dm+d

38186711000001103

New Medicines

EvenityOsteoporosis in men

Information

Evenity
New molecular entity
UCB Pharma
Amgen

Development and Regulatory status

Not recommended for approval (Negative opinion)
Not recommended for approval (Negative opinion)
Phase III Clinical Trials
Oct 19The revised indication now recommended for approval specifies post-menopausal women only [11].
Jul 19UCB have requested a re-examination of the CHMP recommendation. They have 60 days to submit their grounds for re-examination: CHMP will then re-examine the opinion within 60 days of receiving them. The company is not allowed to submit new scientific data but may request that a Scientific Advisory Group be consulted [28].
Jun 19Not recommended for EU approval - CHMP has adopted a negative opinion recommending the refusal of a marketing authorisation for romosozumab, because of concern that the trial results suggested an increased risk of serious effects on the heart or circulatory system; additionally, there were more deaths in patients over 75 given the medicine. As there was no clear mechanism for the adverse effects, and no clear patient group with a lower risk, measures to reduce the risk could not readily be put in place. Results showed a reduction in fracture risk in patients with severe osteoporosis, however results in less severe disease were less convincing. Under the circumstances, the drug´s benefits were not considered to outweigh its risks. The company has 15 days to request a re-examination of the opinion [9].
Jan 19UCB reports that the EU CHMP has issued a positive opinion [8].
Jan 18Amgen and UCB announced that the EMA has accepted the Marketing Authorization Application (MAA) for EVENITY™* (romosozumab) for the treatment of osteoporosis in postmenopausal women and in men at increased risk of fracture [7].
Jul 17The Complete Response Letter issued by the FDA in response to the filing for use in postmenopausal women asks for new safety and efficacy data from the PIII active-comparator ARCH study to be integrated into the drug’s submission, to build on that included in the original filing taken from the Phase III placebo-controlled FRAME study. The resubmission will also include efficacy and safety data from the BRIDGE study assessing romosozumab in men with osteoporosis [6].
Nov 15PIII study is ongoing [2].
Jun 14PIII study started Jun 14 [1].

Category

Humanized monoclonal antibody that inhibits sclerostin
The incidence rate of osteoporotic fractures in men aged 50-54 years is 0.67-0.72 per 1,000, rising to 4.35-5.08 per 1,000 in those aged 75-85 years (BMJ 2009;339:b4229)
Osteoporosis in men
Subcutaneous

Further information

Yes

Trial or other data

Nov 16Amgen report that PIII BRIDGE study (n=245) (NCT02186171) achieved primary outcome of statistically significant increase (12.1%; p<0.01) in BMD at the lumbar spine vs placebo at 12 months [5].
Mar 16Amgen and UCB announce positive top-line results for romosozumab from the pivotal Phase 3 placeBo-contRolled study evaluatIng the efficacy anD safety of romosozumab in treatinG mEn with osteoporosis (BRIDGE). These data showed the BRIDGE study met the primary endpoint, demonstrating a statistically significant increase in BMD) at the lumbar spine in 245 men with osteoporosis treated with romosozumab 210mg sc monthly vs. placebo at 12 months. All secondary endpoints comparing romosozumab with placebo were also met. Patients receiving romosozumab experienced a statistically significant increase in BMD at the femoral neck and total hip at 12 months and a statistically significant increase in BMD at the lumbar spine, femoral neck, and total hip at six months, compared with those receiving placebo. Overall patient incidence of adverse events and serious adverse events (SAEs) was generally balanced between arms. The most frequently reported adverse events (greater than 5% in the romosozumab arm) were nasopharyngitis, back pain, hypertension, headache and constipation. Injection site reactions were reported in 5.5% of patients in the romosozumab treatment group and 3.7% in the placebo group during the 12-month period. Most injection site reactions were reported as mild in severity. The patient incidence of positively adjudicated cardiovascular (CV) SAEs was 4.9% in the romosozumab group and 2.5% in the placebo group. The patient incidence of positively adjudicated CV death was 0.6% in the romosozumab group and 1.2% in the placebo group [4].
Jun 14NCT02186171 A PIII multicentre, randomized, double-blind study of romosozumab vs placebo in 225 men with osteoporosis. The primary outcome is percent change in bone mineral density (BMD) at the lumbar spine as assessed by dual-energy x-ray abosorptiometry (DXA) at 12 months. The study started in Jun 14 and is due to complete Dec 16 (primary data collection Jun 16) [1].

Evidence based evaluations