2 Family Members Make Swift Switch to Oral Orladeyo Successfully

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Switching from under-the-skin injections to oral pills of Orladeyo (berotralstat), a preventive treatment, can be done without the need to taper prior therapy or go through complex regimens, according to a case study of a patient and her mother, both of whom have hereditary angioedema (HAE).

The report, “Patient and caregiver perspectives on transitioning to oral prophylaxis in the emerging hereditary angioedema treatment landscape,” was published in the journal Clinical Case Reports.

HAE is a rare genetic disorder characterized by the lack of a functional blood protein called C1-inhibitor, leading to sudden and recurrent swelling episodes. The standard course of long-term treatment consists of under-the-skin and into-the-vein injections as preventive (prophylactic) therapies to reduce swelling episodes.

Routine injectable treatments, however, are known to place a large burden on HAE patients and their caregivers, and an oral preventive therapy would be easier to take, thereby improving patient quality of life and independence.

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BioCryst Pharmaceuticals’ Orladeyo is a widely approved oral treatment to prevent swelling attacks in people with HAE. It works by preventing bradykinin levels from rising too high. Bradykinin is the inflammatory molecule that drives swelling in HAE.

Orladeyo’s approval was based on results from clinical trials, including the Phase 2/3 APeX-S trial (NCT03472040).

No guidelines are available for transitioning to an oral HAE therapy, but there are concerns over the possibility of worsening symptoms and other complications that may arise from the switch.

In the case report, researchers described the experiences of a mother and daughter who have HAE and participated in the APeX-S trial and who also safely transitioned from a preventive under-the-skin formulation to oral Orladeyo.

The patients answered two questionnaires, one for the patient and the other for the caregiver perspective, about the transition.

The daughter, 13, had type 1 HAE diagnosed at age 10. Before enrolling in APeX-S, she was receiving preventive therapy, given under the skin (subcutaneously), for nearly two years (23 months).

The treatment worked well for her. While she “barely had any attacks,” she enrolled in the APeX-S trial because she “would rather take a pill than take an injection twice a week.”

After starting oral Orladeyo (150 mg once-daily pill), she experienced mild gastrointestinal discomfort, but these resolved when the pill was taken before dinner.

She continued her subcutaneous injections, including Orladeyo (dual therapy) for around four months, without additional adverse events or HAE attacks experienced.

Then, because she “did not like taking injections, and a pill sounded easier and saved more time,” the girl started taking oral Orladeyo alone without tapering the dose or reducing the frequency of injections.

She received Orladeyo for three months during which she experienced a single HAE attack. This resolved with one dose of on-demand into-the-vein treatment with Ruconest.

Since transitioning to oral Orladeyo, her quality of life improved and she was able to participate in extracurricular activities, which she couldn’t have done before.

The second case was the girl’s 41-year-old mother, her main caregiver, who was diagnosed with type 1 HAE at age 14. The woman has a second child with HAE, but the child “was too young to enroll in the APeX-S study at the time,” the researchers noted.

As a patient, the woman had received weekly into-the-vein preventive therapy for six months, which were challenging.

“My husband had to do it; I couldn’t do it on myself, which was difficult,” she said.

She then switched to subcutaneous injections, administered every four days for nine months before enrolling in the APeX-S trial. During this period, she experienced two HAE attacks.

She enrolled in APeX-S because, she said, “I do not like taking injections. The process is cumbersome and requires more planning and time than a pill. With three of us needing medication and supplies, it takes up traveling space and time.”

After joining the trial, she began Orladeyo (150 mg once-daily oral pill) while maintaining her subcutaneous injections. She took Orladeyo with dinner and experienced an occasional “upset stomach,” depending on the type of meal. Poorer meal choices for dinner tended to result in worse discomfort.

She continued the dual therapy for around 3.5 months without any attacks.

She switched to oral Orladeyo alone to “see if a pill would work on its own. I hadn’t had attacks for some time, so I didn’t mind taking a minor risk to see if a tablet would be enough [to control my symptoms],” she said.

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The switch was immediate without tapering the dose or frequency of the injections. She has been treated with Orladeyo for about four months and experienced one HAE attack. This was resolved with on-demand treatment.

The impact on her life is positive, with the oral therapy being “much more convenient, much easier, and requires less preparation and planning,” she said. “Most people, including myself, would much rather take a pill to control this, daily, than have to come up with twice-a-week injections.”

From a caregiver’s perspective, she said that oral Orladeyo requires much less time and has reduced her anxiety and stress.

“It’s less stress on everyone,” she added. “It’s a lot easier to make the decision to let her travel independently. I don’t have to worry about her taking that medication on a plane or injecting it in a hotel room with a bunch of kids.”

As a mother and caregiver, she noticed improvements in her daughter’s quality of life since the girl switched to oral Orladeyo. “She loves it, she enjoys it; she has never liked needles. She would much rather take a pill because it doesn’t interfere with her other activities.”

Overall, this case report describes the successful transition of two HAE patients from injectable to oral preventive treatment without tapering prior therapy or employing a complex transition protocol.

According to the researchers, “important considerations that contributed to the successful transition of both patients in this report include (1) shared decision-making that included the goals and preferences of the patients before, during, and after transition, (2) scheduling the therapy transition during a time when the patient felt comfortable and was not experiencing high levels of stress, and (3) observing the patient closely during the transition period for any changes in HAE symptoms or adverse events related to the new prophylactic medication.”

They emphasized that more studies and real-world evidence are needed “to develop a standard protocol for transitioning patients from one HAE prophylactic therapy to another in clinical practice.”