Date: 2016-12-09
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 9th Clinical Trials on Alzheimer's disease Conference (CTAD) in San Diego
Company: Genentech, a member of Roche Group (USA - CA - Switzerland)
Product: anti-Abeta antibody MABT5102A (crenezumab)
Action
mechanism: monoclonal antibody. MABT5102A (crenezumab) is a fully humanized IgG4 monoclonal antibody to Abeta that binds both monomeric and oligomeric forms of Abeta, inhibits Abeta aggregation, and promotes Abeta disaggregation. MABT5102A was discovered and humanized by AC Immune through its proprietary SupraAntigen technology. The drug candidate was discovered by AC Immune. In 2006 AC Immune closed an exclusive out-licensing agreement for its anti-Abeta program with Genentech, under which Genentech develops the anti-Abeta antibody for the treatment of Alzheimer´s Disease. Genentech has full ownership and global responsibility for clinical development, manufacturing and commercialization of the antibody, including all regulatory activities. In return, AC Immune received an upfront payment, a milestone payment when the first patient was dosed under the Phase I clinical trial, and now another payment upon the start of Phase II. In addition AC Immune obtained funding through a research collaboration that was successfully concluded after three years in 2009. The contract provides potential revenues of over $ 300 million for AC Immune through payments upon successful completion of clinical and regulatory milestones in Alzheimer´s disease and additional applications. Additionally, upon commercialization of a product AC Immune will receive royalties.
Disease: Alzheimer disease
Therapeutic area: Neurodegenerative diseases
Country: USA
Trial
details: This randomized, placebo-controlled, double-blind, parallel-arm study will evaluate the safety and tolerability of at least two dose levels of intravenous (IV) crenezumab in 24-72 participants with mild to moderate Alzheimer disease (AD) (mini-mental state examination [MMSE] 18 to 28 points, inclusive). An optional open-label extension (OLE) will be offered after the completion of initial double-blind stage. (NCT02353598)
Latest
news: * On December 9, 2016, AC Immune announced that its partner Genentech, member of Roche group, has presented important data to support the unique binding and increased dosing of its Alzheimer's therapy on crenezumab, an anti-Abeta antibody. These data were presented at the 9th Clinical Trials on Alzheimer's disease Conference (CTAD) in San Diego, USA: they were from a Phase 1b safety study and an exposure-response model to evaluate the best dose of crenezumab for the treatment of people with Alzheimer's disease. The model predicts, relative to the Phase 2 trials, an improved outcome of the CREAD Phase 3 clinical trial in patients with prodromal-to-mild Alzheimer by using the higher dose of 60mg/kg of crenezumab.
Genentech presented the results of the first two cohorts of the Phase 1b crenezumab dose escalation study in 52 patients with mild-to-moderate Alzheimer's disease. No dose-limiting toxicities were observed at 30, 45 and 60mg/kg doses of crenezumab. No events of Amyloid Related Imaging Abnormality-Edema (ARIA-E) were observed in the Phase 1b study and only a few patients (6 of 52) showed asymptomatic Amyloid Related Imaging Abnormality-Hemsiderin(ARIA-H) which did not result in treatment discontinuation. The pharmacokinetic profile of crenezumab is dose proportional up to the 60mg/kg dose and is consistent with historical data. The serum concentrations at this dose are four fold higher than in the 15mg/kg IV every four weeks dose used in the Phase 2 trials. These safety and pharmacokinetic data of the Phase 1b dose escalation study support the continued treatment of patients with crenezumab at a higher dose of 60mg/kg.
Genentech is currently evaluating the clinical efficacy and safety of crenezumab in a Phase 3 clinical trial, CREAD, in 750 participants with prodromal or mild Alzheimer's disease, which started in Q1 2016 and is expected to read out in 2020. In addition crenezumab was chosen by an international panel of experts, including the US National Institutes of Health, for use in a first-ever prevention trial in Alzheimer's disease in a large extended family in Colombia (API ADAD) in 2012.
