FDA Approves Berotralstat for Hereditary Angioedema prophylaxis
The US Food and Drug Administration has approved oral, once-daily ORLADEYO™ (berotralstat) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older on December 3, 2020.
"ORLADEYO offers people with HAE and their physicians the first orally administered non-steroidal option for preventing HAE attacks and represents an important and welcome step in making more treatment options available to physicians and patients," said Anthony J. Castaldo, president and chief executive officer of the US Hereditary Angioedema Association (HAEA).
ORLADEYO™ (berotralstat) has become the first drug approved by the U.S. Food and Drug Administration (FDA) indicated for HAE attack prophylaxis. Berotralstat is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) and at a dose of 150 mg, it is a moderate inhibitor of CYP2D6 and CYP3A4. In a pivotal Phase 3 APeX-2 trial, berotralstat significantly reduced HAE attacks at 24 weeks and sustained through 48 weeks. Among patients treated with 150 mg of berotralstat, the researchers observed a significant reduction in HAE attack from baseline (2.9)to 48 weeks(1.0). In a long-term open-label assessment of the same patient population, researchers observed a decrease to just 0.8 attacks monthly. In both the trials, berotralstat found to be safe and well-tolerated. However, the researchers also observed some Gastrointestinal adverse reactions which occurred early after initiation of treatment and became less frequent with time and typically self-resolved.
FDA has made the following few recommendations concerning safety aspects:
♦Berotralstat shows a QT prolongation on a dose higher than recommended (150 mg).
♦The most common adverse reactions were Gastrointestinal related.
♦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 (eg, cyclosporine).
♦Appropriate monitoring and dose titration is recommended when co-administration of berotralstat with P-gp substrates and drugs with a narrow therapeutic index which are metabolised by CYP2D6 or CYP3A4 enzyme.
♦Due to lack of clinical data FDA doesn't recommend its use for pregnant women, lactating mothers and pediatric patients <12 years.
"Patients and physicians acknowledge that HAE treatments can add a burden to patients' lives. As an oral, once-daily option, ORLADEYO can provide significant attack reduction and lessen the burden associated with injections and infusions," said Marc Riedl, M.D., professor of medicine and clinical director, U.S. Hereditary Angioedema Association Center at the University of California, San Diego, and an investigator in the APeX-2 trial.
"The FDA approval of ORLADEYO fulfils a promise BioCryst made to HAE patients that we were committed to helping them achieve the dream of an oral, once-daily medicine to prevent and reduce the burden of their attacks," said Jon Stonehouse, president and chief executive officer of BioCryst.For further information: