Type of information: Refusal of a Market Autorisation in the EU
Product name: Eladynos®/Tymlos®
Therapeutic area: Bone diseases
- peptide. Abaloparatide-SC is a novel 34–amino acid peptide similar to part of the human parathyroid hormone. It has been created to be a potent and selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway. It stimulates bone formation by acting on osteoblasts.
Company: Radius Health (USA - MA)
Disease: postmenopausal women with osteoporosis at high risk for fracture
- • On July 26, 2018, the Committee for Medicinal Products for Human Use (CHMP) confirmed the refusal of the marketing authorisation of Eladynos® intended for the treatment of osteoporosis. Radius International has requested a re-examination of the initial opinion. After considering the grounds for this request, the CHMP re-examined the opinion, and confirmed the refusal of the marketing authorisation.
- • On March 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative
opinion, recommending the refusal of the marketing authorisation for Eladynos®, intended for the treatment of osteoporosis. Radius Health presented the results of one main study in women who had been through the menopause and who were at risk of fractures. Women received Eladynos or teriparatide or placebo for 18 months. Measures of
effectiveness were the number of new vertebral fractures and the number of non-vertebral fractures (including hip fractures, which can be serious and disabling). The CHMP considered that the main study did not satisfactorily show that Eladynos® is effective at preventing non-vertebral fractures in women who have been through the menopause.
The data from two of the study sites were not reliable and had to be excluded as the study had not been conducted in compliance with ‘good clinical practice’ (GCP) at those sites.
From a safety point of view, the CHMP was concerned about the medicine’s effects on the heart, such as increases in heart rate and palpitations. Because most post-menopausal women are at an increased risk of heart problems, the CHMP could not identify a group of patients in whom the benefits would outweigh the risks. Therefore, the committee recommended that the medicine be refused marketing authorisation.
- • On July 21, 2017, Radius Health announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), issued a second Day-180 List of Outstanding Issues and requested additional data analyses related to the safety and efficacy of abaloparatide-SC in the process of their ongoing regulatory review. Radius expects the CHMP to issue an opinion regarding the MAA for abaloparatide-SC prior to the end of 2017.
- If approved, abaloparatide-SC will be marketed in the European Union as Eladynos® and would be the first new anabolic approved in Europe in 14 years.
- • On April 28, 2017, Radius Health announced that the FDA has approved Tymlos® (abaloparatide) injection 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. The FDA's approval of Tymlos® was based on results at 18 months from the landmark ACTIVE trial and first six months of ACTIVExtend trial that demonstrated consistent significant and rapid reductions in the risk of vertebral and nonvertebral fractures regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral) and bone mineral density (BMD) at baseline. In human clinical studies, Tymlos® has been shown to decrease the incidence of new vertebral and nonvertebral fractures, to increase bone mineral density (BMD), and to increase a marker of bone formation. In addition, the anabolic effect of Tymlos® was demonstrated in animal studies by increases in BMD and bone mineral content that correlated with increases in bone strength at vertebral and/or nonvertebral sites. Specifically, in the ACTIVE trial, Tymlos® demonstrated significant reductions in the relative risk of new vertebral and nonvertebral fractures compared to placebo in the ACTIVE trial of:
- - 86% in new vertebral fractures
- - 43% in nonvertebral fractures
The absolute risk reductions were 3.6% and 2.0%,respectively.
- • On May 31, 2016, Radius Health announced that its New Drug Application (NDA) for abaloparatide—SC has been accepted for filing by the FDA. The NDA is supported by data from the entire abaloparatide-SC development program, including the results from the 18-month Phase 3 ACTIVE trial in 2,463 postmenopausal women with osteoporosis and the first six months of the ACTIVExtend trial in 1,139 of the ACTIVE participants.
- Radius submitted a Centralised Marketing Authorisation Application (MAA) for abaloparatide-SC in the European Union on November 17, 2015, which was validated by the European Medicines Agency (EMA) in December 2015, and is currently undergoing active regulatory assessment by the Committee for Medicinal Products for Human Use of the EMA (CHMP). The EMA has granted Radius an additional 3-month extension to the procedural timetable for response in the ongoing MAA assessment. As a result of this extension to the procedural timetable, the company now anticipates that the CHMP may adopt an Opinion regarding the MAA in late 2016 or in 2017.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE: 2015-11-17
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-04-28
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: