NEW HAVEN, CT, USA I April 06, 2017 I Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced initiation of patient dosing in a Phase 2 open-label study of ACH-4471, Achillion’s first orally-administered, small molecule factor D inhibitor, for patients with paroxysmal nocturnal hemoglobinuria (PNH). This proof of concept study will assess the efficacy, safety, and pharmacokinetics of ACH-4471 in untreated patients with PNH.
“We are pleased to have begun this trial in PNH patients to evaluate ACH-4471, the first orally-administered factor D inhibitor to have demonstrated complement alternative pathway (AP) inhibition in humans, which represents a potentially novel and unique mechanistic approach to treating this life-threatening disease,” commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion.
“As an oral, small molecule inhibitor of factor D, ACH-4471 has a unique mechanism of action to address the needs of PNH patients. By blocking the amplification loop of the complement alternative pathway, ACH-4471 has the potential to control intravascular hemolysis as well as prevent the development of extravascular hemolysis,” said Professor Peter Browett, BMedSci, MBChB, FRACP, FRCPA; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
The primary objective of the study is to assess the change-from-baseline in serum lactate dehydrogenase (LDH) levels, a sensitive biomarker for intravascular hemolysis, during 28 days of dosing. The protocol allows for intra-patient dose-escalation with patients initially receiving 100 mg three times daily of ACH-4471 with the ability to increase dosage during the treatment period. Secondary endpoints being assessed include changes in hemoglobin and red blood cell levels, complement pathway biomarkers, such as Bb and factor D, levels, pharmacokinetics, and safety. Interim results from this study are anticipated during the second quarter of 2017.
David Apelian, M.D., Ph.D., Chief Medical Officer, commented, “In addition to PNH, we look forward to evaluating ACH-4471 in a Phase 2 trial for patients with C3 glomerulopathy, a disease due to over activation of the AP, that we plan initiate during the second half of this year. Furthermore, as we continue to evaluate the PK/PD profile of ACH-4471, we are also pursuing extended release formulations that have the potential of achieving desired exposures with less frequent dosing, potentially just once daily.”
Further information on this study can be found on www.clinicaltrials.gov. Study identifier NCT03053102.
About Achillion’s Complement Alternative Pathway (AP) Factor D Inhibitor Platform
Achillion has leveraged its internal discovery capabilities and a novel complement-related platform to develop small molecule factor D inhibitor compounds that target the complement AP. Factor D is an essential serine protease involved in the AP, a part of the innate immune system. Achillion’s complement platform is focused on seeking to advance small molecule compounds that inhibit factor D and can potentially be used in the treatment of immune-related diseases in which the AP plays a critical role. Potential indications currently being evaluated for these compounds include paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy (C3G), and geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD).
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is thought to be caused by a mutation resulting in the absence of receptors normally present on red blood cells (RBCs) that interact with the AP. The AP of the complement system typically functions normally in these patients but due to the lack of key receptors, known as CD55 and CD59, on the surface of PNH RBCs, the AP treats these cells as foreign and destroys them via hemolysis in the circulatory system (intravascular) and in the liver or spleen (extravascular). Complement factor D is a critical protein within the amplification loop of the AP and it is believed that inhibiting it could control the AP response. Furthermore, this mechanism of action represents a potentially distinct and unique therapeutic approach for controlling intravascular and extravascular hemolysis associated with PNH.
About Achillion Pharmaceuticals
Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) is a science-driven, patient-focused company seeking to leverage its strengths across the continuum from discovery to commercialization in its goal of providing better treatments for people with serious diseases. The company employs a highly-disciplined discovery and development approach that has allowed it to pursue best-in-class oral antiviral therapy for chronic hepatitis C (HCV) and build a platform of potent and specific complement factor D inhibitors for AP-mediated diseases. Achillion is rapidly advancing its efforts to become a fully-integrated pharmaceutical company with a goal of bringing life-saving medicines to patients with rare diseases. More information is available at http://www.achillion.com.
