Therapy Type: Immunotherapy (active) (timeline)
Target Type: APP and Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease,
U.S. FDA Status: Alzheimer's Disease (Phase 2), (Phase 2)
Company: Novartis Pharmaceuticals Corporation
Approved for: None
This is an active vaccination strategy that aims to elicit a strong antibody response while avoiding inflammatory T cell activation (reviewed in Lemere and Masliah, 2010). CAD106 combines multiple copies of Aβ1-6 peptide derived from the N-terminal B cell epitope of Aβ, coupled to a Qβ virus-like particle. In animals, CAD106 induced Aβ-antibody titers without activating Aβ-reactive T cells. Administration of CAD106 to APP-transgenic mice showed a reduction of amyloid accumulation in the brain (Wiessner et al., 2011).
In 2008, a one-year Phase 1 trial of two doses of CAD106 in 58 people with mild to moderate Alzheimer's disease in Sweden concluded that the vaccine dose-dependently induced Aβ IgG titers that met prespecified "responder" criteria for an immune response while being generally safe and well-tolerated. No meningoencephalitis was reported (Winblad et al., 2012). CAD106 has since been tested with subcutaneous and intramuscular injections in five subsequent multicenter Phase 2 trials in the United States and Europe. Two 66-week extension trials ending in 2010 and 2011 explored antibody response and tolerability of additional doses, i.e., different longer-injection/booster-shot regimens. They found prolonged antibody titers in responders. A 90-week trial of 177 people with mild to moderate Alzheimer's tested two doses of vaccine and two doses of adjuvant at 36 study sites. This trial contains pharmacogenomic and amyloid PET substudies. This trial has concluded. Partial results have been reported at conferences to indicate antibody maturation and continued safety after seven injections and follow-up of two and a half years. To view all clinical trials, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 2
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
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- Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy?. Nat Rev Neurol. 2010 Feb;6(2):108-19. PubMed.
- Madrid: News from the Vaccine Front—Phase 1 Hopefuls
- Slow and Steady—Active Immunization Crawls Toward Promise
- Kingwell K. Alzheimer disease: Amyloid-β immunotherapy CAD106 passes first safety test in patients with Alzheimer disease. Nat Rev Neurol. 2012 Aug;8(8):414. PubMed.