Investigational Monoclonal Antibody Granted U.S. FDA Orphan Drug Designation
HATTERSHEIM, Germany I June 8, 2020 ICSL Behring, a global biotherapeutics leader, today announced results of a Phase 2 clinical trial for garadacimab (previously known as CSL312), an investigational novel Factor XIIa-inhibitory monoclonal antibody (FXIIa mAb) in development as a preventive treatment in hereditary angioedema (HAE). The data, presented at the European Academy of Allergy and Clinical Immunology (EAACI) Digital Congress 2020, showed that the study met its primary endpoint, demonstrating reduced number of attacks compared to placebo in patients with HAE. Mean percentage reductions were 88.68%, 98.94%, and 90.50% in three garadacimab groups – 75, 200, and 600 mg subcutaneous (SC) – versus placebo. The study also showed garadacimab to be well-tolerated. HAE is a rare, genetic and potentially life-threatening condition that causes painful, debilitating and unpredictable episodes of swelling of the abdomen, larynx, face and extremities, among other areas of the body. Garadacimab inhibits the plasma protein, FXIIa. FXIIa initiates the cascade of events that lead to edema formation. By targeting FXIIa, garadacimab can prevent the initiation of this cascade.
Additionally, last month, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to garadacimab as an investigational therapy for the prevention of bradykinin-mediated angioedema, which includes both hereditary and non-hereditary (acquired) angioedema. The FDA Office of Orphan Products Development (OOPD) grants orphan drug designation to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 U.S. patients. The designation qualifies companies with a range of incentives, including the potential for marketing exclusivity upon approval.
“The attacks that HAE patients experience can be very frightening, and clinicians want to do anything in their power to reduce the frequency of these attacks, lessen the need for rescue medicine and simplify treatment,” said lead study investigator Timothy Craig, D.O., Allergy, Asthma and Immunology, Department of Medicine and Pediatrics, Penn State Hershey, Hershey, PA. “The findings of this study are very encouraging and we look forward to further research assessing the safety and efficacy of garadacimab.”
Affecting about one in 40,000-50,000 people globally, attacks of HAE can happen suddenly and with little warning. Many people with HAE need both preventive treatment as well as on-demand (or “rescue”) therapies to treat an attack in progress, both of which are associated with frequent dosing.
“Consistent with our more than 40-year commitment to HAE therapeutic innovation, garadacimab represents a potentially first-in-class agent that utilizes a unique approach as a preventive treatment in HAE,” said Mittie Doyle, M.D., Vice President, Research and Development, Immunology Therapeutic Area at CSL Behring. “We are encouraged by the promising garadacimab data as well as the orphan drug designation milestone and look forward to advancing the clinical program to continue to deliver on our promise and improve the lives of people living with HAE.”
About the Phase 2 Study
In the Phase 2 study, a total of 32 adults with HAE were randomized and received either garadacimab (either 75 mg, 200 mg or 600 mg) or placebo every four weeks for 12 weeks. Researchers observed the following:
- Significantly fewer monthly attacks in all three groups taking garadacimab, with garadacimab reducing the mean attack rates by 88.68%, 98.94% and 90.50%, respectively, compared to placebo. Specifically, the monthly attack rates were 0.48, 0.05 and 0.40 for the three doses of garadacimab compared to 4.24 for placebo. As comparison, patients experienced a mean monthly attack rate of 5.17 prior to the start of the study.
- A large portion of patients taking garadacimab were attack-free during the course of the study. Specifically, 55.56%, 87.5% and 42.86% of patients taking garadacimab, respectively, did not have any attacks compared to zero percent in the placebo group.
- All adverse events were mild or moderate, with the percentage of patients experiencing at least one treatment-emergent adverse event (TEAE) being similar across all groups. The common TEAE was mild to moderate injection site erythema (12.5%).
Additional Study Details
This multicenter, randomized, double-blind, placebo-controlled, parallel-arm Phase 2 study (NCT03712228) examined the efficacy, safety and pharmacokinetics of three different doses of garadacimab, an novel investigational FXIIa mAb, compared to placebo for the preventive treatment of HAE. Enrolled patients were 18-65 years of age with type I or type II HAE, with four or more documented attacks over a consecutive two-month period during the three months prior to screening. Patients were randomized to receive either garadacimab 75 mg (n=9), garadacimab 200 mg (n=8), garadacimab 600 mg (n=7) or placebo (n=8), which were given as a subcutaneous injection every four weeks for 12 weeks after an intravenous loading dose. The primary endpoint was the number of attacks. Secondary endpoints included the reduction in attacks compared with the run-in period (4 or up to 8 weeks prior to the start of treatment) or placebo, use of on-demand therapies (to treat an attack) per month and safety.
