BioCryst Pharmaceuticals, Inc. announces 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 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).

The data are being presented in Flash Talks at the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress 2022.

“From each additional analysis of our long-term data from APeX-2 and APeX-S, we continue to see more examples of the positive long-term impact our oral, once-daily prophylactic therapy is having on patients with HAE. Since first reporting our 96-week data at last year’s EAACI congress, we have seen increased evidence of sustained improvement in quality of life, reductions in attack rates and decreased need for use of injectable on-demand therapy. These data, coupled with the real-world evidence and feedback we are gathering from patients and physicians, confirm our confidence in ORLADEYO as a meaningful treatment option for patients with HAE,” says Dr. William Sheridan, Chief Medical Officer of BioCryst.

“The analysis of the attack-free status of patients with HAE who switched from injectable LTP therapy to ORLADEYO in APeX-S builds on previous data that have shown consistently low attack rates in ORLADEYO patients. These findings suggest there are excellent reasons for patients to speak with their physicians to determine if switching to an oral prophylactic therapy could be an option to help them reduce their burden of disease while maintaining strong efficacy. Additionally, the analysis from APeX-2 of long-term efficacy and quality of life data following initiation of the 150 mg dose demonstrates ORLADEYO is having a positive impact on patients as they focus on their daily activities,” says Teresa Caballero, M.D., Ph.D., Allergy Department, Hospital Universitario La Paz, Madrid, Spain.

BioCryst EAACI 2022 Presentation Highlights

APeX-S was an open-label, international study that evaluated safety and tolerability of ORLADEYO 110 mg and 150 mg in HAE patients. In APeX-S, the switch from LTP (lanadelumab) to ORLADEYO was generally well-tolerated among patients, with no patients in this analysis discontinuing ORLADEYO due to an adverse event.

Attack-free Status in Patients who Switched from Subcutaneous Lanadelumab to Oral Berotralstat:

  • 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). At Week 24, patients on ORLADEYO continued on the same dose and placebo patients were re-randomized to ORLADEYO 110 mg or 150 mg for another 24 weeks (part 2 of the study). At Week 48 and thereafter, all patients continued on ORLADEYO 150 mg (open-label phase). In APeX-2, ORLADEYO was safe and generally well tolerated, with no drug-related serious adverse events reported.

Improvement in Quality of Life and HAE Attack Rates Observed in Patients Treated with Long-term Berotralstat in the APeX-2 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.

96 Weeks of Treatment with Berotralstat Consistently Decreases the Use of Injectable On-Demand Medication to Treat HAE Attacks:

  • This analysis assessed injectable on-demand medication use in patients who were originally randomized to ORLADEYO 150 mg and completed 96 weeks of therapy (n=21).
  • 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. ORLADEYO was safe and well tolerated in clinical trials. The most frequently reported adverse reactions in patients receiving ORLADEYO compared with placebo were back pain and gastrointestinal reactions. The gastrointestinal reactions generally occurred early after initiation of treatment with ORLADEYO, became less frequent with time and typically self-resolved.

(Source: BioCryst)