Rare Disease Report

Phase 3 Trials Planned for Novel AL Amyloidosis Drug NEOD001

FEBRUARY 25, 2015
Christin Melton

NEOD001 is an investigational protein immunotherapy being developed by Prothena Corporation plc to treat AL amyloidosis, a life-threatening hematologic disorder diagnosed in an estimated 3000 people in the United States each year.1 All together, approximately 15,000 people in Europe and the United States are living with the disease.2 The exact number of affected individuals is difficult to determine because diagnosis is often delayed or overlooked.

AL amyloidosis, also known as primary systemic amyloidosis, is the most common form of systemic amyloidosis and accounts for approximately 70% of all cases. AL amyloidosis involves a clonal population of plasma cells in the bone marrow that begin to proliferate abnormally and overproduce light chain proteins. Normally, light chains pair up with heavy chains to form immunoglobulins, and excess light chains make their way into the bloodstream where they circulate as free light chains (FLCs). In AL amyloidosis, these FLCs are misfolded and aggregate into amyloid fibrils that accumulate in tissues, predominantly in the heart and kidneys. The toxic effects of these fibril deposits cause organ dysfunction, organ failure, and, ultimately, death. No cure exists for AL amyloidosis, and no treatment has ever been approved specifically to treat the disorder.

Standard care is typically a regimen of chemotherapeutic agents approved to treat other conditions.3 Gene Kinney, PhD, chief scientific officer and head of Research and Development at Prothena, explained that the cytotoxic chemotherapy drugs target the aberrant plasma cells responsible for producing the light chains, but they do not address the residual amyloid aggregates built up in the tissues. “In contrast, NEOD001 does not target the plasma cells and is instead designed to target the toxic light chain species that are more proximally responsible for the organ dysfunction and/or failure,” he said. NEOD001 neutralizes and disaggregates soluble amyloid circulating in the bloodstream and induces clearance of the insoluble amyloid deposits in the organs.

“Due to multi-organ involvement, diagnosis of AL amyloidosis is often difficult, delayed, or missed,” Kinney said. As a result, many patients today have already accumulated damaging amounts of toxic amyloid in their organs by the time they undergo chemotherapy to attack the abnormal plasma cells. “NEOD001 is the most advanced therapeutic agent designed to neutralize and clear toxic amyloid to be under active evaluation in clinical trials,” noted Kinney.
In December 2014, investigators reported interim results from a phase 1/2 study of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction that suggested NEOD001 functioned as hypothesized.2 Kinney said biomarker signals observed with NEOD001 therapy were “consistent with positive response and stabilization in approximately 71% of all study patients who were eligible for biomarker assessment.” A best response-analysis of the 14 patients in the study who had elevated baseline levels of NT-proBNP, a cardiac biomarker that correlates positively with mortality risk, showed half achieved a cardiac response and the other half achieved stable disease. In a best response analysis of the 14 renal-evaluable patients, 43% (6/14) had a renal response (a 30% decrease in proteinuria without a worsening glomerular filtration rate), and 57% achieved stable disease. “These results compare favorably to historical studies that have evaluated the effect of plasma cell–directed standard of care treatments,” Kinney said.

In the trial, NEOD001 appeared safe and well tolerated, with no drug-related serious adverse events observed and no dose-limiting toxicities. This is important because patients would need to take NEOD001 continuously to slow or arrest the build-up of toxic amyloid in tissues.

Kinney said the US Food and Drug Administration has granted fast track designation to NEOD001, a status available to drugs that treat serious conditions and fulfill an unmet medical need. “We are excited to have received fast track designation…It permits the company to have early and frequent communications with the FDA in the development and review process, potentially leading to faster drug approval,” he said.
On the basis of positive results from the phase 1/2 study, Prothena is moving forward with the phase 3 VITAL study of NEOD001 (https://clinicaltrials.gov/ct2/show/NCT02312206). The multicenter randomized trial plans to recruit 236 patients with newly diagnosed, untreated AL amyloidosis. “We expect enrollment to take approximately 18 to 30 months, with the last patient in the study followed for an additional 12 to 18 months,” said Kinney. He added that the timing of results would depend partly on accrual.


  1. Amyloidosis Foundation. Primary AL. http://www.amyloidosis.org/TreatmentInformation/primaryAL.html. Accessed February 23, 2015.
  2. Prothena initiates NEOD001 global phase 3 registrational trial based on positive results in ongoing phase 1/2 study of NEOD001 in patients with AL amyloidosis. http://ir.prothena.com/releasedetail.cfm?releaseid=885753. Published December 2, 2014. Accessed February 23, 2015.
  3. Merlini G, Wechalekar AD, Palladini G. Systemic light chain amyloidosis: an update for treating physicians. Blood. 2013;121:5124-5130.
  4. ClinicalTrials.gov. The VITAL amyloidosis study, a phase 3, multicenter efficacy and safety study of NEOD001. https://clinicaltrials.gov/ct2/show/NCT02312206. Updated January 26, 2015. Accessed February 23, 2015.

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