Canadian Journal of Health Technologies

Avapritinib (Ayvakyt)

CDA-AMC — Tue, 19 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Ayvakyt be reimbursed by public drug plans for the treatment of adult patients with advanced systemic mastocytosis (AdvSM), including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL), only if certain conditions are met.
Ayvakyt should only be covered to treat adult patients with AdvSM who have a diagnosis of ASM, SM-AHN, or MCL based on WHO criteria and have an Eastern Cooperative Oncology Group (ECOG) performance status score (which estimates patients’ ability to perform activities of daily living) of 0 (no symptoms, fully active) to 3 (symptomatic, confined to bed or chair 50% or more of waking hours). Patients with AdvSM who have low platelet counts are not eligible for Ayvakyt.
Ayvakyt should only be reimbursed if prescribed by medical teams with access to expertise in the diagnosis, treatment, and response evaluation of patients with AdvSM. It should only be reimbursed if the cost of Ayvakyt is reduced and the economic feasibility of Ayvakyt is addressed.

Ciltacabtagene Autoleucel (Carvykti)

CDA-AMC — Wed, 20 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Carvykti should be reimbursed by public drug plans for the treatment of adult patients with multiple myeloma (MM), who have received 1 to 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, and whose disease is refractory to lenalidomide if certain conditions are met.
Carvykti should only be covered to treat patients aged 18 years or older with documented diagnosis of MM, who have received 1 to 3 prior lines of therapy, and have a good performance status, as determined by a specialist. Carvykti should not be reimbursed for the treatment of patients whose MM is affecting their central nervous system. It should also not be reimbursed for patients who have previously received any treatment that targets B-cell maturation antigen (BCMA).
Carvykti should only be reimbursed if it is prescribed and administered by clinicians with expertise in the treatment of MM at specialized centres with adequate infrastructure, resources, and expertise to facilitate treatment with chimeric antigen receptor (CAR) T-cell therapy, and the cost of Carvykti is reduced.

Alectinib (Alecensaro)

CDA-AMC — Mon, 18 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Alecensaro should be reimbursed by public drug plans for adjuvant treatment following tumour resection for patients with stage IB (tumours ≥ 4 cm) to IIIA (according to American Joint Committee on Cancer [AJCC] Cancer Staging Manual, seventh edition) ALK-positive non–small cell lung cancer (NSCLC) if certain conditions are met.
Alecensaro should only be covered to treat adult patients (≥ 18 years) who have stage IB (tumour ≥ 4 cm) to stage IIIA (per the AJCC seventh edition) ALK-positive NSCLC, have had complete tumour resection, and are in relatively good health.
Alecensaro should only be reimbursed if it is prescribed by clinicians with expertise in managing NSCLC and the cost of Alecensaro is reduced. Alecensaro should be discontinued if a patient’s cancer grows or spreads, if treatment is unacceptably toxic to the patient, or the patient has completed 2 years of therapy with Alecensaro.

Lebrikizumab (Ebglyss)

CDA-AMC — Fri, 15 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Ebglyss should not be reimbursed by public drug plans for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents aged 12 years and older with a body weight of at least 40 kg, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.
Evidence from 3 clinical trials demonstrated that, in the short-term, Ebglyss treatment improved the severity of AD and reduced itch symptoms compared with placebo in adults and adolescents with moderate to severe AD. However, based on the evidence reviewed in the initial meeting and the reconsideration meeting, the Canadian Drug Expert Committee (CDEC) could not determine whether lebrikizumab would address the unmet needs of patients because of the uncertainty around the benefit of lebrikizumab versus appropriate comparators and in patients who received prior dupilumab or Janus kinase (JAK) inhibitor treatment.
No evidence was submitted that directly compared Ebglyss to currently available treatments for AD. The indirect evidence submitted had limitations that impacted the certainty of the evidence, and it was unclear if the estimates were valid.
The safety of Ebglyss relative to other treatments for AD is unknown because no comparative evidence was submitted. In addition, longer-term safety and efficacy was uncertain because of limitations of the study designs and analysis with the available evidence.

