Therapeutics

Octagam®10%

Overview

Name: Octagam®10%
Synonyms: Intravenous Immunoglobulin, NewGam
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Amyloid-Related (timeline), Inflammation (timeline)
Condition(s): Alzheimer's Disease, Mild Cognitive Impairment
U.S. FDA Status: Alzheimer's Disease (Inactive), Mild Cognitive Impairment (Inactive)
Company: Octapharma
Approved for: Immunodeficiency disorders

Background

NewGam/Octagam® is an intravenous immunoglobulin preparation by the Switzerland-based company Octapharma. It is a marketed product. The rationale of evaluating it in Alzheimer's disease, as for other intravenous immunoglobulin preparations such as Gammagard® and Flebogamma (as Gamunex), is that naturally occurring polyclonal autoantibodies against Aβ may be protective and are reduced in Alzheimer's disease (see Weksler et al., 2002).

Findings

The first trial of this IVIG preparation in Alzheimer's evaluated six different doses of Octagam 10 percent against two placebo comparators in a six-month trial of 58 people with mild to moderate AD. This multicenter Phase 2 trial has been completed. This trial missed its primary endpoint of change in plasma Aβ levels, and was negative for most of its secondary biomarker outcomes with the exception of a signal suggesting a benefit for cerebral metabolism. None of the doses tested showed any benefit for cognition or function (see Dodel et al, 2013; Feb 2013 news).

A second, single-center Phase 2 study conducted at Sutter Institute for Medical Research in Sacramento, California, investigated the long-term effects of a short course of this IVIG preparation. Octagam 10 percent (0.4 g/kg) or saline placebo was infused every other week for two months in 50 people with amnestic MCI due to AD, with two years of follow-up. Initial results on 28 patients assessed one year after treatment indicated possible effects on the Clinical Dementia Rating Sum of Boxes and brain atrophy as seen on MRI (see Mar 2013 conference story). Full publication of the data reported less brain atrophy and a treatment benefit on ADAS-cog13 and MMSE in the IVIG group compared to the placebo group at 12 months; these differences disappeared by 24 months. The paper also reported a trend toward fewer progressions to AD dementia in the treated group at 12 months, and argued for additional research on this approach (Kile et al., 2015). In additional follow up of 27 participants, treatment did not change brain volume, cognition, or conversion to dementia at five years (Kile et al., 2021).

A single center, proof of mechanism study in five people with MCI due to AD measured brain amyloid by florbetapir PET and retinal amyloid by autofluorescent imaging. All received five infusions of 0.4 g/kg Octagam 10 percent over two months. In three of the five participants, brain amyloid was reduced one month after the last infusion; all five had lowering of amyloid in at least one eye (Kile et al., 2020).

A metanalysis of five clinical trials of intravenous immunoglobulin formulations found no evidence for improved cognition or disease modification in people with Alzheimer’s disease or MCI (Liu and Wang, 2019).

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031
Octapharma NCT00812565
N=58RESULTS
Sutter Health NCT01300728
N=50RESULTS

Last Updated: 17 Sep 2021

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References

News Citations

  1. Research Brief: Octapharma IVIg Iffy in Phase 2 Trial
  2. Quick-and-Early IVIG Therapy: Hints of Promise?

Therapeutics Citations

  1. Gammagard®
  2. Gamunex

Paper Citations

  1. . Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial. Lancet Neurol. 2013 Mar;12(3):233-43. Epub 2013 Jan 31 PubMed.
  2. . IVIG treatment of mild cognitive impairment due to Alzheimer's disease: a randomised double-blinded exploratory study of the effect on brain atrophy, cognition and conversion to dementia. J Neurol Neurosurg Psychiatry. 2015 Sep 29; PubMed.
  3. . Five-year outcomes after IVIG for mild cognitive impairment due to alzheimer disease. BMC Neurosci. 2021 Aug 6;22(1):49. PubMed.
  4. . Reduction of Amyloid in the Brain and Retina After Treatment With IVIG for Mild Cognitive Impairment. Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317519899800. PubMed.
  5. . Intravenous immunoglobulins for Alzheimer's disease and mild cognitive impairment due to Alzheimer's disease: A systematic review with meta-analysis. Expert Rev Neurother. 2019 Jun;19(6):475-480. Epub 2019 May 23 PubMed.
  6. . Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp Gerontol. 2002 Jul;37(7):943-8. PubMed.

Further Reading

No Available Further Reading