SOURCE: Achillion Pharmaceuticals
Post Views: 236
NEW HAVEN, CT, USA I April 06, 2017 I Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced initiation of patient dosing in a Phase 2 open-label study of ACH-4471, Achillion’s first orally-administered, small molecule factor D inhibitor, for patients with paroxysmal nocturnal hemoglobinuria (PNH). This proof of concept study will assess the efficacy, safety, and pharmacokinetics of ACH-4471 in untreated patients with PNH.
“We are pleased to have begun this trial in PNH patients to evaluate ACH-4471, the first orally-administered factor D inhibitor to have demonstrated complement alternative pathway (AP) inhibition in humans, which represents a potentially novel and unique mechanistic approach to treating this life-threatening disease,” commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion.
“As an oral, small molecule inhibitor of factor D, ACH-4471 has a unique mechanism of action to address the needs of PNH patients. By blocking the amplification loop of the complement alternative pathway, ACH-4471 has the potential to control intravascular hemolysis as well as prevent the development of extravascular hemolysis,” said Professor Peter Browett, BMedSci, MBChB, FRACP, FRCPA; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
The primary objective of the study is to assess the change-from-baseline in serum lactate dehydrogenase (LDH) levels, a sensitive biomarker for intravascular hemolysis, during 28 days of dosing. The protocol allows for intra-patient dose-escalation with patients initially receiving 100 mg three times daily of ACH-4471 with the ability to increase dosage during the treatment period. Secondary endpoints being assessed include changes in hemoglobin and red blood cell levels, complement pathway biomarkers, such as Bb and factor D, levels, pharmacokinetics, and safety. Interim results from this study are anticipated during the second quarter of 2017.
David Apelian, M.D., Ph.D., Chief Medical Officer, commented, “In addition to PNH, we look forward to evaluating ACH-4471 in a Phase 2 trial for patients with C3 glomerulopathy, a disease due to over activation of the AP, that we plan initiate during the second half of this year. Furthermore, as we continue to evaluate the PK/PD profile of ACH-4471, we are also pursuing extended release formulations that have the potential of achieving desired exposures with less frequent dosing, potentially just once daily.”
Further information on this study can be found on www.clinicaltrials.gov. Study identifier NCT03053102.
About Achillion’s Complement Alternative Pathway (AP) Factor D Inhibitor Platform
Achillion has leveraged its internal discovery capabilities and a novel complement-related platform to develop small molecule factor D inhibitor compounds that target the complement AP. Factor D is an essential serine protease involved in the AP, a part of the innate immune system. Achillion’s complement platform is focused on seeking to advance small molecule compounds that inhibit factor D and can potentially be used in the treatment of immune-related diseases in which the AP plays a critical role. Potential indications currently being evaluated for these compounds include paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy (C3G), and geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD).
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
PNH is thought to be caused by a mutation resulting in the absence of receptors normally present on red blood cells (RBCs) that interact with the AP. The AP of the complement system typically functions normally in these patients but due to the lack of key receptors, known as CD55 and CD59, on the surface of PNH RBCs, the AP treats these cells as foreign and destroys them via hemolysis in the circulatory system (intravascular) and in the liver or spleen (extravascular). Complement factor D is a critical protein within the amplification loop of the AP and it is believed that inhibiting it could control the AP response. Furthermore, this mechanism of action represents a potentially distinct and unique therapeutic approach for controlling intravascular and extravascular hemolysis associated with PNH.
About Achillion Pharmaceuticals
Achillion Pharmaceuticals, Inc. (NASDAQ:ACHN) is a science-driven, patient-focused company seeking to leverage its strengths across the continuum from discovery to commercialization in its goal of providing better treatments for people with serious diseases. The company employs a highly-disciplined discovery and development approach that has allowed it to pursue best-in-class oral antiviral therapy for chronic hepatitis C (HCV) and build a platform of potent and specific complement factor D inhibitors for AP-mediated diseases. Achillion is rapidly advancing its efforts to become a fully-integrated pharmaceutical company with a goal of bringing life-saving medicines to patients with rare diseases. More information is available at http://www.achillion.com.
SOURCE: Achillion Pharmaceuticals
Post Views: 236
