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Name: Crenezumab
Synonyms: MABT5102A , RG7412
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Genentech
Approved for: None


Crenezumab is a passive immunotherapy approach in which patients are treated with monoclonal antibodies that specifically recognize Aβ peptides. Crenezumab recognizes multiple forms of aggregated Aβ, including oligomeric and fibrillar species and amyloid plaques with high affinity, and monomeric Aβ with low affinity. This humanized antibody uses an IgG4 backbone. It was engineered to clear excess Aβ while exerting reduced subsequent effector function on microglia; the rationale is to stimulate amyloid phagocytosis while limiting release of inflammatory cytokines as a way to avoid side effects such as vasogenic edema (see Adolfsson et al., 2012).


Two Phase 1 safety trials in healthy volunteers and people with Alzheimer's disease produced no evidence of vasogenic edema or cerebral microhemorrhage, allowing Phase 2 to use higher doses and achieve higher brain exposure than was possible with previous immunotherapy approaches. ABBY was a Phase 2 trial evaluating up to 15 mg/kg per month of subcutaneous crenezumab injections, conducted at more than 90 sites in North America and Europe in 450 people with mild to moderate AD. ABBY and a 91-patient biomarker study called BLAZE were completed in spring 2014; both continued into an open-label extension trial of 361 patients that will run until May 2016. ABBY missed its primary endpoints of change on ADAS-cog and CDR-SOB. Further analysis suggested a possible efficacy signal in mild AD, similarly to solanezumab's EXPEDITION 1 and 2 results (Jul 2014 conference news). The BLAZE study reported no separation between treatment and placebo groups on the primary endpoint of PET amyloid imaging, but did report a separation on the secondary endpoint of CSF Aβ (see Dec 2014 conference news). 

Crenezumab is also being tested in a prevention paradigm. In a landmark, adaptive, five-year study that started in 2013, crenezumab is the first immunotherapy to be evaluated as part of the Alzheimer Prevention Initiative (see May 2012 conference news). Bimonthly, subcutaneous injection of crenezumab is being compared to placebo for its ability to stave off cognitive decline and affect Alzheimer's biomarkers in presymptomatic carriers of autosomal-dominant presenilin mutations, such as PSEN1 E280A. Most trial participants live in and near Medellin, Colombia; some U.S. participants with similarly predisposing gene mutations also will be recruited. The participants in this trial did not meet criteria for mild cognitive impairment at the time of enrollment. The trial uses a composite consisting of five separate cognitive tests as its primary outcome (see Feb 2013 Webinar). It also uses an extensive list of secondary outcomes, including safety, time to progression to MCI, as well as clinical outcomes and fluid and imaging biomarkers. This Phase 2 trial expects to recruit 300 participants and is set to run until 2020. 

In February 2015, Genentech started another 72-patient Phase 1 study to evaluate two doses of intravenous crenezumab; doses or treatment duration were not disclosed but a follow-up study will run up to 21 months. In July 2015, it was announced that crenezumab would move into Phase 3, initially with a study in prodromal AD (see company press release).

This antibody is listed in under both crenezumab and MABT510A.



Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025
Genentech NCT01343966
Genentech NCT01397578
Genentech NCT01723826
Genentech NCT01998841


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News Citations

  1. Crenezumab Disappoints in Phase 2, Researchers Remain Hopeful
  2. Immunotherapy I: Baby Steps, but No Breakthroughs
  3. NIH Director Announces $100M Prevention Trial of Genentech Antibody

Mutations Citations

  1. PSEN1 E280A (Paisa)

Webinar Citations

  1. New Frontier: Developing Outcome Measures for Pre-dementia Trials

Paper Citations

  1. . An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ. J Neurosci. 2012 Jul 11;32(28):9677-89. PubMed.

External Citations

  1. see company press release
  2. crenezumab
  3. MABT510A

Further Reading


  1. . Comparing the efficacy and neuroinflammatory potential of three anti-abeta antibodies. Acta Neuropathol. 2015 Nov;130(5):699-711. Epub 2015 Oct 3 PubMed.