Name:	CAD106
Therapeutic Applications:	Mild Alzheimer Disease
Therapy Types:	Protein: active immunization, peptide vaccine
Mechanisms:	Aβ(1-6) immunotherapy
Development Status:	investigational in U.S.
FDA Phase:	Phase II/IIa/IIb
Role in Alzheimer's Disease:	CAD106 is a vaccine that presents multiple copies of Aß1-6 peptide derived from the N-terminal B cell epitope of Aß while avoiding T cell activation (reviewed in Lemere and Masliah 2010) coupled to the Qß virus-like particle. In animals, CAD106 induced Aß-antibody titers without activating Aß-reactive T-cells. Administration of CAD106 to APP transgenic mice showed a reduction of amyloid accumulation in the brain. Data from a first-in-man a 52-week, two-center, randomized, double-blind, placebo-controlled, parallel group clinical trial in Sweden, based on 58 mild to moderate AD patients assessed antibody titers from two doses tested (50 μg at 0/6/18 weeks and 150 μg at 0/2/6 weeks). CAD106 induced a measurable specific antibody response against Aß with a 2-fold increase observed in the high dose group. Exploratory outcome measures CSF Aβ levels and whole brain volume MRI did not show differences between treated vs placebo patients. (See Winblad et al 2009).
Side Effects:	In the Swedish trial no cases of meningoencephalitis were detected clinically. Adverse events were predominantly mild and injection-related. Serious adverse events were reported in Cohort I for 4/24 (17%) patients on CAD106 and 1/7 (14%) on placebo, and in Cohort II for 4/22 (18%) patients on CAD106 and none on placebo. (See Winblad et al 2009).
Companies:	Novartis Pharmaceuticals Corporation
Notes:	Four Phase II clinical trials testing CAD106 in AD are ongoing; two open label extension trials inviting previous participants of completed CAD106 trials ( NCT01023685 and NCT00956410), one is ongoing and no longer recruiting participants ( NCT00795418). A fourth Phase II study to assess safety, tolerability and antibody response in mild AD ( NCT01097096) is currently recruiting participants, and will be located in multiple sites in the US, Canada, and EU. This entry was last updated October 1, 2010.

References

Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol. 2010 Feb;6(2):108-19. Review. Erratum in: Nat Rev Neurol. 2010 Apr;6(4):183. Nat Rev Neurol. 2010 Jun;6(6):296. Abstract

Winblad BG, Minthon L, Floesser A, Imbert G, Dumortier T, He Y, Maguire P, Karlsson M, Ostlund H, Lundmark J, Orgogozo JM, Graf A, Andreasen N. RESULTS OF THE FIRST-IN-MAN STUDY WITH THE ACTIVE Ab IMMUNOTHERAPY CAD106 IN ALZHEIMER PATIENTS. Alzheimers Dementia 2009;5:P113–P114 O2-05-05. Abstract