Reimbursement Recommendation

Romosozumab (Evenity)

Indication: The treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture

Request for advice: From public drug programs

Updated reimbursement recommendation: Reimburse with conditions

This recommendation supersedes the CADTH Canadian Drug Expert Committee recommendation for this drug and indication dated November 29, 2021.

On July 16, 2026, the Formulary Management Expert Committee (FMEC) deliberated on a Request for Advice for the past romosozumab reimbursement recommendation for the treatment of osteoporosis.

What Is a Request for Advice?

As described in the Procedures for Reimbursement Reviews, the Request for Advice process is applied when public drug programs request clarification on conditions and/or criteria to an existing reimbursement recommendation in light of contextual or practice changes that impact the ability of drug programs to implement an existing reimbursement recommendation.

In this case, public drug plans were seeking clarification on the definition, interpretation, and/or meaning of “treatment naive” that should be applied for reimbursement of romosozumab, as outlined in the reimbursement conditions from the Canadian Drug Expert Committee (CDEC) in 2021.

What Are the Updated Conditions for Reimbursement?

FMEC recommends updating the initiation condition for the reimbursement of romosozumab, such that reimbursement would no longer be contingent upon the need for a patient to be “treatment naive.”

Why Did Canada’s Drug Agency Make This Updated Recommendation?

In keeping with the current policy and procedures for a Request for Advice, FMEC’s review was limited to clinical trials considered as part of the 2021 CDEC reimbursement review of romosozumab. FMEC reviewed a report prepared by Canada’s Drug Agency (CDA-AMC) that summarized the inclusion and exclusion criteria of clinical trials evaluated as part of the 2021 review, exposure-response data related to antiosteoporotic treatments, guidance outlined in Canadian and international clinical guidelines and health technology assessments for treatment with romosozumab for osteoporosis, utilization data from 2019 to 2025, and input from interested parties, including 1 patient group, industry, 8 clinician groups, and 4 clinical experts.

FMEC deliberated on a definition for “treatment naive;” however, was unable to develop an evidence-based definition. After reviewing the evidence in the CDA-AMC report, FMEC concluded that there is no standardized definition of “treatment naïve” based on the clinical trials, nor within clinical practice based on expert opinion or outlined by Canadian or international guidelines. FMEC also considered exposure-response data; however, agreed that due to variation in the duration of effectiveness after discontinuation of antiosteoporotic treatments this data also did not support development of criteria for a patient to be considered “treatment naive.”

Review Background

What Is Osteoporosis?

Osteoporosis is a bone disease characterized by low bone mass, weakened bone strength, and decreased bone quality, which results in an increased risk of fracture. Hip, vertebral, pelvic, and femur fractures are also associated with increased mortality risk. Osteoporosis affects 2.3 million people in Canada and is most predominant in individuals in postmenopause.

What Are the Current Treatment Options?

Current pharmacologic treatment options for osteoporosis include antiresorptive and anabolic drugs. Antiresorptive drugs, such as bisphosphonates, denosumab, and selective estrogen receptor modulators slow bone loss by inhibiting osteoclasts that breakdown existing bone tissue. Anabolic drugs, such as teriparatide and romosozumab actively build new bone by stimulating osteoblasts.

What is Romosozumab?

Romosozumab has a Health Canada indication for “the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture.” Romosozumab is a humanized monoclonal antibody that inhibits the action of sclerostin, a major endogenous suppressor of osteoblasts. Additionally, sclerostin inhibition by romosozumab reduces osteoclastic bone resorption. The clinical effect of romosozumab is both anabolic and anticatabolic, leading to rapid antifracture efficacy. Romosozumab is available as a solution for subcutaneous injection in a prefilled syringe, 105 mg/1.17 mL, and the Health Canada–approved dose is 210 mg administered once every month. Treatment duration of romosozumab is limited to 12 months.

Why Did We Conduct This Review?

In 2021, CDEC recommended that romosozumab be reimbursed if conditions were met, of which 1 of the conditions required that patients must be “treatment naive” to osteoporosis medications (with the exception of calcium and/or vitamin D). Public drug programs requested clarification, a definition, and/or advice on interpretation of the reimbursement condition requiring patients to be “treatment-naive” and how it should be applied in the context of osteoporosis and in light of the following unmet needs:

• Patients who were intolerant to 1 or more osteoporosis treatments following a short course of therapy.

• Patients who were initiated on a prior osteoporosis treatment but romosozumab is the recommended treatment following subsequent evaluation (e.g., following specialist consultation or identification of contraindication[s] to the initial treatment).

