1. Summary of Manufacturer’s Submission

2. Manufacturer’s Results

The manufacturer submitted a cost comparison of drug prices over a one-year time horizon from the perspective of a public drug plan comparing Tio R 5 with Tio H 18 under the assumption of similar clinical efficacy and harms based on the results of two 4-week head-to-head efficacy trials⁷ as well as the large, long-term TIOSPIR safety trial.^4–6 As secondary comparators, the manufacturer also compared Tio R 5 with glycopyrronium and with aclidinium, the other two LAMAs available in Canada. Drug costs were taken from the ODB Formulary with the exception of Tio R 5, the price of which was submitted confidentially by the manufacturer. An 8% markup was included and a dispensing fee of $8.83 was assumed every 30 days. The manufacturer concluded that Tio R 5 was ▬ to glycopyrronium and aclidinium bromide and would save ▬ per patient annually compared with Tio H 18 (Table 2).

A sensitivity analysis considering only listed drug prices (i.e., without markup or dispensing fees) found that the use of Tio R 5 ▬ per patient per year compared with Tio H 18.

3. CADTH Common Drug Review Results

While head-to-head trials exist comparing the clinical efficacy⁷ and safety^4–6 of Tio R 5 with Tio H 18, there are currently no trials available that compare Tio R 5 with glycopyrronium or aclidinium bromide. Mixed-treatment comparisons exist^8,9 that compare Tio R 5 with other LAMAs as well as LABAs, ICS/LABAs, and placebo in terms of COPD exacerbations or mortality; however, limitations of these studies and the inconsistency of their results with those of the TIOSPIR trial suggest that the results should be interpreted with caution (see CDR Clinical Report, Appendix 6). The clinical similarity of Tio R 5 to glycopyrronium and aclidinium bromide is less certain; thus, ▬ ▬ ▬ Tio R 5 to these comparators is also less certain.

While the other LAMA products are the most direct comparators to Tio R 5, current COPD guidelines^10,11 also recommend LABAs or ICS/LABAs as appropriate alternatives to LAMA therapy for some portions of the patient population within Tio R 5’s approved indication. For example, the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend a LAMA or a LABA for patients with significant symptoms at low risk of exacerbations (Group B), a LAMA or an ICS/LABA for patients with few symptoms at high risk of exacerbation (Group C), and a LAMA and/or an ICS/LABA for patients with many symptoms and a high risk of exacerbation (Group D).

CDR compared the annual cost per patient of Tio R 5 with that of the available LABA and ICS/LABA products. Alberta Health’s list prices (without markup or fees) were used for the comparators rather than ODB Formulary prices, as Alberta Health reimburses more LABA-containing products for patients with COPD; LAMA list pricing was identical between ODB and Alberta Health in April 2015. At the submitted price, Tio R 5 is less expensive than all ICS/LABA fixed-dose combinations, but is more expensive than some LABA-only products (Table 3).

According to current guidelines for the management of COPD, it is appropriate for some patients to be treated with a LAMA plus a LABA, or a LABA plus an ICS (e.g., alternate therapy choices for patients defined as Group B, C, or D by the 2015 GOLD guidelines¹¹).

As shown in Table 4, the cost (without markup or fees) of Tio R 5 in combination with the available LABA products ranges from ▬ to ▬ per patient per year, while the annual per-patient cost of the indacaterol/glycopyrronium and umeclidinium/vilanterol fixed-dose combination inhalers is $978 and $1,069, respectively. Thus, for patients requiring combination therapy with a LAMA plus a LABA, the available LABA/LAMA fixed-dose combinations ▬ ▬ ▬ all possible combinations that include Tio R 5. While not included in Table 4, the use of a LABA/LAMA fixed-dose combination rather than Tio R 5 plus an individual LABA would also save a dispensing fee every 30 to 90 days, depending on refill interval.

4. Key Limitations