Bookshelf

Decision tree and Markov model

• Indirect treatment comparison using patient-level data from single-arm ANNEXA-4 and UK Oral Anticoagulant Agent-Associated Bleeding Events Reporting System (ORANGE) studies to evaluate efficacy.
• Additional sources include 2 retrospective studies based on real-world evidence and ANNEXA-4 and RETRACE-II studies for long-term mortality.

• Long-term survival for patients with ICH using andexanet alfa is overestimated. Results from the ANNEXA-4 vs. RETRACE-II trial were used to inform the distribution of mRS scores in the ICH survivor clinical population. Feedback obtained from clinical experts consulted by CADTH highlighted that they did not expect a difference in survival or mRS distribution for patients prescribed andexanet alfa compared with those prescribed PCC. The CADTH clinical review notes that the mean difference for mRS at discharge from the ANNEXA-4 vs. RETRACE-II trial was not statistically significant and there is insufficient evidence to justify different mRS distributions between the 2 treatment groups.
• Comparative clinical effectiveness of andexanet alfa is uncertain. In the absence of direct comparative evidence, the sponsor assumed a 30-day mortality relative risk of 0.43 (95% CI, 0.29 to 0.63) for andexanet alfa. The CADTH clinical review appraisal of the sponsor-submitted ITC noted that several limitations preclude definitive conclusions regarding the comparative efficacy of andexanet alfa and PCC.
• Comparator pricing is based on publicly available prices. The sponsor’s analysis estimated of the cost of PCC using published list prices for Beriplex and Octaplex in the PMPRB basket of 11 comparator countries. Unit prices for Beriplex and Octaplex were only available in 2 and 3 of the 11 countries, respectively. The price of PCC (Beriplex and Octaplex) does not reflect any confidential pricing that may have been negotiated by the CBS; therefore, the estimated drug acquisition costs for PCC are uncertain.

• CADTH revised the sponsor’s model by setting ICH utilities to be equal in both the andexanet alfa and PCC treatment groups. Additionally, mRS distributions were set to be equal between treatment groups.
• CADTH’s base case: ICER = $61,865 per QALY gained (incremental cost = $36,604; incremental QALYs = 0.592). A price reduction of at least 27% would be required to achieve cost-effectiveness at a willingness-to-pay threshold of $50,000 per QALY gained.