Image from Ed Uthman
Micrograph showing amyloidosis
Prothena Corporation plc is discontinuing development of NEOD001, an investigational antibody intended for the treatment of AL amyloidosis.
The company’s decision was based on results from the phase 2b PRONTO study and a futility analysis of the phase 3 VITAL study.
NEOD001 did not meet the primary or secondary endpoints of the PRONTO study, so Prothena asked an independent data monitoring committee to review a futility analysis of the ongoing VITAL study.
The committee recommended discontinuation of the VITAL study, so Prothena decided to discontinue all development of NEOD001, including the VITAL study and open-label extension studies.
“We are deeply disappointed by this outcome, particularly for patients suffering from this devastating disease,” said Gene Kinney, PhD, president and chief executive officer of Prothena.
“We are surprised by the results from these 2 placebo-controlled studies and will continue to analyze the resulting data to share insights with our collaborators in the scientific, medical, and advocacy communities.”
Phase 3 VITAL study
The VITAL study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in treatment-naïve patients with AL amyloidosis and cardiac dysfunction.
The study enrolled 260 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 or placebo via intravenous infusion every 28 days. Patients in both arms received concurrent standard of care therapy.
The composite primary endpoint was event-based, with all-cause mortality or cardiac hospitalizations counted as events.
The futility analysis, based on 103 adjudicated events of the 156 events specified to complete the study, was not statistically significant. The hazard ratio was 0.84 favoring NEOD001 versus the control arm.
Phase 2b PRONTO study
The PRONTO study was a multicenter, randomized, double-blind, placebo-controlled study of NEOD001 in previously treated patients with AL amyloidosis and persistent cardiac dysfunction.
The study enrolled 129 patients who were randomized on a 1:1 basis to receive 24 mg/kg of NEOD001 (n=66) or placebo (n=63) via intravenous infusion every 28 days.
There was no significant difference between the treatment arms for any of the study’s endpoints.
The primary endpoint was cardiac best response, as assessed by N-terminal pro B-type natriuretic peptide (NT-proBNP) through 12 months of treatment. This endpoint was achieved by 39.4% of patients in the NEOD001 arm and 47.6% in the placebo arm.
The NT-proBNP rate of change (slope) through 12 months of treatment was 9.80 in the NEOD001 arm and 81.42 in the placebo arm.
The mean change in Short-form 36 Physical Component Summary Score after 12 months of treatment was 0.19 and 0.97, respectively.
The median change in 6-Minute Walk Test distance after 12 months of treatment was 19.25 m and 8.00 m, respectively.
And the mean change in Neuropathy Impairment Score of the Lower Limb after 12 months of treatment was -1.20 and -0.60, respectively.
The rate of renal best response (as assessed by proteinuria and estimated glomerular filtration rate) through 12 months of treatment was 53.8% in the NEOD001 arm and 33.3% in the placebo arm.
The rate of all-cause mortality was 4.5% (n=3) and 9.5% (n=6), respectively.
Prothena said NEOD001 was generally safe and well tolerated in this trial.