Sotatercept (Winrevair)

CDA-AMC — Wed, 06 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that sotatercept (Winrevair) should be reimbursed by public drug plans for the treatment of patients with WHO Group 1 pulmonary arterial hypertension (PAH) if certain conditions are met.
Winrevair should only be covered as add-on therapy in patients with confirmed WHO Group 1 PAH based on guidelines-approved diagnostic procedure including right-heart catheterization (RHC).
Winrevair should only be reimbursed as an add-on therapy in patients who are not at low risk, currently treated with optimal background therapy for at least 3 months, and if the cost of Winrevair is reduced.

Eplontersen (Wainua)

CDA-AMC — Wed, 06 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Wainua be reimbursed by public drug plans for the treatment of polyneuropathy (PN) associated with stage I or stage II hereditary transthyretin amyloidosis (hATTR) in adults, if certain conditions are met.
Wainua should only be covered to treat adults with stage I or stage II genetically confirmed hATTR with PN (hATTR-PN) who are symptomatic with early-stage neuropathy, do not have severe heart failure symptoms, and have not had a liver transplant. A patient’s response to treatment with Wainua should be assessed at least every 6 months to determine whether they would benefit from continued treatment. Treatment with Wainua should not be continued in patients who are permanently bedridden and dependent on assistance for basic activities of daily living or who are receiving end-of-life care.
Wainua should only be reimbursed if the patient is under the care of a specialist with experience in the diagnosis and management of hATTR-PN, and should not be reimbursed if it is used in combination with interfering ribonucleic acid (RNA) drugs or transthyretin stabilizers. The cost of Wainua should be reduced so that it does not cost more than other drugs for hATTR.

Clindamycin Plus Benzoyl Peroxide and Adapalene (Cabtreo)

CDA-AMC — Tue, 05 Nov 2024 00:00:00 -0800

It is recommended that Cabtreo be reimbursed by public drug plans for the topical treatment of acne vulgaris in patients 12 years of age and older if certain conditions are met.
Cabtreo should only be covered to treat patients 12 years of age and older with acne vulgaris.
Cabtreo should only be reimbursed if the price of Cabtreo is negotiated so that it does not exceed the drug program cost of treatment with topical therapy for acne vulgaris reimbursed by participating plans.

Danicopan (Voydeya)

CDA-AMC — Tue, 05 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Voydeya be reimbursed by public drug plans as an add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have residual hemolytic anemia due to extravascular hemolysis (EVH) if certain conditions are met.
Voydeya should only be covered to treat adult patients with a diagnosis of PNH, who have met the public drug plan reimbursement criteria for initiating complement 5 inhibitor (C5i) treatments (ravulizumab or eculizumab) before receiving C5i treatment, and who have been on a stable dose of C5i treatment for 6 months or more, in addition, patients should also have persistent anemia caused by EVH, and an absolute reticulocyte count of 120 × 10⁹/L or greater.
Voydeya should only be reimbursed if prescribed by a hematologist with experience managing PNH. The cost of Voydeya should be negotiated so that Voydeya plus a C5i as a regimen does not exceed the drug program cost of treatment with pegcetacoplan for the treatment of adult patients with PNH who have residual hemolytic anemia due to EVH.

Elexacaftor-Tezacaftor-Ivacaftor and Ivacaftor (Trikafta)

CDA-AMC — Mon, 04 Nov 2024 00:00:00 -0800

Canada’s Drug Agency (CDA-AMC) recommends that Trikafta be reimbursed by public drug plans for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least 1 of the 152 non-F508del mutations in the CFTR gene that are identified in Figure 1 of this document, if certain conditions are met.
Patients aged 2 to 5 years who start treatment with Trikafta should be evaluated for response after 1 year, and those aged 6 years or older should be evaluated after 6 months. The physician must provide evidence that the patient is benefiting from the treatment. The cost of Trikafta must also be reduced.

Pembrolizumab (Keytruda)

CDA-AMC — Fri, 08 Nov 2024 00:00:00 -0800

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform nonbinding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses pembrolizumab (Keytruda), 100 mg/4 mL vial, solution for infusion.
Indication: Pembrolizumab, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, whose tumours express PD-L1 (combined positive score [CPS] ≥ 1), as determined by a validated test.

