Turbulent Path to Approval: Romosozumab (Evenity), the World’s First Anti-Sclerostin Monoclonal Antibody, Gains FDA Approval

On April 9, 2019, Amgen/UCB announced that the FDA had approved the sclerostin monoclonal antibody Evenity (romosozumab) for marketing, with an indication for osteoporosis in postmenopausal women at high risk of fracture. Evenity became the first anti-sclerostin monoclonal antibody drug approved globally, capable of both accelerating bone formation and reducing bone resorption. This article primarily focuses on the registration clinical data of Evenity (romosozumab) and provides a brief summary of currently noteworthy anti-sclerostin antibody products.

I. A Tortuous Review Path:

Evenity (romosozumab) Finally Approved in the United States

On January 8, 2019, Amgen/UCB announced that Japan’s Ministry of Health, Labour and Welfare had granted the world’s first approval for the marketing of the sclerostin monoclonal antibody Evenity (romosozumab), marking a significant milestone for this drug.

On April 9, 2019, Evenity (romosozumab) was finally approved in the United States, marking the end of a 2-year and 9-month review process.

In fact, on July 21, 2016, Amgen/UCB submitted a marketing application for Evenity (romosozumab) to the FDA; this application was primarily based on data from the FRAME (NCT01575834) clinical trial;

On July 16, 2017, the FDA issued a Complete Response Letter requiring Amgen/UCB to submit updated clinical trial data from the ARCH study (NCT01631214).

On July 12, 2018, Amgen/UCB submitted the second marketing application for Evenity (romosozumab) to the FDA.

Key Milestones in the Regulatory Review for Evenity (romosozumab) Market Approval:

The FRAME and ARCH trials were the pivotal clinical studies supporting the market approval of Evenity (romosozumab).

FRAME and ARCH clinical trials confirmed that romosozumab provides clear clinical benefits for postmenopausal women with osteoporosis, reducing the risk of fractures while increasing bone mineral density at the lumbar spine, hip, and femoral neck.

For detailed clinical trial data, please refer to the primary data of the registered clinical trials below and consult relevant literature.

Following its initial approval in the United States, romosozumab reached a significant milestone; the drug also carries a black box warning:

Romosozumab carries a potential risk of increasing the incidence of myocardial infarction, stroke, and cardiovascular death; physicians should weigh the benefit-risk ratio of romosozumab in patients with concomitant cardiovascular disease.

II. Anti-sclerostin Antibody

Romosozumab became the world’s first anti-sclerostin antibody.

Introduction to Romosozumab:

Reference: Profile of romosozumab and its potential in the management of osteoporosis

Romosozumab is a humanized monoclonal antibody targeting sclerostin. By binding to sclerostin, romosozumab blocks the sclerostin-LRP-5/6 pathway, thereby accelerating bone formation and reducing bone resorption.

In addition to romosozumab, Eli Lilly’s LY2541546 and Mereo BioPharma’s setrusumab are in clinical development and represent two noteworthy candidates currently in the clinical stage.

There are few domestic companies developing anti-sclerostin antibodies; currently, HengruiPharmaceuticalsSHR-1222 Enters Phase I Clinical Trials; SHR-1222 Is a Leading Anti-Sclerostin Antibody Product Developed in China.

Major anti-sclerostin antibodies:

III. A Large Global Population at Risk of Fractures

Data show that nearly one-third of women and one-fifth of men worldwide are at risk of osteoporotic fractures. A report by the International Osteoporosis Foundation indicates that bone mineral density in the human body declines significantly with age, leading to an increased risk of fractures.

Source: International Osteoporosis Foundation

Appendix: Key Data from the Registered Clinical Trial

FRAME，NCT01575834

FRAME: An international, multicenter, randomized, placebo-controlled Phase 3 clinical trial enrolling 7,180 postmenopausal women with osteoporosis to evaluate the safety and efficacy of romosozumab.

FRAME Clinical Data:

ARCH，NCT01631214

The ARCH trial recruited 4,093 postmenopausal women with osteoporosis for an international, multicenter, randomized, alendronate-controlled Phase 3 clinical trial to evaluate the safety and efficacy of romosozumab versus alendronate in patients with osteoporosis.

Other Data:

The BRIDGE study also confirmed that romosozumab has a favorable safety and tolerability profile, while increasing the areal bone mineral density (aBMD) at the lumbar spine, total hip, and femoral neck in men with osteoporosis.

BRIDGE，NCT02186171

The BRIDGE Study Enrolled 245 Male Patients with Osteoporosis: A Multicenter, Randomized, Placebo-Controlled Phase 3 Clinical Evaluation

Source: CPhI Pharma Online Author: 1°C