A Long Term Safety Study of BCX7353 in Hereditary Angioedema

The number and percentage of subjects with treatment-emergent adverse events.

Time frame: Up to 96 weeks (US) / 216 weeks (Rest of World (ROW)).

Population: The safety population included all subjects who received at least 1 dose of study drug. This population was used in the assessment and reporting of safety data.

Number of 'adjusted' attacks were assessed. Adjusted attacks included at least 1 symptom of swelling, had a response of 'no' to the diary question, 'In retrospect, could there be an alternative explanation for your symptoms other than an HAE attack (i.e., allergic reaction, viral cold etc.)?', and were considered unique (attack began \> 24 hours from the end of the prior attack). Any attack that began within 24 hours from the end of a prior attack was combined with the prior attack.

Time frame: Up to 96 weeks (US) / 216 weeks (ROW)

Population: The safety population included all subjects who received at least 1 dose of study drug. This population was used in the assessment and reporting of efficacy data.

Quality of Life (QoL) specific to hereditary angioedema (HAE) was assessed at baseline and at each study visit until the end of the study. The questionnaire (i.e. AE-QoL) consisted of 17 questions spanning 4 domains (functioning, fatigue/mood, fear/shame, and nutrition). Each AE-QoL question had 5 answer options (scored 1-5), with lower and higher scores indicting less and more adverse impact, respectively. Per-subject scores for each domain were computed using the appropriate scoring algorithm applied to the question response scores for each domain. Per-subject total scores (including all 4 domains) were similarly computed using the question response scores for all 17 questions. The outputs from the scoring algorithm were normalized on a scale ranging from 0 (less adverse impact) to 100 (most adverse impact). The Mean change from baseline (CFB) in AE-QoL total score over time is presented below.

Time frame: Up to 96 weeks (US) / 216 weeks (ROW)

Population: The safety population was used in the assessment \& reporting of efficacy data, \& included subjects receiving at least 1 dose of study drug. The reduced number of subjects analysed at each study period reflects that the maximum duration for US subjects was 96 weeks, variation in the number of subjects completing the AE-QoL questionnaire \& subject withdrawal prior to study completion, primarily as a result of Berotralstat being provided via an early access program or commercially.

The Treatment Satisfaction Questionnaire for Medication (TSQM) was completed by subjects at baseline and at each study visit until the end of the study. TSQM scores consisted of 14 items of which 13 items were made up of 3 specific scales (Effectiveness, Side Effects, and Convenience) and 1 global satisfaction scale (Global Satisfaction). At baseline, TSQM questionnaires were completed based on subject's satisfaction with usual medications. At all other time points for collection of TSQM, subjects were asked about their level of satisfaction or dissatisfaction with the study drug. Scale scores were calculated for each scale and were transformed into scores ranging from 0 to 100, with higher scores indicating higher satisfaction. TSQM score and corresponding change from baseline values were calculated at each visit. Note: Subjects in Hong Kong did not complete the TSQM.

Time frame: Up to 96 weeks (US) / 216 weeks (ROW)

Population: The safety population was used in the assessment \& reporting of efficacy data, \& included subjects receiving at least 1 dose of study drug. The reduced number of subjects analysed at each study period reflects that the maximum duration for US subjects was 96 weeks, variation in the number of subjects completing the TSQM questionnaire \& subject withdrawal prior to study completion, primarily as a result of Berotralstat being provided via an early access program or commercially.

To evaluate if the rate of attacks remains consistent (durable) over time, the monthly attack rate was assessed at 0 to 24 weeks, 24 to 48 weeks, 48 to 96 weeks and 96 weeks until the end of the study. Monthly attack rate was defined as the total number of adjusted HAE attacks experienced during the treatment period adjusted for the length of a month (defined as 28 days) and the number of days the subject was on treatment during that month.

Time frame: Up to 96 weeks (US) / 216 weeks (ROW)

Population: The safety population included all subjects who received at least 1 dose of study drug. This population was used in the assessment and reporting of efficacy data. The reduced number of subjects analysed at each study period reflects the fact that the maximum duration for US subjects was 96 weeks, as well as subject withdrawal prior to study completion, primarily as a result of Berotralstat being provided by alternative means (i.e., early access program or commercially available).