Elranatamab (Elrexfio)

CDA-AMC — Thu, 07 Nov 2024 00:00:00 -0800

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses elranatamab (Elrexfio), 40 mg/mL, solution for subcutaneous injection supplied as 76 mg/1.9 mL (40 mg/mL) in a single-dose vial and 44 mg/1.1 mL (40 mg/mL) in a single-dose vial.
Indication: For the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

Aflibercept 8 mg/0.07 mL (Eylea HD)

CDA-AMC — Thu, 07 Nov 2024 00:00:00 -0800

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses aflibercept (Eylea HD) 8 mg (0.07 mL), solution for intravitreal injection.
Indication: For the treatment of neovascular (wet) age-related macular degeneration (nAMD).

Overview of Systematic Reviews of ICIs in NSCLC With EGFR, ALK, ROS1, and RET Actionable Driver Mutations

Thu, 14 Nov 2024 00:00:00 -0800

The effectiveness and safety of immune checkpoint inhibitor (ICI) monotherapy in patients with previously treated advanced or metastatic non–small cell lung cancer with EGFR, ALK, ROS1, or RET actionable driver mutations or chromosomal rearrangements is currently uncertain.

We assessed the efficacy and safety of ICIs in patients with this condition whose disease did not respond well to previous chemotherapy.

We reviewed 13 systematic reviews of randomized controlled trials (RCTs). The quality assessment of these reviews revealed critical methodological flaws.

All 13 systematic reviews focused on survival and progression-free survival (PFS) for patients with non–small cell lung cancer and EGFR gene mutations. The systematic reviews generally considered the same set of 4 clinical trials and did not report on other outcomes or patient groups, except for 1 review that looked at patients with different levels of anti-PD-L1 expression.

We found no evidence on the efficacy and safety of ICIs in patients with ALK, ROS1, or RET mutations.

Overall, the systematic reviews concluded that using ICIs alone, as a second-line therapy or beyond, does not significantly improve overall survival (OS) and PFS compared to chemotherapy in patients with non–small cell lung cancer with EGFR gene mutations.

No conclusions can be made regarding the benefits of ICIs in patients with EGFR mutations based on histology or high antiprogrammed death-ligand 1 antibody expression levels.

The safety of ICIs in patients with EGFR, ALK, ROS1, or RET actionable driver mutations could not be assessed because of the lack of evidence provided in the included systematic reviews.

Clinical Effectiveness and Safety of Midazolam Compared With Lorazepam for Control of Seizures in Adults

CDA-AMC — Tue, 05 Nov 2024 00:00:00 -0800

What Is the Issue?

The emergency treatment of prolonged seizures or status epilepticus is required to be rapid and efficient to prevent permanent brain damage or death.
Benzodiazepines, such as midazolam, lorazepam, diazepam, and clonazepam, are established as first-line treatment medications for acute treatments of seizures.
Various administration routes of delivery for these drugs have become available, but the comparative clinical effectiveness and safety among administration routes are still unclear.
Decision-makers are interested in whether the current use of intramuscular (IM) midazolam for treatment of seizures by paramedics in a prehospital environment can be switched to IV lorazepam as normally used by nurses and physicians in clinic settings.

What Did We Do?

We identified and summarized the literature on the evidence of the clinical effectiveness and safety of midazolam compared to lorazepam in adults to control seizures.
We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find?

We identified 1 systematic review (SR) that included 4 randomized controlled trials (RCTs), only 1 was relevant to this review. This double-blind RCT determined the efficacy of IM midazolam as noninferior to IV lorazepam for treatment of seizures by paramedics in a mixed population of adults (89%) and children (11%).
The authors of the SR conducted a subanalysis of a dataset of participant-level data and showed that IM midazolam was as effective and safe as IV lorazepam in adult patients for prehospital seizure cessation. The findings of the adult population were similar to those of the whole randomized population of both adults and children.

What Does This Mean?

With the shorter time required to administration of midazolam by the IM route compared to administration of lorazepam by the IV route, and the comparable efficacy and safety between the 2 active treatments, the use of IM midazolam may be a better option in the prehospital environment when IV access in patients with seizures is not readily established.
Switching of IM midazolam to IV lorazepam for treatment of seizures by paramedics may not be practical.