• Patients with remote prior exposure to antiresorptive therapy (e.g., following a bisphosphonate drug holiday) who require reinitiation of therapy, and for whom romosozumab is the preferred option.

Public drug plans noted that prescriptive timelines to deem a patient “clinically treatment naive” could place patients at increased risk of fracture should they discontinue treatment with another osteoporosis therapy to meet “clinically treatment naive” timelines.

Highlights of Input from Interested Parties

• One patient group, Osteoporosis Canada, submitted input for this review. Osteoporosis Canada noted the impact of fragility fractures can be substantial and is associated with acute and often chronic pain, decreased independence and mobility, social isolation resulting in depression, institutionalization, and even death. Osteoporosis Canada felt the undefined condition of “treatment naive” has led to variation in access to romosozumab for patients at high risk of fracture who have had any prior exposure to osteoporosis medications, such as bisphosphonates due to varying interpretation and application of “treatment naive.”

• Eight clinician groups, BC Coalition of Osteoporosis Physicians, Canadian Geriatrics Society, The Canadian Society of Endocrinology and Metabolism, Osteoporosis Canada Scientific Advisory Council, British Columbia Society of Rheumatologists, Fragility Fracture Network, Canadian Endocrine Update, and Canadian Rheumatology Association submitted input for this review. Clinician groups felt that clinical confusion exists regarding the meaning of “clinically treatment naive” which they felt is to the detriment of patients. Clinician groups felt that a consistent, reasonable, and evidence-based definition of “clinically treatment naive” would lead to increased uniformity and fair access to romosozumab reimbursement.

Person With Lived Experience

A person with lived experience from Quebec shared her treatment journey with osteoporosis. She was first diagnosed with osteopenia, followed by a diagnosis of osteoporosis in 2009. She was started on treatment with risedronate (a bisphosphonate), which was then switched to denosumab in 2017. She was followed by her endocrinologist twice a year for blood tests and administration of her denosumab. In March 2021, she experienced a fall and fractured the neck of her femur. In September 2021 upon a subsequent referral and review with another endocrinologist, she started treatment with romosozumab to prevent future fractures. Her treatment consisted of monthly injections for 1 year. She reported that her transition to romosozumab was without issues and was well tolerated. She experienced an increase of bone mass with no osteoporosis-related fractures since then. After completing a 1-year course of romosozumab, she restarted treatment with denosumab. She continues to lead an active life. She was fortunate to have her treatment covered by the Quebec Health Insurance Plan and bore no additional cost of treatment.

Disclaimer: The perspectives shared by people with lived experiences who present to the committee reflect their individual experiences and are not necessarily representative of all people with the same condition or course of treatment. Their insights provide valuable context about what a patient, support person, or caregiver might go through when facing this condition or treatment, helping to inform the committee’s deliberations. These narratives complement other forms of evidence and input and should be considered as part of a broader understanding of the condition and treatment under review. When gender or gendered pronouns are used in these narratives, they are included with the permission of the individual.

Recommendation

In the context of this Request for Advice on the 2021 CDEC recommendation, FMEC considered the following policy question:

What are the clinical criteria, specific to previous use of osteoporosis medications, for treatment with romosozumab in patients with osteoporosis at high risk for fractures?

With a vote of 9 to 0, FMEC voted to remove the condition for patients to be “treatment naive.” FMEC agreed upon updating the condition as outlined in Table 1.

Table 1: Reimbursement Conditions, Reasons, and Guidance

BMD = bone mineral density; CDA-AMC = Canada’s Drug Agency; CDEC = Canadian Drug Expert Committee; FMEC = Formulary Management Expert Committee; HTA = health technology assessment; ICER = incremental cost-effectiveness ratio; ITC = indirect treatment comparison; QALY = quality-adjusted life-year.

Summary of Deliberation

FMEC deliberated on the following 4 domains of value of the deliberative framework before developing their recommendations: clinical value, unmet clinical need, distinct social and ethical considerations, and impacts on health systems. Economic considerations were not evaluated as part of the Request for Advice. For further information on the domains of value, please refer to the Expert Committee Deliberation at Canada’s Drug Agency document.

FMEC considered the following key discussion points, organized by the following domains of value.

Clinical Value

• FMEC concluded that romosozumab demonstrates acceptable clinical value versus appropriate comparators within the treatment landscape in Canada.

• Through reflection on the input from the patient group or insights shared by people with lived experience, FMEC members noted the following important patient values or perspectives:

  • The impact of fragility fractures can be substantial and is associated with acute and chronic pain, decreased independence and mobility, and social isolation resulting in depression, institutionalization, and even death.

