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APeX-2 and APeX-S trials of Orladeyo shows reductions in attack and quality of life benefits in hereditary angioedema.- BioCryst Pharma

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Published:2nd Jul 2022

BioCryst Pharmaceuticals announced new long-term efficacy and safety data from the APeX-2 and APeX-S clinical trials evaluating oral, once-daily Orladeyo (berotralstat) for the prophylactic treatment of hereditary angioedema (HAE) showing sustained reductions in attack rates and improvement in quality of life (QoL) among patients living with HAE, and improved management of symptoms after switching to Orladeyo from an injectable long-term prophylactic treatment (LTP).


APeX-S was an open-label, international study that evaluated safety and tolerability of Orladeyo 110 mg and 150 mg in HAE patients. This analysis assessed the attack-free status in all patients who switched from lanadelumab to Orladeyo 150 mg at U.S. sites (n=21). Consistently low attack rates were observed in these patients, with median attack rates following the switch to Orladeyo monotherapy of 0.0 throughout 12 months of treatment with Orladeyo. The mean (SEM) monthly attack rate after Month 1 was 0.1 (0.08), which was sustained through Month 6 (0.5 [0.24]) and Month 12 (0.2 [0.15]). Patients remained attack free an average of 98 percent of days during treatment with Orladeyo, with a mean (SEM) of 144 (23.7) days and a maximum duration of 411 days between attacks.

These data demonstrate that Orladeyo is effective at maintaining good control of HAE symptoms in patients who switch from subcutaneous LTP treatments such as lanadelumab.

APeX-2 included 121 HAE patients who were randomized 1:1:1 to Orladeyo 110 mg or 150 mg, or placebo, once daily for 24 weeks (part 1 of the study). This analysis stratified patients who remained on study through at least Week 96 into three groups according to their duration of treatment with Orladeyo 150 mg: patients who received Orladeyo 150 mg for 96 weeks (n=21), patients who received Orladeyo 110 mg or placebo for part 1, Orladeyo 110 mg for part 2 and 150 mg for part 3 (n=37), and patients who received placebo for part 1 and Orladeyo 150 mg for parts 2 and 3 (n=12). Quality of life (QoL) was assessed using the Angioedema Quality of Life Questionnaire (AE-QoL), a validated tool to measure QoL impairment in patients with recurrent angioedema. The minimal clinically important difference (MCID) was defined as a change of six points in total score.

A sustained reduction in HAE attack rates was observed across all three groups, as patients treated with Orladeyo 150 mg had median attack rates of 0.0 in 21 of 24 months of treatment following initiation of the 150 mg dose. Patients also reported an overall improvement in their QoL, with the largest improvement observed in the functioning domain. For total AE-QoL score, a mean improvement (SEM) of 16.4 (2.79) points from baseline to Week 96 was observed, suggesting Orladeyo had a positive impact on day-to-day activities. These data further demonstrate that Orladeyo is generally well tolerated and an effective prophylactic therapy that reduces attack rates and improves QoL in patients with HAE.

Overall, 96 weeks of treatment with Orladeyo 150 mg resulted in 2.4 fewer doses per month of injectable on-demand therapy at Week 96 as compared to baseline. The median number of attacks per month requiring treatment with injectable on-demand medication was 0.0 attacks at all post-baseline timepoints throughout the 96 weeks of treatment, and a similar trend was observed with mean attack rates. These data suggest that use of Orladeyo leads to an increase in needle-free days for patients with HAE due to the reduced need for use of injectable on-demand medication.

The data are being presented in Flash Talks at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2022, which is being held live in Prague, Czech Republic, and virtually, from July 1-3, 2022.

Condition: Hereditary Angio-Oedema
Type: drug

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