– Ongoing Phase 3 study demonstrated PK non-inferiority of ULTOMIRIS SC versus ULTOMIRIS IV at Day 71 –
– Preliminary safety data consistent with the known safety profile of ULTOMIRIS –
BOSTON, MA, USA I June 24, 2020 I Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced topline results from a Phase 3 study of weekly self-administered subcutaneous (SC) ULTOMIRIS® (ravulizumab-cwvz) in adults with paroxysmal nocturnal hemoglobinuria (PNH). The ongoing study met its primary objective of pharmacokinetic (PK)-based non-inferiority of ULTOMIRIS SC versus intravenous (IV) ULTOMIRIS at Day 71. Pending completion of the study, including collection of 12-month safety data as agreed to with the U.S. Food and Drug Administration (FDA), Alexion now expects to file for approval in the U.S. and E.U. for the ULTOMIRIS SC formulation and device combination in PNH and atypical hemolytic uremic syndrome (aHUS) in the third quarter of 2021.
“These data demonstrate that subcutaneous ULTOMIRIS may offer the same benefits of immediate, complete and sustained complement inhibition as the intravenous formulation, while also providing an additional treatment choice for those who would rather self-administer their medicine,” said John Orloff, M.D., Executive Vice President and Head of Research and Development at Alexion. “Delivered via a rapid, patient-friendly delivery device, subcutaneous ULTOMIRIS is an example of Alexion’s continued commitment to innovating for patients. It has the potential to be the first subcutaneous treatment option for both PNH and aHUS and may also offer improved quality of life for patients.”
About the Phase 3 Study
This ongoing global Phase 3, randomized, open-label, parallel-group, multicenter study is evaluating ULTOMIRIS SC compared with ULTOMIRIS IV. The study enrolled 136 adults with PNH who are clinically stable and have previously been treated with SOLIRIS® (eculizumab) for at least three months prior to study entry. The study’s primary objective is to evaluate PK noninferiority of ULTOMIRIS SC compared with ULTOMIRIS IV, as assessed by ULTOMIRIS serum trough concentration at Day 71. The study remains ongoing to assess secondary endpoints, including safety, immunogenicity and various PK/PD, quality of life, device performance and efficacy measures.
Patients were stratified by weight groups (≥ 40 to < 60 kg and ≥ 60 to < 100 kg) and then randomized 2:1 to receive either ULTOMIRIS SC or ULTOMIRIS IV. All patients received an initial IV loading dose on Day 1. On Day 15, patients in the ULTOMIRIS SC group began receiving a once-weekly self-administered fixed-dose of ULTOMIRIS SC, and patients in the ULTOMIRIS IV group received a single infusion of the approved weight-based IV dose.
The study met its primary objective, with ULTOMIRIS SC demonstrating PK-based non-inferiority versus ULTOMIRIS IV at Day 71 (p < 0.0001 for non-inferiority in serum ULTOMIRIS trough concentration – Ctrough). Serum free C5 concentrations were maintained below the target threshold in all patients, and mean lactate dehydrogenase levels remained stable below the upper limit of normal. Preliminary safety data through the 71-day randomized treatment period of the study were consistent with the known safety profile of ULTOMIRIS and did not result in any unexpected safety findings. No adverse events led to withdrawal of study drug in either arm. No serious adverse device effects or meningococcal cases were reported, and no anti-drug antibodies were observed.
Of the 135 patients who completed the randomized controlled treatment portion of the study, all but one participant chose to continue in the ongoing SC-only extension period, where all patients are receiving weekly ULTOMIRIS SC for up to an additional 182 weeks. The extension period will provide 12 months of safety data required for regulatory submissions to applicable health authorities, now anticipated in the third quarter of 2021 to accommodate all regulatory requirements for this combination device filing.
About ULTOMIRIS SC Delivery
Each weekly dose of ULTOMIRIS SC is delivered via two specifically designed, patient-friendly devices that adhere to the body and can be self-administered with the push of a button. The devices can be used either concurrently or sequentially, and when administered concurrently, a full dose of ULTOMIRIS SC can be delivered hands-free in approximately 10 minutes. Previously approved by the FDA for use with another therapy, the single-use SmartDose® device contains a pre-filled cartridge and was developed in collaboration with West Pharmaceutical Services, Inc. to provide patients with a more flexible ULTOMIRIS treatment option.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a serious ultra-rare blood disorder with devastating consequences. It is characterized by the destruction of red blood cells, which is also referred to as hemolysis. PNH occurs when the complement system—a part of the body’s immune system—over-responds, leading the body to attack its own red blood cells. PNH often goes unrecognized, with delays in diagnosis from one to more than five years. Patients with PNH may experience a range of symptoms, such as fatigue, difficulty swallowing, shortness of breath, abdominal pain, erectile dysfunction, dark-colored urine and anemia. The most devastating consequence of chronic hemolysis is the formation of blood clots, which can occur in blood vessels throughout the body, damage vital organs, and potentially lead to premature death. PNH can strike men and women of all races, backgrounds and ages without warning, with an average age of onset in the early 30s.
About Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease that can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots. Atypical HUS occurs when the complement system—a part of the body’s immune system—over-responds, leading the body to attack its own healthy cells. Atypical HUS can cause sudden organ failure or a slow loss of function over time—potentially resulting in the need for a transplant, and in some cases, death. Atypical HUS affects both adults and children, and many patients present in critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of aHUS can be poor in many cases, so a timely and accurate diagnosis—in addition to treatment—is critical to improving patient outcomes. Available tests can help distinguish aHUS from other hemolytic diseases with similar symptoms.
About ULTOMIRIS® (ravulizumab‑cwvz)
ULTOMIRIS® (ravulizumab-cwvz) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks or every four weeks for pediatric patients less than 20 kg, following a loading dose. ULTOMIRIS is approved in the United States (U.S.), European Union (EU) and Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH) and in the U.S. for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients.
U.S. INDICATIONS & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS (ravulizumab-cwvz) 300 mg / 30 mL injection for intravenous use
U.S. INDICATIONS
ULTOMIRIS is a prescription medicine called a monoclonal antibody. ULTOMIRIS is used to treat adults with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH). ULTOMIRIS is used to treat adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). It is not known if ULTOMIRIS is safe and effective in children with PNH. It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age.
Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.
About Alexion
Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare and devastating diseases through the discovery, development and commercialization of life-changing medicines. As the global leader in complement biology and inhibition for more than 20 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D). In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, metabolic disorders and cardiology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: www.alexion.com.
SOURCE: Alexion Pharmaceuticals
Post Views: 122
– Ongoing Phase 3 study demonstrated PK non-inferiority of ULTOMIRIS SC versus ULTOMIRIS IV at Day 71 –
– Preliminary safety data consistent with the known safety profile of ULTOMIRIS –
BOSTON, MA, USA I June 24, 2020 I Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced topline results from a Phase 3 study of weekly self-administered subcutaneous (SC) ULTOMIRIS® (ravulizumab-cwvz) in adults with paroxysmal nocturnal hemoglobinuria (PNH). The ongoing study met its primary objective of pharmacokinetic (PK)-based non-inferiority of ULTOMIRIS SC versus intravenous (IV) ULTOMIRIS at Day 71. Pending completion of the study, including collection of 12-month safety data as agreed to with the U.S. Food and Drug Administration (FDA), Alexion now expects to file for approval in the U.S. and E.U. for the ULTOMIRIS SC formulation and device combination in PNH and atypical hemolytic uremic syndrome (aHUS) in the third quarter of 2021.
“These data demonstrate that subcutaneous ULTOMIRIS may offer the same benefits of immediate, complete and sustained complement inhibition as the intravenous formulation, while also providing an additional treatment choice for those who would rather self-administer their medicine,” said John Orloff, M.D., Executive Vice President and Head of Research and Development at Alexion. “Delivered via a rapid, patient-friendly delivery device, subcutaneous ULTOMIRIS is an example of Alexion’s continued commitment to innovating for patients. It has the potential to be the first subcutaneous treatment option for both PNH and aHUS and may also offer improved quality of life for patients.”
About the Phase 3 Study
This ongoing global Phase 3, randomized, open-label, parallel-group, multicenter study is evaluating ULTOMIRIS SC compared with ULTOMIRIS IV. The study enrolled 136 adults with PNH who are clinically stable and have previously been treated with SOLIRIS® (eculizumab) for at least three months prior to study entry. The study’s primary objective is to evaluate PK noninferiority of ULTOMIRIS SC compared with ULTOMIRIS IV, as assessed by ULTOMIRIS serum trough concentration at Day 71. The study remains ongoing to assess secondary endpoints, including safety, immunogenicity and various PK/PD, quality of life, device performance and efficacy measures.
Patients were stratified by weight groups (≥ 40 to < 60 kg and ≥ 60 to < 100 kg) and then randomized 2:1 to receive either ULTOMIRIS SC or ULTOMIRIS IV. All patients received an initial IV loading dose on Day 1. On Day 15, patients in the ULTOMIRIS SC group began receiving a once-weekly self-administered fixed-dose of ULTOMIRIS SC, and patients in the ULTOMIRIS IV group received a single infusion of the approved weight-based IV dose.
