romosozumab Archives - The Antibody Society

Romosozumab-aqqg granted FDA approval

April 10, 2019 by Janice Reichert

On April 9, 2019, the US Food and Drug Administration approved romosozumab-aqqg (Evenity) to treat osteoporosis in postmenopausal women at high risk of bone fractures. Developed by Amgen and UCB, romosozumab is a humanized IgG2 monoclonal antibody that targets sclerostin. This is the second global approval of romosozumab, following its approval in Japan.

FDA’s approval was based the results of the Phase 3 placebo-controlled FRAME and active-controlled ARCH studies. As reported by Amgen, treatment with EVENITY resulted in a significant reduction of new vertebral fracture at 12 months compared to placebo in the FRAME study. This significant reduction in fracture risk persisted through the second year in women who received EVENITY during the first year and transitioned to denosumab compared to those who transitioned from placebo to denosumab. In addition, EVENITY significantly increased bone mineral density (BMD) at the lumbar spine, total hip and femoral neck compared to placebo at 12 months. Following the transition from EVENITY to denosumab at month 12, BMD continued to increase through month 24.

In the ARCH study, treatment with EVENITY for 12 months followed by 12 months of alendronate significantly reduced the incidence of new vertebral fracture at 24 months. EVENITY followed by alendronate significantly reduced the risk of clinical fracture (defined as a composite of symptomatic vertebral fracture and nonvertebral fracture) after a median follow-up of 33 months. EVENITY significantly increased BMD at the lumbar spine, total hip and femoral neck at 12 months compared to alendronate. Twelve months of treatment with EVENITY followed by 12 months of treatment with alendronate significantly increased BMD compared with alendronate alone.

The European Medicines Agency is reviewing a marketing application for romosozumab.

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The Antibody Society maintains a comprehensive table of approved mAb therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format. Information about other antibody therapeutics that may enter regulatory review in 2019 can be found in ‘Antibodies to watch in 2019’.

First approval for romosozumab

January 10, 2019 by Janice Reichert

Japan’s Ministry of Health, Labor and Welfare has granted a marketing authorization for romosozumab (EVENITY) for the treatment of osteoporosis in patients at high risk of fracture. Developed by Amgen and UCB, romosozumab is a humanized IgG2 monoclonal antibody that targets sclerostin. The approval in Japan is based on results from the Phase 3 FRAME and BRIDGE studies, which included 7,180 postmenopausal women with osteoporosis and 245 men with osteoporosis, respectively.

A biologics license application (BLA) for romosozumab as a treatment of osteoporosis in postmenopausal women at high risk for fracture was submitted to the U.S. Food and Drug Administration (FDA) in July 2016, but additional safety and efficacy data was requested in the FDA’s complete response letter, as announced by Amgen and UCB in July 2017. In July 2018, Amgen and UCB announced that the BLA had been resubmitted. In addition to data from early-stage clinical studies, the original BLA included data from the Phase 3 FRAME study. The resubmitted BLA includes results from the more recent Phase 3 ARCH study, an alendronate-active comparator trial including 4,093 postmenopausal women with osteoporosis who experienced a fracture, and the Phase 3 BRIDGE study. The FDA’s Bone, Reproductive and Urologic Drugs Advisory Committee is scheduled to review data supporting the BLA for romosozumab at a meeting on January 16, 2019.

The European Medicines Agency is also currently reviewing a marketing application for romosozumab.

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The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. Please log in to access the table, which is located in the Members Only section and can be downloaded in Excel format.

Updates on sarilumab, erenumab, romosozumab and XBiotech’s candidate antibody

May 25, 2017 by Janice Reichert

On May 22, 2017, the Food and Drug Administration (FDA) granted an approval for sarilumab (Kevzara) for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease modifying antirheumatic drugs, such as methotrexate (MTX). Sarilumab is a human monoclonal antibody (mAb) that targets interleukin-6 receptor (IL-6R), and has been shown to inhibit IL-6R-mediated signaling. Sarilumab was first approved on January 12, 2017 for the treatment of adult patients with moderately to severely active RA by Health Canada.

On May 18, 2017, Amgen announced that a biologics license application (BLA) for erenumab was submitted to the FDA. Erenumab is a human mAb targeting calcitonin gene-related peptide receptor. The BLA includes data from pivotal studies investigating the efficacy of erenumab versus placebo in reducing the number of migraine days for patients with episodic and chronic migraine.