• FMEC members highlighted the following discussion points:

  • The clinical efficacy of romosozumab was previously evaluated as part of the November 2021 CDEC review. At that time, CDEC concluded that romosozumab provided acceptable clinical value based on evidence from the ARCH trial. CDEC also noted that romosozumab may address some of the needs that are important to patients, including reducing the risk of osteoporosis-related fractures. CDEC acknowledged that up to 10% of patients enrolled in the ARCH and FRAME trials were “treatment experienced.”

  • The studied comparators align with clinical practice in Canada. Other commonly used osteoporosis treatments were not included as comparators in the studies such as denosumab, zoledronic acid, risedronate, and selective estrogen receptor modulators.

  • The STRUCTURE trial was submitted by the sponsor as part of the 2021 CDEC review. However, teriparatide was not included as a comparator in the 2021 systematic review, and therefore STRUCTURE was not included in the 2021 clinical evaluation. Given that teriparatide may be reimbursed by some public drug programs, FMEC reviewed the inclusion and exclusion criteria and primary findings of the STRUCTURE trial to assess whether romosozumab is effective in patients with prior bisphosphonate exposure.

  • The STRUCTURE trial, which evaluated the effectiveness of romosozumab compared to teriparatide in patients with treatment experience with recent bisphosphonate use, romosozumab demonstrated a 2.6% improvement in total hip areal bone mineral density, which was deemed clinically important by the clinical experts consulted who also confirmed that bone mineral density is a reliable surrogate end point.

  • FMEC agrees with the previous assessment by CDEC and acknowledges there is uncertainty in the evidence relating to patients with treatment experience in the ARCH and FRAME trials, which was highlighted by CDEC in 2021 due to the small number of patients with treatment experience. Although up to 10% of patients in the ARCH and FRAME trials had prior use of osteoporosis treatments, it is unknown how many patients had prior exposure to other osteoporosis treatments beyond the inclusion criteria threshold (i.e., ≥ 5 years before enrolment).

  • Clinical guidelines developed since the 2021 CDEC recommendation, including the 2023 Canadian guidelines do not address or define “clinically treatment naive.” Clinical experts confirmed that no definition exists regarding “clinically treatment naive” in the treatment of osteoporosis in Canada and acknowledge there are variations in efficacy and persistence of osteoporosis treatments as they relate to fracture risk reduction.

  • Variations exist in absorption, onset of action, half-life, and clearance of different available treatment options. There are also variations in the known efficacy of osteoporosis treatments as it relates to fracture risk reduction, and how long those effects persist after discontinuing treatment.

Unmet Clinical Need

• FMEC concluded that there is significant clinical need arising from osteoporosis despite available treatments.

• Through reflection on the input from patient groups or insights shared by people with lived experience, FMEC members noted the following important patient values or perspectives:

  • The patient group identified unmet clinical needs in patients experiencing vulnerability with an increased risk of fracture who cannot access effective treatment options due to access-related barriers. The patient group shared that access-related barriers diminish longevity and quality of life for these patients and are costly to health care systems.

  • Patient and clinician groups noted the undefined condition of “treatment naive” in the 2021 CDA-AMC romosozumab reimbursement condition led to confusion regarding treatment availability and variation across the country, and treatment gaps in patients at high risk of fracture.

  • Patient groups noted the importance of choice of alternate treatment options to preserve health-related quality of life and prevent fracture-related deaths.

• FMEC members highlighted the following discussion points:

  • Fractures are associated with significant morbidity, loss of function, pain, and decreased health-related quality of life. Clinical experts underscored the health-related quality of life and mortality risks associated with fractures, and the importance of alternative treatment options.

  • Clinical experts discussed limited treatment choices and unmet need in patients who received prior remote exposure to an osteoporosis treatment or were recently started on a treatment option that they are unable to tolerate.

  • FMEC noted that alternative treatments are available for osteoporosis. However, the only other anabolic drug, teriparatide, is not publicly reimbursed across all jurisdictions and is a 2-year daily injection rather than a 1-year monthly injection.

Distinct Social and Ethical Considerations

• FMEC concluded that updating the romosozumab reimbursement condition to include patients with osteoporosis regardless of prior treatment exposure would address a significant nonclinical need arising from osteoporosis despite available treatments.

• Through reflection on the input from the patient group or insights shared by people with lived experience, FMEC members noted the following important patient values or perspectives:

  • The patient group expressed the importance of having a choice of alternative treatment options to prevent osteoporosis-related fractures. They noted the importance of an effective treatment that prevents osteoporosis-related fractures, is easily administered, and well tolerated by patients.