About Hereditary Angioedema
A rare, genetic and potentially life-threatening condition, HAE causes painful, debilitating and unpredictable episodes of swelling of the abdomen, larynx, face and extremities, among other areas of the body. HAE is one of two forms of bradykinin-mediated angioedema, the other being nonhereditary or acquired angioedema. HAE is caused by deficient or dysfunctional C1-INH, a protein in the blood that helps to control inflammation. The defect with C1-INH lies within a person’s genetic code, which is why HAE runs in families. HAE is classified as either type I, type II or C1-n (previously known as type III), which is HAE with normal C1-INH levels.
More on Garadacimab
Garadacimab is a novel Factor XIIa-inhibitory monoclonal antibody (FXIIa mAb) currently in Phase 2 clinical development as a new type of once-monthly subcutaneous prophylactic treatment for attacks related to HAE, a form of bradykinin-mediated angioedema. Garadacimab inhibits the plasma protein, FXIIa. When FXIIa is activated, it initiates the cascade of events leading to edema formation. By targeting FXIIa, garadacimab can prevent the initiation of this cascade. The U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to garadacimab as an investigational therapy for the prevention of bradykinin-mediated angioedema. CSL Behring is also investigating garadacimab for other indications, beyond HAE, where FXIIa inhibition may be a factor in improving clinical outcomes.
About CSL Behring
CSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients’ needs by using the latest technologies, the company develops and delivers innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, respiratory disease, and neurological disorders. The company’s products are also used in cardiac surgery, burn treatment and to prevent hemolytic disease of the newborn.
CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX:CSL;USOTC:CSLLY), headquartered in Melbourne, Australia, employs more than 26,000 people worldwide, and delivers its life-saving therapies to people in more than 70 countries. For inspiring stories about the promise of biotechnology, visit Vita at CSLBehring.com/vita and follow us on Twitter.com/CSLBehring.
SOURCE: CSL Behring
Post Views: 339
Investigational Monoclonal Antibody Granted U.S. FDA Orphan Drug Designation
HATTERSHEIM, Germany I June 8, 2020 ICSL Behring, a global biotherapeutics leader, today announced results of a Phase 2 clinical trial for garadacimab (previously known as CSL312), an investigational novel Factor XIIa-inhibitory monoclonal antibody (FXIIa mAb) in development as a preventive treatment in hereditary angioedema (HAE). The data, presented at the European Academy of Allergy and Clinical Immunology (EAACI) Digital Congress 2020, showed that the study met its primary endpoint, demonstrating reduced number of attacks compared to placebo in patients with HAE. Mean percentage reductions were 88.68%, 98.94%, and 90.50% in three garadacimab groups – 75, 200, and 600 mg subcutaneous (SC) – versus placebo. The study also showed garadacimab to be well-tolerated. HAE is a rare, genetic and potentially life-threatening condition that causes painful, debilitating and unpredictable episodes of swelling of the abdomen, larynx, face and extremities, among other areas of the body. Garadacimab inhibits the plasma protein, FXIIa. FXIIa initiates the cascade of events that lead to edema formation. By targeting FXIIa, garadacimab can prevent the initiation of this cascade.
Additionally, last month, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to garadacimab as an investigational therapy for the prevention of bradykinin-mediated angioedema, which includes both hereditary and non-hereditary (acquired) angioedema. The FDA Office of Orphan Products Development (OOPD) grants orphan drug designation to novel drugs or biologics that treat a rare disease or condition affecting fewer than 200,000 U.S. patients. The designation qualifies companies with a range of incentives, including the potential for marketing exclusivity upon approval.
“The attacks that HAE patients experience can be very frightening, and clinicians want to do anything in their power to reduce the frequency of these attacks, lessen the need for rescue medicine and simplify treatment,” said lead study investigator Timothy Craig, D.O., Allergy, Asthma and Immunology, Department of Medicine and Pediatrics, Penn State Hershey, Hershey, PA. “The findings of this study are very encouraging and we look forward to further research assessing the safety and efficacy of garadacimab.”
Affecting about one in 40,000-50,000 people globally, attacks of HAE can happen suddenly and with little warning. Many people with HAE need both preventive treatment as well as on-demand (or “rescue”) therapies to treat an attack in progress, both of which are associated with frequent dosing.