On May 21, 2017, Amgen and UCB announced that the Phase 3 ARCH (Active-contRolled FraCture Study in Postmenopausal Women with Osteoporosis at High Risk of Fracture) study of romosozumab in postmenopausal women with osteoporosis at high risk for fracture based on previous fracture history met both primary endpoints and the key secondary endpoint. At the primary analysis, treatment with romosozumab for 12 months followed by alendronate significantly reduced the incidence of new vertebral fractures through 24 months, clinical fractures (primary endpoints) and non-vertebral fractures (key secondary endpoint) in postmenopausal women with osteoporosis at high risk for fracture, compared to alendronate alone. An imbalance in positively adjudicated cardiovascular serious adverse events was observed as a new safety signal (2.5% romosozumab vs 1.9% alendronate at 12 months). Overall adverse events and serious adverse events were generally similar between the treatment groups throughout the ARCH study and also in the initial 12-month romosozumab treatment period. No imbalance in cardiovascular serious adverse events was seen in the 7,180-patient placebo-controlled FRAME (FRActure study in postmenopausal woMen with ostEoporosis) study. Regulatory submissions for romosozumab based on the FRAME study results are currently under review with the FDA, Health Canada and the Pharmaceuticals and Medical Devices Agency in Japan. Amgen has agreed with the FDA that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization, and as a result Amgen does not expect approval of romosozumab in the US to occur in 2017. Amgen has indicated that engagement with PMDA and Health Canada will occur as part of the ongoing review process, and preparation for the European regulatory submission will continue as planned.

On May 18, 2017, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorization for human IgG1 monoclonal antibody specific for human interleukin-1 alpha XBiotech, intended for treating debilitating symptoms of advanced colorectal cancer. CHMP opinion was based on data from a study in 333 patients that evaluated the effects of the mAb vs placebo on lean body mass and quality of life. The committee noted that the study did not show clear improvements in either lean body mass or quality of life, and there was an increased risk of infection in patients taking the medicine, which was not considered acceptable in vulnerable patients who will be receiving palliative care. There were also inadequate controls of the manufacturing process to ensure the medicine would have the same quality as the product used in clinical trials. Therefore, the CHMP was of the opinion that the benefits of this medicine did not outweigh its risks. The EMA marketing authorization application procedure includes an appeal process. XBiotech Inc. has indicated that they may seek access to this process at the appropriate time.

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Update on antibodies in regulatory review

July 25, 2016 by Janice Reichert

A biologics license application (BLA) for romosozumab, an IgG2 monoclonal antibody targeting sclerostin, was recently submitted to the US Food and Drug Administration (FDA). The application includes data from the randomized, double-blind, placebo-controlled Phase 3 FRAME study (NCT01575834) of ~7,200 postmenopausal women with osteoporosis, defined as low bone mineral density at the total hip or femoral neck. The study met the primary endpoint of reduction of the incidence of new vertebral fracture through 12 months in postmenopausal women with osteoporosis treated with romosozumab. The study also evaluated whether romosozumab treatment for 12 months followed by denosumab (Prolia®) treatment for 12 months, compared with placebo followed by denosumab treatment, reduced the risk of new vertebral fractures through 24 months; this endpoint was also met. The effects of romosozumab were compared to teriparatide (FORTEO®), a recombinant form of parathyroid hormone, in the randomized, open-label Phase 3 STRUCTURE study (NCT01796301). In this study, postmenopausal women with osteoporosis transitioning from bisphosphonate treatment who were administered romosozumab demonstrated a statistically significant increase in hip bone mineral density and strength compared with those who received teriparatide.

In other news, the FDA requested the submission of new data and analyses from the MODIFY I (NCT01241552) and MODIFY II (NCT01513239) clinical trials of bezlotoxumab, which has extended the review time on bezlotoxumab by three months, to October 23, 2016. Bezlotoxumab, a human IgG1 mAb that targets Clostridium difficile (C. difficile) toxin B, was evaluated for prevention of C. difficile infection recurrence. MODIFY I was a Phase 3, randomized, double-blind, placebo-controlled, adaptive design study of a single infusion of bezlotoxumab, an anti-C. difficile toxin A human monoclonal antibody (MK-3415, and the combination of bezlotoxumab + MK-3415 in patients receiving antibiotic therapy for C. difficile infection. The Phase 3 MODIFY II study compared only bezlotoxumab and the combination of bezlotoxumab + MK-3415 to placebo in patients receiving antibiotic therapy for C. difficile infection. The primary endpoint, the rate of C. difficile infection recurrence through week 12 compared to placebo, was met in both studies.

The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the European Union and United States. Of the 8 mAbs currently in regulatory review in these regions, 4 have FDA action dates known to occur in late October-December 2016. One additional mAb is likely to have an FDA action date by the end of 2016, based on the date of BLA submission and review status. Please log in to access the table, located in the Members Only section.

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