The study met its primary objective, with ULTOMIRIS SC demonstrating PK-based non-inferiority versus ULTOMIRIS IV at Day 71 (p < 0.0001 for non-inferiority in serum ULTOMIRIS trough concentration – Ctrough). Serum free C5 concentrations were maintained below the target threshold in all patients, and mean lactate dehydrogenase levels remained stable below the upper limit of normal. Preliminary safety data through the 71-day randomized treatment period of the study were consistent with the known safety profile of ULTOMIRIS and did not result in any unexpected safety findings. No adverse events led to withdrawal of study drug in either arm. No serious adverse device effects or meningococcal cases were reported, and no anti-drug antibodies were observed.
Of the 135 patients who completed the randomized controlled treatment portion of the study, all but one participant chose to continue in the ongoing SC-only extension period, where all patients are receiving weekly ULTOMIRIS SC for up to an additional 182 weeks. The extension period will provide 12 months of safety data required for regulatory submissions to applicable health authorities, now anticipated in the third quarter of 2021 to accommodate all regulatory requirements for this combination device filing.
About ULTOMIRIS SC Delivery
Each weekly dose of ULTOMIRIS SC is delivered via two specifically designed, patient-friendly devices that adhere to the body and can be self-administered with the push of a button. The devices can be used either concurrently or sequentially, and when administered concurrently, a full dose of ULTOMIRIS SC can be delivered hands-free in approximately 10 minutes. Previously approved by the FDA for use with another therapy, the single-use SmartDose® device contains a pre-filled cartridge and was developed in collaboration with West Pharmaceutical Services, Inc. to provide patients with a more flexible ULTOMIRIS treatment option.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a serious ultra-rare blood disorder with devastating consequences. It is characterized by the destruction of red blood cells, which is also referred to as hemolysis. PNH occurs when the complement system—a part of the body’s immune system—over-responds, leading the body to attack its own red blood cells. PNH often goes unrecognized, with delays in diagnosis from one to more than five years. Patients with PNH may experience a range of symptoms, such as fatigue, difficulty swallowing, shortness of breath, abdominal pain, erectile dysfunction, dark-colored urine and anemia. The most devastating consequence of chronic hemolysis is the formation of blood clots, which can occur in blood vessels throughout the body, damage vital organs, and potentially lead to premature death. PNH can strike men and women of all races, backgrounds and ages without warning, with an average age of onset in the early 30s.
About Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease that can cause progressive injury to vital organs, primarily the kidneys, via damage to the walls of blood vessels and blood clots. Atypical HUS occurs when the complement system—a part of the body’s immune system—over-responds, leading the body to attack its own healthy cells. Atypical HUS can cause sudden organ failure or a slow loss of function over time—potentially resulting in the need for a transplant, and in some cases, death. Atypical HUS affects both adults and children, and many patients present in critical condition, often requiring supportive care, including dialysis, in an intensive care unit. The prognosis of aHUS can be poor in many cases, so a timely and accurate diagnosis—in addition to treatment—is critical to improving patient outcomes. Available tests can help distinguish aHUS from other hemolytic diseases with similar symptoms.
About ULTOMIRIS® (ravulizumab‑cwvz)
ULTOMIRIS® (ravulizumab-cwvz) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks or every four weeks for pediatric patients less than 20 kg, following a loading dose. ULTOMIRIS is approved in the United States (U.S.), European Union (EU) and Japan as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH) and in the U.S. for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA) in adult and pediatric (one month of age and older) patients.
U.S. INDICATIONS & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS (ravulizumab-cwvz) 300 mg / 30 mL injection for intravenous use
U.S. INDICATIONS
ULTOMIRIS is a prescription medicine called a monoclonal antibody. ULTOMIRIS is used to treat adults with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH). ULTOMIRIS is used to treat adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). It is not known if ULTOMIRIS is safe and effective in children with PNH. It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age.
Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.
About Alexion
Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare and devastating diseases through the discovery, development and commercialization of life-changing medicines. As the global leader in complement biology and inhibition for more than 20 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as well as the first and only approved complement inhibitor to treat anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D). In addition, the company is developing several mid-to-late-stage therapies, including a copper-binding agent for Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D inhibitor as well as several early-stage therapies, including one for light chain (AL) amyloidosis, a second oral Factor D inhibitor and a third complement inhibitor. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, metabolic disorders and cardiology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries. This press release and further information about Alexion can be found at: www.alexion.com.
SOURCE: Alexion Pharmaceuticals
Post Views: 122