“Consistent with our more than 40-year commitment to HAE therapeutic innovation, garadacimab represents a potentially first-in-class agent that utilizes a unique approach as a preventive treatment in HAE,” said Mittie Doyle, M.D., Vice President, Research and Development, Immunology Therapeutic Area at CSL Behring. “We are encouraged by the promising garadacimab data as well as the orphan drug designation milestone and look forward to advancing the clinical program to continue to deliver on our promise and improve the lives of people living with HAE.”
About the Phase 2 Study
In the Phase 2 study, a total of 32 adults with HAE were randomized and received either garadacimab (either 75 mg, 200 mg or 600 mg) or placebo every four weeks for 12 weeks. Researchers observed the following:
- Significantly fewer monthly attacks in all three groups taking garadacimab, with garadacimab reducing the mean attack rates by 88.68%, 98.94% and 90.50%, respectively, compared to placebo. Specifically, the monthly attack rates were 0.48, 0.05 and 0.40 for the three doses of garadacimab compared to 4.24 for placebo. As comparison, patients experienced a mean monthly attack rate of 5.17 prior to the start of the study.
- A large portion of patients taking garadacimab were attack-free during the course of the study. Specifically, 55.56%, 87.5% and 42.86% of patients taking garadacimab, respectively, did not have any attacks compared to zero percent in the placebo group.
- All adverse events were mild or moderate, with the percentage of patients experiencing at least one treatment-emergent adverse event (TEAE) being similar across all groups. The common TEAE was mild to moderate injection site erythema (12.5%).
Additional Study Details
This multicenter, randomized, double-blind, placebo-controlled, parallel-arm Phase 2 study (NCT03712228) examined the efficacy, safety and pharmacokinetics of three different doses of garadacimab, an novel investigational FXIIa mAb, compared to placebo for the preventive treatment of HAE. Enrolled patients were 18-65 years of age with type I or type II HAE, with four or more documented attacks over a consecutive two-month period during the three months prior to screening. Patients were randomized to receive either garadacimab 75 mg (n=9), garadacimab 200 mg (n=8), garadacimab 600 mg (n=7) or placebo (n=8), which were given as a subcutaneous injection every four weeks for 12 weeks after an intravenous loading dose. The primary endpoint was the number of attacks. Secondary endpoints included the reduction in attacks compared with the run-in period (4 or up to 8 weeks prior to the start of treatment) or placebo, use of on-demand therapies (to treat an attack) per month and safety.
About Hereditary Angioedema
A rare, genetic and potentially life-threatening condition, HAE causes painful, debilitating and unpredictable episodes of swelling of the abdomen, larynx, face and extremities, among other areas of the body. HAE is one of two forms of bradykinin-mediated angioedema, the other being nonhereditary or acquired angioedema. HAE is caused by deficient or dysfunctional C1-INH, a protein in the blood that helps to control inflammation. The defect with C1-INH lies within a person’s genetic code, which is why HAE runs in families. HAE is classified as either type I, type II or C1-n (previously known as type III), which is HAE with normal C1-INH levels.
More on Garadacimab
Garadacimab is a novel Factor XIIa-inhibitory monoclonal antibody (FXIIa mAb) currently in Phase 2 clinical development as a new type of once-monthly subcutaneous prophylactic treatment for attacks related to HAE, a form of bradykinin-mediated angioedema. Garadacimab inhibits the plasma protein, FXIIa. When FXIIa is activated, it initiates the cascade of events leading to edema formation. By targeting FXIIa, garadacimab can prevent the initiation of this cascade. The U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to garadacimab as an investigational therapy for the prevention of bradykinin-mediated angioedema. CSL Behring is also investigating garadacimab for other indications, beyond HAE, where FXIIa inhibition may be a factor in improving clinical outcomes.
About CSL Behring
CSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients’ needs by using the latest technologies, the company develops and delivers innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, respiratory disease, and neurological disorders. The company’s products are also used in cardiac surgery, burn treatment and to prevent hemolytic disease of the newborn.
CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX:CSL;USOTC:CSLLY), headquartered in Melbourne, Australia, employs more than 26,000 people worldwide, and delivers its life-saving therapies to people in more than 70 countries. For inspiring stories about the promise of biotechnology, visit Vita at CSLBehring.com/vita and follow us on Twitter.com/CSLBehring.
SOURCE: CSL Behring
Post Views: 339
