Galcanezumab (Emgality)

CADTH recommends that Emgality should be reimbursed by public drug plans for the prevention of migraine if certain conditions are met. Emgality should only be covered to prevent migraine attacks in adult patients who have tried at least 2 other types of oral preventive medications. Emgality should only be reimbursed if the patient is being cared for by a physician who has experience managing migraine headaches. Emgality will only be reimbursed for 6 months at a time. Emgality should not be more than the least costly drug of the same class used to prevent migraine.

Macitentan and Tadalafil (Opsynvi)

CADTH recommends that Opsynvi should be reimbursed by public drug plans for the long-term treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to reduce morbidity in patients in WHO functional class (FC) II or III whose PAH is idiopathic, heritable, or associated with connective tissue disease or congenital heart disease if certain conditions are met. Opsynvi should only be covered for patients who are currently treated simultaneously with stable doses of macitentan 10 mg and tadalafil 40 mg as separate tablets. Opsynvi should only be reimbursed if prescribed by a specialist with expertise in managing and treating patients with PAH and if the price of Opsynvi is negotiated to ensure cost savings in comparison with separate macitentan and tadalafil tablets.

Luspatercept (Reblozyl)

CADTH recommends that Reblozyl should be reimbursed by public drug plans for the treatment of adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS)-associated anemia who have ring sideroblasts and require red blood cell (RBC) transfusions, if certain conditions are met. Reblozyl should only be covered to treat patients who have failed or are not suitable for erythropoietin-based therapy. Reblozyl should only be reimbursed if prescribed by a specialist in MDS and if the cost of Reblozyl is reduced. Reimbursement should only be renewed if Reblozyl shows benefit to the patient such that the patient no longer requires RBC transfusions.

Pembrolizumab (Keytruda)

CADTH recommends that Keytruda should be reimbursed by public drug plans for the treatment of esophageal or human epidermal growth factor receptor 2 (HER2)-negative esophagogastric junction (EGJ) cancer that cannot be removed by surgery or is metastatic, if certain conditions are met. Keytruda should only be covered to treat adult patients who have not received previous treatment for advanced or metastatic esophageal or EGJ cancer and who have good performance status. Keytruda should only be reimbursed if prescribed in combination with platinum and fluoropyrimidine–based chemotherapy and given by a clinician who is experienced in treating cancer. The price of Keytruda must be lowered to be cost-effective and affordable.

Zanubrutinib (Brukinsa)

CADTH recommends that Brukinsa be reimbursed by public drug plans for the treatment of adult patients with relapsed or refractory Waldenström macroglobulinemia (WM), if certain conditions are met. Brukinsa should only be covered to treat patients with relapsed or refractory WM who have received at least 1 prior line of therapy, meet at least 1 criterion for treatment according to International Workshop on WM (IWWM) consensus panel criteria, and have good performance status. Patients eligible for reimbursement of Brukinsa should not have disease transformation, which is WM that has transformed into another type of cancer, or received prior treatment with a drug of the same class (i.e., a Bruton tyrosine kinase [BTK] inhibitor) unless such therapy was stopped because the drug was not tolerated and the disease had not progressed. Brukinsa should only be reimbursed if prescribed by a clinician with expertise and experience in the treatment of WM and monitoring of therapy and if it does not cost more than other treatments for WM.

Romosozumab (Evenity)

CADTH recommends that Evenity should be reimbursed by public drug plans for the treatment of osteoporosis in postmenopausal women if certain conditions are met. Evenity should only be covered to treat postmenopausal women with a history of osteoporosis-related fracture and who are likely to have such a fracture in the future and who have never received previous medications for osteoporosis. Evenity should only be reimbursed if the cost is reduced and if it is not prescribed concurrently with other osteoporosis medications, except for calcium and/or vitamin D.

Trientine Hydrochloride (MAR-Trientine)

CADTH recommends that MAR-Trientine should be reimbursed by public drug plans for the treatment of patients with Wilson's disease if certain conditions are met. MAR-Trientine should only be covered to treat patients who have previously tried and demonstrated intolerance to d-penicillamine. MAR-Trientine should only be reimbursed if initiated by clinicians experienced in the management of Wilson’s disease and if the cost of MAR-Trientine is reduced.

Tucatinib (Tukysa)

CADTH recommends that Tukysa should be reimbursed by public drug plans for the treatment of patients with advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer that cannot be removed by surgery or is metastatic, including patients with brain metastases, if certain conditions are met. Tukysa should only be reimbursed if prescribed in combination with trastuzumab-capecitabine and the cost of Tukysa is reduced. Tukysa should only be covered to treat patients who have been previously treated for HER2-positive breast cancer with trastuzumab, pertuzumab, and trastuzumab emtansine (T-DM1).

Idecabtagene Vicleucel (Abecma)

CADTH recommends that Abecma should not be reimbursed by public drug plans for the treatment of multiple myeloma. Evidence from a clinical trial suggested that Abecma is associated with an improvement in response rate in patients with heavily treated multiple myeloma. No conclusions could be drawn for other important outcomes, including duration of response, overall survival, progression-free survival, and quality of life. Patients identified a need for treatments that can prolong remission and improve quality of life and symptoms, and that have fewer side effects. It is not clear whether Abecma meets these needs.

Biologics in Plaque Psoriasis

Health Canada has approved 11 biologics for the treatment of adults with moderate-to-severe plaque psoriasis (PsO). These biologics can be divided into 2 groups based on mechanisms of action and market authorization dates: Old-generation biologics (5): include anti–tumour necrosis factor (TNF) agents (etanercept, adalimumab, infliximab, and certolizumab pegol) and an anti-interleukin (IL)-12/IL-23 inhibitor (ustekinumab) which were approved in Canada before 2010. New-generation biologics (6): include anti-IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) and anti-IL-23 inhibitors (guselkumab, tildrakizumab, and risankizumab) which were approved in Canada in 2015 or later. Patent protection has expired for infliximab, certolizumab, and ustekinumab. There is no valid data protection status for all 5 older generation biologics. However, only 3 of the old-generation biologics have biosimilar versions (adalimumab, etanercept, and infliximab) that are available in the Canadian market. Biosimilar versions for adalimumab and etanercept were marketed for PsO approximately 3 years to 4 years after their initial Notice of Compliance was issued, respectively. This delay can be attributed to various factors, including litigation and global agreements between manufacturers. Despite the expiry of data and patent protection for both ustekinumab and certolizumab, no biosimilar versions are available in Canada. Data protection for both biologics expired more than 4 years ago, and the patents have expired in 2021. A lack of a biosimilar entrant in Canada could be attributed to various factors, including clinical trial development based on exclusivity timelines in the US, where data protection is 4 years longer for biologics versus Canada. CADTH has reviewed 3 of 5 of the old-generation biologics and all 6 of the new-generation biologics; all drugs received similar CADTH Canadian Drug Expert Committee (CDEC) recommendations. The clinical programs of most of the new-generation biologics included direct evidence demonstrating superiority or statistically significantly higher efficacy outcomes compared with the active comparator of the old-generation biologics. The clinical trials for new-generation biologics also incorporated more stringent primary outcome measures. The old-generation biologics predated the pan-Canadian Pharmaceutical Alliance (pCPA) process (except for certolizumab), which could imply disparate product listing agreements across public drug plans for these drugs. The only biologics not included on any public formularies are certolizumab, guselkumab, and tildrakizumab (although tildrakizumab has yet to begin pCPA negotiations). Listing status for biologics fell under restricted benefit, but differed in terms of active (e.g., review through special authorization forms) versus passive (e.g., Limited Use codes in Ontario) procedures across public drug plans. Moreover, 3 public drug plans employed 2-tiered formularies (i.e., Alberta, Manitoba, and Correctional Services Canada) which required a trial of new-generation biologics or old-generation biosimilars before reimbursement of old-generation originators. Utilization patterns of old- versus new-generation biologics within the Ontario Public Drug Programs demonstrated that a significant proportion of new patients were treated with old-generation biologics (54% in 2019 and 37% in 2020) despite the availability of multiple new-generation biologics. In conclusion, formulary management is warranted for biologics for PsO given the significant utilization of old-generation originators in the current context of delayed marketing of their biosimilar versions for PsO and their reimbursement predating the pCPA process. New-generation biologics underwent pCPA negotiations and direct evidence was submitted that demonstrated superiority versus old-generation biologic active comparators, which may ultimately prove to be a greater value for patients and payers.