Prothena Reports Results from the Phase 3 VITAL Amyloidosis Study of NEOD001 (birtamimab) in AL Amyloidosis
- Results from final analysis of the composite primary endpoint were consistent with the futility analysis reported in
- Results from post hoc analyses revealed a potential survival benefit with NEOD001 in the category of patients at the highest risk for early mortality (
Mayo Stage IV)
- Exploring potential business development opportunities to advance NEOD001
- Investor conference call and webcast scheduled today at
“We are grateful to patients, their families, investigators and study site staff who made this study, and what we have learned, possible,” said
Phase 3 VITAL Study Results
The Phase 3 VITAL study (N=260) was terminated early based on a futility analysis conducted in
Baseline demographics and characteristics were well-balanced across the NEOD001 and control arms of the study. NEOD001 was generally safe and well tolerated. The NEOD001 and control arms had similar frequencies of treatment emergent adverse events (TEAEs, 98 percent and 100 percent, respectively) and serious adverse events (SAEs, 68 percent and 70 percent, respectively). The most common TEAEs were fatigue, nausea, peripheral edema, constipation and diarrhea, and were similar in both arms. Of the patients with a serious adverse event, 95 percent were considered not related to NEOD001.
Post Hoc Analyses
Post hoc analyses by their nature have an increased potential for type 1 error, meaning there is an increased potential for a false positive finding.
Study termination by sponsor was the primary reason for patient discontinuation, and nearly all (94 percent) occurred after the initial 12 months. Therefore, the initial 12-month study period, because it had the least censoring, was the basis of the modified intent-to-treat (mITT) analyses.
The final hazard ratios, which favored NEOD001 for the composite primary endpoint, were largely attributable to all-cause mortality rather than cardiac hospitalization in both the intent-to-treat (ITT) and mITT analyses.
Further evaluations included analyses by Mayo Staging, which is a prognostic categorization system for mortality risk in newly diagnosed patients. Mayo Staging was utilized as a randomization stratification factor in the Phase 3 VITAL study. Patients in
The mITT analyses of time to all-cause mortality by
The majority (84 percent) of mortality events in the study occurred in the initial 12 months, and of these, approximately half were in
|ITT and mITT (Initial 12-Month Study Period) Results:|
|Composite primary endpoint||0.835 (0.5799, 1.2011)
|0.784 (0.5341, 1.1507)
|All-cause mortality||1.334 (0.7386, 2.4107)
|1.244 (0.6435, 2.4035)
|All-cause mortality||0.544 (0.2738, 1.0826)
|0.498 (0.2404, 1.0304)
|1Composite primary endpoint is time to all-cause mortality or time to cardiac hospitalization more than 90 days after first infusion of study drug
2All-cause mortality regardless of prior cardiac hospitalization
3mITT = initial 12-month study period
4HR < 1.0 favors NEOD001 + SOC / HR > 1.0 favors placebo + SOC
5All p-values other than for the composite primary endpoint for the ITT analysis, are descriptive
Phase 3 VITAL Study Design
The VITAL Amyloidosis Study was a Phase 3 global, multi-center, randomized, double-blind, placebo-controlled clinical study of NEOD001. The study enrolled 260 newly diagnosed, treatment-naïve patients with AL amyloidosis and cardiac dysfunction. Patients were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days, with both arms receiving concurrent standard of care chemotherapy consisting of a first-line bortezomib-containing regimen. Randomization stratification factors were
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About NEOD001 (birtamimab)
NEOD001 is an investigational humanized immunoglobulin G1 designed to directly neutralize soluble toxic aggregates and promote clearance of amyloid via phagocytosis to remove organ-deposited amyloid thought to cause organ dysfunction in patients with AL amyloidosis. Preclinical research has shown that NEOD001 binds to both soluble and insoluble aggregated kappa and lambda light chains and recognizes an epitope that is exposed at the earliest stages of abnormal light chain misfolding through aggregation of deposited amyloid involved in AL amyloidosis. Birtamimab has recently been listed as the recommended international nonproprietary name (INN) for NEOD001.
About AL Amyloidosis
Systemic amyloidoses are a complex group of diseases caused by tissue deposition of misfolded proteins that result in progressive organ damage. AL amyloidosis, the most common type, is a rare, progressive, and typically fatal disease caused by extracellular deposition of misfolded immunoglobulin light chains. An excess of light chains prone to misfolding are produced by clonal plasma cells. Soluble toxic aggregates and deposited fibrils (amyloid) lead to progressive failure of vital organs including the heart, kidneys and nervous system, causing significant morbidity and mortality. It is estimated that approximately 30,000 - 45,000 patients in the U.S. and
This press release contains forward-looking statements. These statements relate to, among other things, the results from post hoc analyses that reveal a potential survival benefit of NEOD001 in the category of patients with the highest risk of early mortality (
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Source: Prothena Corporation plc