Decision tree plus a Markov model

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

• The long-term survival for ICH survivors using andexanet alfa is overestimated. Results from the ANNEXA-4 trial vs. the RETRACE-II study were used to inform the distribution of mRS scores in the ICH survivor clinical population. Feedback obtained from the clinical experts consulted by CADTH highlighted that they did not expect a difference in survival or distribution of mRS scores for patients prescribed andexanet alfa compared with PCC. The CADTH Clinical Review notes that the mean difference in mRS score at discharge from the ANNEXA-4 trial vs. the RETRACE-II study was not statistically significant and there is insufficient evidence to justify different mRS distributions between the 2 treatment groups.
• The 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 based on the ITC of the ANNEXA-4 and ORANGE trials. The CADTH Clinical Review appraisal of the sponsor-submitted ITC notes 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 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 available in only 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 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.