DUBLIN, Ireland, June 12, 2015 (GLOBE NEWSWIRE) -- Prothena Corporation plc (Nasdaq:PRTA), a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapy programs, today 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.
"The clinical results presented today demonstrate that additional monthly infusions of NEOD001 correlate significantly with decreases in both cardiac and renal biomarkers over time. Decreases in cardiac biomarkers predict increased survival and decreases in renal biomarkers predict delayed time to kidney failure," said Michaela Liedtke, MD, Assistant Professor of Medicine at Stanford University. "These maturing positive data provide further support for the evaluation of NEOD001 in The VITAL Amyloidosis Study, a global Phase 3 registrational trial, in newly-diagnosed, treatment-naïve patients with AL amyloidosis."
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.
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-naïve patients with AL amyloidosis, and will assess all-cause mortality and cardiac hospitalizations in addition to biomarker, functional and quality of life endpoints. For more information on both the Phase 1/2 and VITAL Phase 3 trials, please
visit www.clinicaltrials.gov, and search identifiers NCT01707264 (Phase 1/2) and NCT02312206 (VITAL Phase 3).
About AL Amyloidosis
Systemic amyloidoses are a complex group of progressive diseases caused by tissue deposition of misfolded proteins that result in progressive organ damage. The most common type, AL amyloidosis or primary amyloidosis, involves a hematological disorder caused by plasma cells that produce misfolded AL protein resulting in deposits of abnormal AL protein (amyloid) in the tissues and organs of individuals with this disease. There are no approved treatments for AL amyloidosis that directly target potentially toxic forms of the AL protein. AL amyloidosis is a rare disorder and it is estimated that about 30,000 to 45,000 patients in the U.S. and Europe suffer from this disease. Both the causes and origins of AL amyloidosis remain poorly understood. For more information on AL amyloidosis, please visit the websites of the Amyloidosis Support Group and the Amyloidosis Foundation.
Prothena Corporation plc is a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapy programs for the potential treatment of diseases that involve amyloid or cell adhesion. The Company is developing antibody-based product candidates that target a number of potential indications including AL amyloidosis (NEOD001), Parkinson's disease and other related synucleinopathies (PRX002), and psoriasis and other inflammatory diseases (PRX003).
This press release contains forward-looking statements. These statements relate to, among other things, the potential clinical benefits of NEOD001. These statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to the risks, uncertainties and other factors described in the "Risk Factors" sections of our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 13, 2015 and our
subsequent Quarterly Reports on Form 10-Q filed with the SEC. Prothena undertakes no obligation to update publicly any forward-looking statements contained in this press release as a result of new information, future events or changes in Prothena's expectations.