• FMEC members highlighted the following discussion points:

  • FMEC acknowledged the ethical concerns raised by clinician groups and public drug programs regarding potential unintended impact on patient care should a prescriptive definition of “clinically treatment naive” with specific washout periods and timelines be recommended, which may result in inappropriate discontinuation or withholding treatment to meet eligibility criteria.

  • The only other anabolic treatment option is a daily injection of teriparatide for 2 years, which is a treatment burden on patients and their caregivers, particularly in older individuals. Romosozumab addresses this unmet nonclinical need by reducing the burden from daily to monthly injections when compared to teriparatide over a shorter course of treatment.

  • Based on the drug utilization data, which evaluated romosozumab use regardless of prior exposure to other osteoporosis drugs, a higher proportion of individuals eligible for age-related coverage (65 years and older) received romosozumab through private insurance coverage or self-pay, which may reflect challenges accessing treatment through public plans and potential inequities in access.

  • Based on the drug utilization data, an association was observed between higher income and receipt of romosozumab, suggesting a potential equity-related signal.

Economic Considerations

• FMEC did not deliberate upon economic considerations as part of the Request for Advice deliberations as the CDA-AMC report did not include economic factors. The anticipated change in the population eligible to receive romosozumab may have impacts on its relative cost-effectiveness and budget impact that could not be reflected in this updated recommendation.

• Feasibility of adoption: Drug programs may wish to consider budget impact implications associated with the updated condition for reimbursement to assess and inform implementation considerations.

Impacts on Health Systems

• FMEC concluded that broader access to romosozumab may alleviate the impacts of osteoporosis on health systems.

• Through reflection on the input from patient groups or insights shared by people with lived experience, FMEC members noted the following important patient values or perspectives:

  • The patient group noted that clarity around the condition of “treatment naive” is needed to support equitable implementation.

• FMEC members highlighted the following discussion points:

  • Amending the requirement for patients to be “treatment naive" may alleviate challenges regarding acute care access and home care, with expected fracture risk reduction.

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project webpage):

• the CDA-AMC romosozumab Request for Advice report (refer to the Main Report)

• patients' perspectives gathered by 1 patient group, Osteoporosis Canada (refer to the Patient and Clinician Group Input document)

• industries’ perspectives gathered by 1 industry group, Amgen (refer to the Industry Group input)

• input from a person with lived experience who delivered a brief presentation (refer to the Person With Lived Experience section in this document)

• input from 8 clinician groups, BC Coalition of Osteoporosis Physicians, Canadian Geriatrics Society, The Canadian Society of Endocrinology and Metabolism, Osteoporosis Canada Scientific Advisory Council, British Columbia Society of Rheumatologists, Fragility Fracture Network, Canadian Endocrine Update, and Canadian Rheumatology Association (refer to the Patient and Clinician Group Input document)

• input from public drug programs that participate in the reimbursement review process

• input from 4 clinical experts with expertise in the management of osteoporosis consulted by CDA-AMC.

Feedback on Draft Recommendation

All feedback received in response to the draft recommendation is available on the CDA-AMC project webpage.

FMEC Information

Members of the committee: Dr. Emily Reynen (Chair), Dr. Zaina Albalawi, Ms. Marilyn Barrett, Dr. Hardit Khuman, Ms. Valerie McDonald, Dr. Bill Semchuk, Dr. Jim Silvius, Dr. Marianne Taylor, Dr. Maureen Trudeau, Dr. Dominika Wranik. Two guest specialists attended the FMEC deliberation from Newfoundland and Labrador and British Columbia participated in this review.

Meeting date: July 16, 2026

Conflicts of interest: None

CDEC Information

Members of the committee: Dr. James Silvius (Chair), Dr. Ahmed Bayoumi, Dr. Sally Bean, Dr. Bruce Carleton, Dr. Alun Edwards, Mr. Bob Gagne, Dr. Ran Goldman, Dr. Allan Grill, Mr. Allen Lefebvre, Dr. Kerry Mansell, Ms. Heather Neville, Dr. Danyaal Raza, Dr. Emily Reynen, Dr. Yvonne Shevchuk, and Dr. Adil Virani.

Meeting date: September 22, 2021

Conflicts of interest: None

Special thanks: CDA‑AMC extends special thanks to the individuals who presented directly to FMEC and to patient organizations representing and supporting the community of people living with osteoporosis.

Note: CDA‑AMC makes every attempt to engage with people with lived experiences as closely to the indication and treatments under review as possible; however, at times, CDA‑AMC is unable to do so and instead engages with individuals with similar treatment journeys or experience with comparators under review to ensure lived experience perspectives are included and considered in Reimbursement Reviews. CDA‑AMC is fortunate to be able to engage with individuals who are willing to share their treatment journey with FMEC.