monday, September 11, 2017 in the poster presentation titled: "Bone Mineral Density and Bone Turnover Marker Changes with Sequential Abaloparatide/Alendronate: Results of ACTIVExtend" (Bilezikian).
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF OSTEOSARCOMA
- Abaloparatide caused a dose-dependent increase in the incidence of osteosarcoma (a malignant bone tumor) in male and female rats. The effect was observed at systemic exposures to abaloparatide ranging from 4 to 28 times the exposure in humans receiving the 80 mcg dose. It is unknown if TYMLOS will cause osteosarcoma in humans.
- The use of TYMLOS is not recommended in patients at increased risk of osteosarcoma including those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, bone metastases or skeletal malignancies, hereditary disorders predisposing to osteosarcoma, or prior external beam or implant radiation therapy involving the skeleton.
- Cumulative use of TYMLOS and parathyroid hormone analogs (e.g., teriparatide) for more than 2 years during a patient's lifetime is not recommended.
Orthostatic Hypotension: Orthostatic hypotension may occur with TYMLOS, typically within 4 hours of injection. Associated symptoms may include dizziness, palpitations, tachycardia or nausea, and may resolve by having the patient lie down. For the first several doses, TYMLOS should be administered where the patient can sit or lie down if necessary.
Hypercalcemia: TYMLOS may cause hypercalcemia. TYMLOS is not recommended in patients with pre-existing hypercalcemia or in patients who have an underlying hypercalcemic disorder, such as primary hyperparathyroidism, because of the possibility of exacerbating hypercalcemia.
Hypercalciuria and Urolithiasis: TYMLOS may cause hypercalciuria. It is unknown whether TYMLOS may exacerbate urolithiasis in patients with active or a history of urolithiasis. If active urolithiasis or pre-existing hypercalciuria is suspected, measurement of urinary calcium excretion should be considered.
Adverse Reactions: The most common adverse reactions (incidence ≥2%) are hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain and vertigo.
INDICATIONS AND USAGE
TYMLOS is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures.
Limitations of Use
Because of the unknown relevance of the rodent osteosarcoma findings to humans, cumulative use of TYMLOS and parathyroid hormone analogs (e.g., teriparatide) for more than 2 years during a patient's lifetime is not recommended.
For the TYMLOS prescribing information, including Boxed Warning, please visit www.tymlospi.com.
About Postmenopausal Osteoporosis
Osteoporosis is a silent disease, often displaying no signs or symptoms until a fracture occurs, leaving a majority of patients undiagnosed and undertreated. Osteoporotic fractures create a significant healthcare burden, and represent a significant unmet medical need. The majority of osteoporosis-related fractures in the U.S. among those 50 and older (71 percent) occur in women.
The National Osteoporosis Foundation (NOF) has estimated that nearly 8.2 million women in the U.S. over the age of 50 have osteoporosis, and nearly one in two women over the age of 50 will have a fragility fracture (or low-impact fracture that is often the result of a fall from standing height or lower) in her remaining lifetime.
The annual incidence of osteoporotic fractures is higher than that of stroke, heart attack and breast cancer combined; osteoporotic fractures also account for more hospitalizations and associated costs than cardiovascular disease and breast cancer.
About ACTIVE and ACTIVExtend
The Phase 3 ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial was a randomized, double-blind, placebo-controlled, comparative, multicenter, 18-month international study in 2,463 postmenopausal women with osteoporosis designed to evaluate the efficacy and safety of abaloparatide-SC 80 mcg to reduce the risk of vertebral and nonvertebral fractures. The results of ACTIVE were published in the Journal of the American Medical Association in August of 2016. ACTIVExtend, an extension of ACTIVE, enrolled patients who had completed 18 months of abaloparatide-SC or placebo in ACTIVE to receive up to 24 additional months of open-label alendronate. The results of the first six months of ACTIVExtend were published in the Mayo Clinic Proceedings in February of 2017.
About TYMLOS (abaloparatide)
TYMLOS (abaloparatide) was approved by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. Radius' Marketing Authorisation Application (MAA) for abaloparatide-SC for the treatment of women with postmenopausal osteoporosis was validated and is currently undergoing regulatory review by the European Medicines Agency (EMA).
Radius also is developing abaloparatide-transdermal (abaloparatide-TD) based on 3M's patented Microstructured Transdermal System technology for potential use as a treatment for postmenopausal women with osteoporosis.
Radius is a science-driven fully integrated biopharmaceutical company that is committed to developing and commercializing innovative therapeutics in the areas of osteoporosis, oncology and endocrine diseases. Radius' lead product, TYMLOS (abaloparatide) injection, was approved by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture. The Radius clinical pipeline includes an investigational abaloparatide transdermal patch for potential use in osteoporosis and the investigational drug elacestrant (RAD1901) for potential use in hormone-driven and/or hormone-resistant breast cancer, and vasomotor symptoms in postmenopausal women. Radius' RAD140, a non-steroidal, selective androgen receptor modulator (SARM), is under investigation for potential use in hormone receptor positive breast cancer. For more information, please visit www.radiuspharm.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding expectations of the significance of clinical trial data for TYMLOS, the potential benefit of treatment with TYMLOS for postmenopausal women with osteoporosis, the progress of abaloparatide-SC in the regulatory process with the EMA, and the potential clinical uses for abaloparatide-TD, elacestrant (RAD1901) and RAD140.
These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we expect to need to raise additional funding, which may not be available; risks related to raising additional capital; our limited operating history; quarterly fluctuation in our financial results; our dependence on the success of TYMLOS, and our inability to ensure that TYMLOS will obtain regulatory approval outside the U.S. or be successfully commercialized in any market in which it is approved, including as a result of risk related to coverage, pricing and reimbursement; risks related to competitive products and any collaboration agreements failing to be successful; risks related to clinical trials, including our reliance on third parties to conduct key portions of our clinical trials and uncertainty that results will support our product candidate claims; the risk that adverse side effects will be identified during the development of our product candidates or during commercialization, if approved; risks related to manufacturing, supply and distribution; and the risk of litigation or other challenges regarding our intellectual property rights. These and other important risks and uncertainties discussed in our filings with the Securities and Exchange Commission, or SEC, including under the caption "Risk Factors" in our most recent Quarterly Report on Form 10-Q and subsequent filings with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.
Investor Relations Contact:
Tiffany H. Burke