Orladeyo helps HAE patients spend more days attack-free: Trial analysis
Benefits are long-term, regardless of age, sex, or prior preventive treatments
Preventive treatment with Orladeyo (berotralstat) for up to two years led to prolonged periods of no swelling attacks in people with hereditary angioedema (HAE), irrespective of age, gender, or prior preventive treatments, according to a post-hoc analysis of the Phase 2/3 APeX-S trial.
“These data demonstrate how our oral, once-daily prophylactic [preventive] treatment can consistently help patients spend more of their days without disruption from HAE attacks, regardless of their age, gender and experience with prior prophylactic treatment, including among pediatric patients aged 12-17,” Ryan Arnold, chief medical officer of BioCryst Pharmaceuticals, which is developing Orladeyo, said in a company press release.
“These additional analyses of long-term data reflect our continued commitment to define the potential benefits and bring Orladeyo to as many HAE patients around the world as possible,” Arnold said.
The findings from the post-hoc analysis will be presented by Avner Reshef, MD, director of the Allergy, Immunology and Angioedema Center at the Barzilai University Medical Center in Israel, at the 13th C1-inhibitor Deficiency & Angioedema Workshop, held May 4-7, in Budapest, Hungary. His presentation, scheduled for May 6, is titled “Attack-free status across subgroups of patients with hereditary angioedema (HAE) after 96 weeks of berotralstat treatment: results from the APeX-S trial.”
APeX-S trial tested safety and effectiveness of 110 mg or 150 mg of Orladeyo
People with HAE experience swelling attacks due to an overproduction of a signaling molecule called bradykinin, which promotes blood vessel widening and increases their permeability. Attacks can occur in different parts of the body, such as in the face, throat, arms and legs, or around the gut.
The disease is mainly caused by mutations in the SERPING1 gene, which carries instructions for making the C1-inhibitor (C1-INH) protein. C1-INH blocks the activity of two other proteins — plasma kallikrein and coagulation factor 12, which promote the production of bradykinin.
Orladeyo is an approved oral medicine to prevent swelling attacks in HAE patients 12 and older. It works by blocking the activity of plasma kallikrein and preventing bradykinin levels from rising too high and triggering an attack.
The open-label APeX-S trial (NCT03472040) evaluated the safety and effectiveness of either 110 mg or 150 mg of Orladeyo, given once daily for up to 96 weeks (nearly two years) in the U.S. and 240 weeks (nearly five years) elsewhere.
As previously reported, treatment-emergent side effects were mild and lasted a short time, indicating that Orladeyo was generally well-tolerated.
We continue to generate evidence that further strengthens confidence in Orladeyo as a safe, effective and more convenient therapeutic option for people living with HAE.
Patients on 150 mg of Orladeyo experienced significant reduction in attack rates
Overall, patients treated with 150 mg of Orladeyo, its approved dose, experienced a significant reduction in attack rates after 96 weeks of treatment. Attack rates dropped from a mean of 1.08 in the first 24 weeks of treatment to 0.69 in weeks 25-48 and to 0.59 in weeks 49-96.
In these new post-hoc analyses, researchers focused on evaluating the effects of Orladeyo on 287 patients who were consistently treated with 150 mg of the medication for 96 weeks, according to their age, gender, and prior use of preventive HAE treatments. Of note, post-hoc analyses are those conducted after a trial has been completed.
Patients were divided into three groups based on their age: 23 were in a group for ages 12-17 years, 253 were in a group for ages 18-64 years, and 11 were in the 65-and-older group. Of the patients, 180 were female and 107 were male. Previous preventive HAE treatments included androgens, which were used by 142 patients, or C1-inhibitor products, which were used by 105 patients.
Orladeyo’s benefits seen in all subgroups of patients
According to the new analyses, the proportion of patients who remained attack-free over the course of 96 weeks of Orladeyo treatment was high, regardless of their age, gender, and prior preventive HAE treatment.
On average, younger patients (ages 12-17 years) remained attack-free on 97% of the days, while those 65 years and older remained attack-free on 98% of the days. The number of days between attacks reached a maximum of 461 days (about a year and three months) for younger patients and 1,182 days (nearly three years and three months) for older patients. Patients ages 18-64 were free of attacks on 94% of the days, with a maximum number of 1,101 days (about three years) between attacks.
Both female and male patients remained attack-free on 94% of the days on average. The number of days between attacks reached a maximum of 1,182 days (nearly three years and three months) for women and 1,101 days (about three years) for men.
Patients previously treated with androgens remained attack-free on 93% of the days on average, with a maximum number of 1,026 days (nearly two years and 10 months) between attacks. A maximum number of 584 days (1.6 years) between attacks were seen in those previously treated with C1-inhibitors, who remained attack-free on 91% of the days on average.
“We continue to generate evidence that further strengthens confidence in Orladeyo as a safe, effective and more convenient therapeutic option for people living with HAE,” Arnold said.
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