New Bone Building Agent Approved for Post-Menopausal Women

TYMLOS (abaloparatide), a new bone-building anabolic therapeutic agent for high fracture risk, older women, including those with diabetes or thyroid disease, gains Food and Drug Administration approval.

With Felicia Cosman, MD, and Dorothy A. Fink, MD

Following the Food and Drug Administration (FDA) approval of TYMLOS™ (abaloparatide, a parathyroid hormone-related peptide, from Radius Health Inc.),1 practitioners now have a new anabolic treatment for post-menopausal women who are at high risk of fracture. Studies suggest that abaloparatide is appropriate for first-line treatment of osteoporosis in high-risk postmenopausal women, 2-4 compatible with American Academy of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) osteoporosis guidelines.5

During the ACTIVE trial,2 a total of 2,463 women aged on average 69 years received either an injectable placebo, a daily 80 mcg subcutaneous injection of abaloparatide,, or a daily 20 mcg injection of teriparatide, a recombinant human parathyroid hormone. Abaloparatide showed a reduction in fractures and increases in bone mass density that was significantly better than placebo and comparable to results achieved with teriparatide, an anabolic agent approved in 2002.

“We’re really gratified with the FDA’s approval of TYMLOS (abaloparatide),” Felicia Cosman, MD, professor of clinical medicine at Columbia University College of Physicians and Surgeons in New York, New York, told EndocrineWeb. “It’s important to reinvigorate doctors’ interest in treating osteoporosis.  We have not been doing a good job treating the highest risk patients and abaloparatide is specifically approved for those post-menopausal women who have had osteoporosis or major fracture as well as women who have had very low bone mass even in the absence of an osteoporosis-related fracture in the past.”

New bone-building agent, TYMLOS (abaloparatide) approved by FDA for older women.

During the Phase III clinical trial,2 just 4 out of 690 patients taking abaloparatide were diagnosed with a new vertebral fracture. By contrast, 30 out of 711 patients taking placebo had a new vertebral fracture at that time. “So we know that we can see a dramatic reduction in the occurrence of new vertebral fractures in just 18 months,” said Dr. Cosman.  

Suitable Candidates for Osteoporosis Treatment

Dr. Cosman expects that high risk, post-menopausal women who are being treated for thyroid conditions or diabetes are also suitable candidates.

“We have not looked at the influence of diabetes specifically and would need a larger study group to evaluate that, but there’s no reason to think that diabetic patients would respond differently,” she said. “Of course both type one and type two diabetes are risk factors for osteoporosis and osteoporosis-related fractures in post-menopausal women.”

Product labeling indicates that this type of drug should not be taken by anyone for more than two years, and is never appropriate for breast cancer patients who have a history of treatment with radiation therapy.6

“The length of the treatment is governed in part by some studies that were done in rodents where the medication at high dose showed an increase in both benign and malignant tumors of the bone, called osteosarcoma,” she said. “One of the risk factors for osteosarcoma is radiation exposure to the skeleton, so that is not the type of patient we would want to use abaloparatide.

Clinical Bone Health Considerations

Dr. Cosman told EndocrineWeb that the ACTIVE trial showed “a slightly higher drop-out rate from the abaloparatide group due to side effects (9.9%) compared to the placebo group (6.1%) or the other active arm of the study (teriparatide group; 6.8%).” Also, she clarified distinctions between the study arms.

“The mechanism of action of the two medications (abaloparatide vs. teriparatide) is a bit different because of differences in the way the two molecules interact with the parathyroid hormone-1 receptor,” said Dr. Cosman. “Furthermore, the fracture efficacy data differ somewhat between abaloparatide and teriparatide, based on the findings of the ACTIVE study, particularly for certain non-vertebral fracture outcomes, especially at the wrist. Bone mineral density increased a bit more in the hip in the abaloparatide group.”

Other considerations could influence a clinician’s choice, as well.

“There may also be differences in tolerability between the two medications, differences in cost and insurance coverage, as well as an advantage with the lack of need for refrigeration of abaloparatide after the medication is opened,” said Dr. Cosman.

Two Years to Lock in Therapeutic Gains

The two-year maximum treatment period is sufficient to achieve significant results, said Dr. Cosman. “In the clinical world, we would treat with an anti-resorptive medication after abaloparatide. In fact, the ACTIVE study was extended such that all the women in the TYMLOS Group and in the placebo group were transitioned to an anti-resorptive therapy. In the ACTIVExtend trial, 4 women were transitioned to alendronate treatment, 70 mg once weekly.” The ACTIVExtend findings appeared in the Mayo Clinic Proceedings.4

Dr. Cosman and the team of investigators found that under the sequential protocol, patients showed a relative risk reduction of 87% of new morphometric vertebral fractures.4

“In the real world, we use anabolic therapy to try to build up the mass of bones and restore some of the structural deficits in the bone tissue in these women who are at high risk for fracture; and then we use the anti-resorptive therapy to close up the remodeling phase and put the bone to rest and maintain the benefits that were developed under the influence of abaloparatide," Dr. Cosman told EndocrineWeb.

Viable First-Line Option

“We are really happy that AACE/ACE came out and supported the use of anabolic therapy as first-line treatment for high-risk patients.  We think this is the best use of TYMLOS and we want to target these women who have had recent fractures,” said Dr. Cosman.

“We want to be very proactive about finding vertebral fractures. We know that in about 2/3 patients these fractures don’t come to immediate clinical attention.  We need to go out and look for those patients who are good candidates for TYMLOS therapy first-line. The AACE guidelines are very much in line with the patient population that we chose for the active trial and for use of TYMLOS.”

Dr. Cosman is concerned that more than 75% of high-risk post-menopausal women across the country are not being treated for osteoporosis, despite their potential for fractures, deformity, and disability.

“I am really happy that we have another tool in our armamentarium. We think this can really make a difference in the course of osteoporosis for postmenopausal women," Dr. Cosman said.

From the Trenches, a Clinical Perspective

"Abaloparatide is a daily injection like teriparatide.  Some of my patients want to abruptly end the discussion of these medications when I explain how to administer them while others automatically associate injections with flu shots, etc.," Dorothy A. Fink, MD, assistant attending physician at the Hospital for Special Surgery in New York City told EndocrineWeb.

I have found it helpful for patients to see an actual pen in order to understand how small the needle really is, said Dr. Fink, This surprises them as does how there is not nearly as much pain when the injection is given as they expected.

"Another challenge that occurs when we go through their osteoporosis history—patients tell me that they stopped the teriparatide after 2 years, and never followed up for treatment with anti-resorptive therapy.  This same issue will arise with abaloparatide since it is essential to treat with antiresorptive therapy after 2 years of abaloparatide," Dr. Fink told EndocrineWeb, "Reminding patients of the long-term treatment plan at every follow-up, or even considering a written out plan/contract, has been helpful in my practice."

Many patients associate osteoporosis only with women so men need to understand their fracture risk as well. "Even though men were not included in the ACTIVE study, we have to acknowledge that future studies will likely show benefit for men with severe osteoporosis just as they did with teriparatide," said Dr. Fink.  

Continue Reading:
Glucocorticoid-Induced Osteoporosis Management: New Guidelines
close X