Real-world Evidence Showed Fewer Healthcare Visits with Prophylactic Treatment in Rare Disease

Rare diseases pose a substantial burden to patients and the healthcare system, comparable to those of cancer and heart failure.^[i] Thankfully, advances in diagnosis and healthcare delivery can help alleviate the burden of disease, prevent unnecessary interventions, reduce health resource use, and guide selection of optimal treatments, all of which can help address strains on the healthcare system.^[ii]

The potential of targeted treatment to minimize disease burden is evident in patients with hereditary angioedema (HAE), a rare disease characterized by recurrent swelling attacks that affect approximately 1 in 50,000 people in the United States.^[iii] The attacks – which occur two to three times per month on average^[iv] – can cause pain, reduced functioning, and poor quality of life. They can even be fatal. Patients hospitalized with HAE remain in the hospital for more than five days each visit, on average.^[v]

Preventing HAE attacks is critical, and ORLADEYO® (berotralstat), the only FDA-approved oral, once-daily preventative (prophylactic) treatment option for HAE, has been available since 2020. ORLADEYO is a prescription medicine used to prevent HAE attacks in patients 12 years and older. ORLADEYO is not approved for the treatment of acute attacks, and additional doses of ORLADEYO are not recommended due to the potential for QT prolongation. See the full Important Safety Information below. In clinical trials, ORLADEYO has been shown to be safe and effective - in addition to reducing HAE attacks, improvements in quality of life were observed.^[vi],[vii]

Extensive studies have also demonstrated the clinical and economic benefits of ORLADEYO in the real-world setting. A real-world study using specialty pharmacy data in the US showed that patients who started ORLADEYO experienced substantial and sustained reductions in HAE attack rates over 18 months of treatment regardless of their baseline attack frequency.^{[iv],[viii],[ix], [x]} ORLADEYO’s impact on healthcare resource utilization was highlighted in a recent retrospective study. Over a two-year period, the study reported a 34 percent decrease in all-cause hospitalizations and a 14 percent decrease in all-cause outpatient or emergency department visits in patients after initiating ORLADEYO. Treatment with ORLADEYO was also associated with significant reductions in HAE attack-related medical visits, including a 60 percent decrease in hospitalizations and a 50 percent decrease in outpatient or emergency department visits. Furthermore, the use of on-demand medications to treat HAE attacks in the clinic decreased by 32 percent after ORLADEYO initiation.^[xi]

"We are fortunate to have long-term prophylactic treatment (LTP) options for HAE which carry the potential to normalize patients’ lives. Unfortunately, patients may face barriers with approval for coverage of these transformational therapies. The totality of costs to the healthcare system, including those accrued from sub-optimally controlled disease, are essential considerations, however, when making coverage decisions,” explains Sandra Christiansen, MD, professor of medicine and director of translational research at the US HAEA Angioedema Center at the University of California, San Diego. "Evidence from this study supports adopting this holistic view of HAE care. Oral LTP treatment use was shown to achieve a significant reduction in the utilization of healthcare resources. This outcome is welcome news for all - improved HAE control translates into a reduction in disease burden for patients and cost for payors."

"We are committed to providing the broadest benefit possible to patients with HAE," noted Sandra Nestler-Parr, senior vice president, value and patient access, BioCryst, the maker of ORLADEYO. "By generating real-world evidence, we are able to show that our effective oral LTP option can not only meet the needs of patients but benefits the healthcare system as well."

U.S. Indication and Important Safety Information

INDICATION
ORLADEYO^® (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

Limitations of use

The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation.

IMPORTANT SAFETY INFORMATION
An increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent.

The most common adverse reactions (≥10 percent and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.

A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) and in patients taking chronically administered P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors (e.g., cyclosporine).

Berotralstat is a substrate of P-gp and BCRP. P-gp inducers (e.g., rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO.

ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (e.g., digoxin) when coadministering with ORLADEYO.

The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established.

There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production.

To report SUSPECTED ADVERSE REACTIONS, contact BioCryst Pharmaceuticals, Inc. at 1-833-633-2279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information.