Date: 2015-06-12
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 20th Congress of the European Hematology Association, in Vienna, Austria
Company: Prothena (Ireland)
Product: NEOD001
Action
mechanism: monoclonal antibody. NEOD001 is a humanized monoclonal antibody that specifically targets the circulating soluble amyloid and deposited insoluble amyloid that accumulates in both the AL and AA forms of amyloidosis. The ongoing multi-center Phase 1/2 clinical trial is evaluating the safety, tolerability, pharmacokinetics and immunogenicity of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction. The study is also evaluating exploratory biomarkers for cardiac and renal function. Separately, The VITAL Amyloidosis Study, a double-blind, placebo-controlled, global Phase 3 registrational trial, will evaluate NEOD001 in newly-diagnosed, treatment-naive patients with AL amyloidosis, and will assess all-cause mortality and cardiac hospitalizations in addition to biomarker, functional and quality of life endpoints.
Disease: AL amyloidosis or primary amyloidosis
Therapeutic area: Rare diseases
Country: USA
Trial
details: The study is a dose escalation study to determine the maximum tolerated dose of NEOD001 in approximately 30 subjects with AL amyloidosis. Expansion phase to evaluate safety, efficacy and pharmacokinetics of NEOD001 in 25 additional subjects at the maximum tolerated dose. (NCT01707264).
Latest
news: * On June 12, 2015, Prothena, a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapy programs,announced that Dr. Michaela Liedtke of Stanford University School of Medicine presented data from the ongoing Phase 1/2 trial of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction in an oral presentation (Abstract #S104) during the 20th Congress of the European Hematology Association (EHA) in Vienna. Initially presented in an oral session by Dr. Morie A. Gertz of the Mayo Clinic at the 2015 American Society of Clinical Oncology Annual Meeting earlier this month, the clinical data from the multiple ascending dose portion of Prothena\'s ongoing Phase 1/2 trial of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction demonstrated improvements in clinical biomarker activity with additional monthly infusions of NEOD001. Cardiac-evaluable and renal-evaluable patients achieved best response rates of 57.1% and 60.0%, respectively. NEOD001 was safe and well tolerated. Renal and Cardiac Biomarker Responses in NEOD001 Phase 1/2 Study: In a best response analysis, nine of 15 renal-evaluable patients (60.0%) treated with NEOD001 demonstrated a renal response, defined as a 30.0% decrease in proteinuria in the absence of estimated glomerular filtration rate (eGFR) worsening, and the remaining six patients (40.0%) achieved stable disease. The 60.0% renal best response rate is more than double the expected renal best response rate of approximately 24% from historical data in patients treated solely with off-label standard of care (Palladini, et al., Blood. 2014 124: 2325-2332). Increased levels of proteinuria and decreased eGFR predict faster progression to dialysis whereas decreased levels of proteinuria and increased eGFR predict delayed time to dialysis. In a best response analysis, eight of 14 cardiac-evaluable patients (57.1%) treated with NEOD001 demonstrated a cardiac response, defined as more than 30.0% and 300 pg/mL decrease in levels of NT-proBNP (an established cardiac biomarker that is predictive of mortality in patients with AL amyloidosis), and the remaining six patients (42.9%) achieved stable disease. Also, additional monthly infusions of NEOD001 were observed to be significantly correlated with NT-proBNP decline (p<0.0001). The 57.1% cardiac best response rate is more than double the expected cardiac best response rate of 26.5% from historical data in patients treated solely with off-label standard of care (Comenzo, et al., Leukemia. 2012;26:2317--2325). As noted in numerous peer-reviewed publications, increasing levels of NT-proBNP predict higher mortality rates in patients with AL amyloidosis. Conversely, decreasing levels of NT-proBNP following intervention predict lower mortality rates. Mechanism of Action: The clinical results demonstrated in this study to date expand on more than a decade of amyloid research by Prothena. The most recent results are consistent with the proposed mechanism of action demonstrating that NEOD001 functions in two ways: neutralization of circulating soluble amyloid and clearance of deposited insoluble amyloid within affected organs. The Phase 1/2 data continued to support that NEOD001 acts as a disease-modifying agent in AL amyloidosis, distinct from current off-label standard of care therapies that solely attempt to reduce the production of newly produced immunoglobulin light chains and often result in serious side effects, without directly clearing the residual amyloid. Safety, Tolerability, Pharmacokinetics and Immunogenicity: Data from the Phase 1/2 study continued to demonstrate that monthly infusions (every 28 days) of NEOD001 are safe and well-tolerated in patients with AL amyloidosis and persistent organ dysfunction. An interim analysis as of February 28, 2015 showed that a total of 27 patients in seven dosing cohorts received 327 infusions, with an average treatment duration of 12 months. No hypersensitivity reactions or drug-related serious adverse events were reported and no anti-NEOD001 antibodies were detected. NEOD001 also continued to demonstrate excellent pharmacokinetic properties, supporting a dose level of 24 mg/kg on a 28 day cycle. The most frequently reported treatment-emergent adverse events (more than 10% of subjects) were fatigue, upper respiratory tract infection, cough, dyspnea, headache, anemia, increased blood creatinine, edema, diarrhea, nausea and hyponatremia. No dose limiting toxicities were observed and no patient discontinued treatment due to drug-related adverse events. All patients remaining in the study escalated to 24 mg/kg as of December 2, 2014.
