Patients requiring bone anabolic therapy with romosozumab should be treatment naïve per recent studies. Provincial formularies' interpretation of "treatment naïve" has been quite variable. A scientifically valid definition of "clinically treatment naïve" has been explored.
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The U.S. Food and Drug Administration (FDA) has qualified image-based bone mineral density (BMD) biomarkers as a surrogate endpoint for fractures in clinical trials of osteoporosis therapies, marking an important advance in drug development. This milestone resulted from the Study to Advance BMD as a Regulatory Endpoint (SABRE), a multi-sector collaboration initiated by the American Society for Bone and Mineral Research (ASBMR) and the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium, and led by ASBMR experts Dennis Black, PhD, Mary Bouxsein, PhD, and Richard Eastell, MD. ASBMR provided financial and institutional support through sustained public–private partnerships, with ongoing leadership from multiple ASBMR Councils and presidents, most recently Drs. Peter Ebeling, Mary Bouxsein, Laura Calvi, and Jennifer Westendorf.
Historically, FDA approval of osteoporosis therapies has relied on fracture outcomes, which are relatively infrequent events and therefore require large, lengthy, and costly clinical trials, limiting innovation—particularly for novel or combination treatments. By qualifying image-based BMD as a surrogate endpoint, the FDA formally recognizes that BMD improvements reliably predict fracture risk reduction, enabling smaller and shorter trials, lowering development costs, accelerating patient access to new therapies (including anabolic and sequential approaches), and facilitating studies in high-risk or niche populations where fracture endpoints are impractical. Clinically, this decision validates long-standing practice that BMD is a meaningful marker of treatment benefit, and strategically, it aligns osteoporosis with other fields that use biologically sound surrogate endpoints to drive progress, with the potential to substantially reduce the current treatment gap.
To learn more, watch this video by ASBMR where Dr. Black and Dr. Bouxsein further discuss the impact of this decision.
Denosumab Biosimilar Initiative Switch – August 29, 2024 to March 3, 2025
Many are aware that PharmaCare has switched coverage (with Special Authority approval) from the originator biologics for denosumab (Prolia® and Xgeva®) to biosimilar versions (Jubbonti® for patients using Prolia, and Wyost™ for patients using Xgeva). Prescribers and Pharmacists are encouraged to educate and help patients understand the Prolia and Xgeva transition to an approved biosimilar during the six-month transition period from August 29, 2024 to March 3, 2025. Practitioners should provide balanced education and avoid the “nocebo effect” and answer questions in the best interest of the patient. If the patient would like to maintain PharmaCare coverage for Prolia or Xgeva, if started and approved before August 29, 2024, coverage will be maintained until March 3, 2025. After March 3, 2025, BC PharmaCare will only continue coverage for the biosimilar version, and the patient may need to pay out of pocket for the originator.
Private payers have followed suit with changes to their respective coverage to move from coverage of the originator to the biosimilar versions as well. Some patients may have premium private plans which will continue to cover the originator Prolia or Xgeva, and pharmacists can confirm coverage through submitting the claim or contacting the private payer, after March 3, 2025.
As of August 29, 2024, all new Special Authority (SA) requests, including SA renewals, for denosumab will only be approved for a biosimilar product (Jubbonti or Wyost). After March 3, 2025, Prolia and Xgeva become PharmaCare non-benefits and only Jubbonti or Wyost will be covered by PharmaCare if SA is approved. There is a potential for exceptional special access coverage for some patients provided that there is a strong rationale and need for the patient to receive coverage for the originator that is accepted by PharmaCare, but this will require the prescriber to submit a request for exceptional coverage and document the rationale and why the biosimilar is not suitable, but it is anticipated that approvals are rare.
Some patients with private plan coverage may receive a letter from their private payer informing the patient of the change in coverage, but not all patients may be informed this way. Pharmacists are encouraged to alert the patient of the upcoming changes and provide biosimilar education which is funded by BC PharmaCare for a one-time education session per patient completed before March 3, 2025. There is a billing code pharmacists may submit as well as one that is for physicians to submit (Biosimilar Initiative see: Biosimilars Initiative for patients - Province of British Columbia)
Patient support fees for pharmacists and prescribers (from PharmaCare)
Pharmacists can help identify patients who may be affected by the switch and let them know they need a new prescription to maintain coverage. In recognition of this support, a $15 patient support fee is offered to pharmacies for their efforts. The fee is submitted as a PIN (66128494) in PharmaNet. Only one patient support fee can be claimed per PHN, within the switch period window, ending March 3, 2025. This patient support fee can only be claimed for patients currently on the Prolia or Xgeva brands of denosumab prior to August 29, 2024, and who are covered by PharmaCare for either brand of denosumab.
See procedures for Pharmacists: https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/pharmacare/programs/biosimilars-initiative-health-professionals#pharmprocedure
The manufacturer for Prolia, Amgen, supports a program that provides patient access to financial reimbursement through MyRx Care ( https://myrx.care/). Pharmacists can enrol the patient in this program for support, but financial assistance is only available to patients who do not receive any BC PharmaCare coverage. The level of financial reimbursement is usually sufficient to cover the copay amount for private plans so the patient may not have to pay out of pocket, and for those without any coverage it can help provide some financial assistance to reduce the cost to the patient.
It is important for patient safety to ensure denosumab is not inadvertently discontinued without an alternative treatment used to prevent fractures since recent evidence has shown that patients previously treated with denosumab who discontinue the drug have an increased risk for vertebral fractures and may occur as soon as eight months after the last injection of the drug. Pharmacists are encouraged to follow-up on patients being treated with denosumab to ensure that their last dose has not been longer than 7 months ago.
Biologic and Biosimilar Prescriptions
It is important for Pharmacists in BC to note that biologics and biosimilars are not interchangeable and essentially both biologics and biosimilars are both Brand Name products. Biosimilars are not generics, which are interchangeable, and biosimilars undergo a more rigorous approval process with Health Canada requiring clinical trials in patients with the indicated condition. The generic product approval process does not require testing of the generic product in individuals with the condition and bioequivalence studies can be carried out in healthy volunteers only.
Therefore, if a Pharmacist receives a prescription stating Prolia, the prescription must be dispensed with Prolia unless the Pharmacist has a patient-centred reason exercising clinical judgement to adapt the prescription and substitute Jubbonti for Prolia. However, if the prescriber writes “denosumab”, the Pharmacist may exercise clinical judgment in the interest of the patient together with their preferences and may select either Prolia or Jubbonti (or other biosimilar denosumab on the market as they are introduced) as appropriate. Health Canada’s position is that it does not consider biosimilars to be the same as generic drugs and also considers biosimilars as non-interchangeable with the originator and also non-interchangeable with other biosimilar versions.
In a clarification question posed to the College of Pharmacists of BC, I was told “if a prescriber has not specified a specific brand of the molecule [adalimumab], then the pharmacist can select an option they believe is appropriate for the patient. [They] The Pharmacist would not need to contact the prescriber unless they are unsure about the choice or have a question for the prescriber. Further clarification received is that, if a patient has already been on a particular product and the pharmacist wants to switch them to a biosimilar product, then the two potential options they have are either a generic substitution or a therapeutic substitution (as an adaptation).”
Since each case may have other unique circumstances, Pharmacists are encouraged to exercise good clinical judgement and if needed contact the College of Pharmacists of BC for clarification around prescription regulations and interchangeability.
Prepared by: Alan Low, BSc.(Pharm.), Pharm D., RPh, ACPR, FCSHP, CCD