“The suggestion of a separation with a relative reduction of amyloid in the IV group [in both of the alternate assessments] was very encouraging,” Dr. Salloway said.
In a small subset of patients with complete CSF data (30 subcutaneous and 25 IV patients), crenezumab was associated with a significant increase in Abeta42, suggesting that it was interacting with amyloid brain plaques.
However, there was no movement in tau or phosphorylated tau, no changes in brain volume on MRI, and no changes in FDG-PET results.
The negative results may seem disappointing, but they don’t necessarily mean failure, Dr. Maria Carillo said in an interview.
Although disappointing in some ways, the BLAZE study did exactly what a phase II study should, said Dr. Carillo, vice president of medical and scientific relations for the Alzheimer’s Association. It provided good safety data and just enough efficacy data to strengthen the phase III API trial.
“Yes, BLAZE was a negative trial, but it informed the Colombian team,” she said. “It told them that the IV dosing was better. It told them that higher doses would be better. That’s critical, regardless of this study’s negative results.”
Alzheimer’s researcher Peter Davies, Ph.D., said in an interview, “I’m disappointed. It is hard to understand how the high dose of crenezumab does not move the amyloid imaging signal – unless of course this is just too crude a measure. The CSF data did appear promising, but the lack of effect on cognitive function is what is going to decide the fate of this treatment.” Dr. Davies is the director of the Litwin-Zucker Research Center for the Study of Alzheimer’s Disease at Hofstra North Shore-Long Island Jewish School of Medicine.
Both BLAZE and API are sponsored by Genentech. Dr. Salloway has been a consultant for Roche, Lilly, and Genentech, and disclosed a number of other financial relationships with pharmaceutical companies.
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