Vasogenic Brain Edema Plagues Bapineuzumab Development
The clinical development of bapineuzumab in Alzheimer's disease has hit another snag. Codevelopers Elan and Wyeth announced today that the highest dosage of the anti-beta amyloid mAb, 2.0 mg/kg, will be discontinued in 2 ongoing phase 3 trials (NCT00667810 and NCT00574132), owing to the associated risk of vasogenic brain edema detected on MR images. The decision was made in conjunction with a review of unblinded data from the phase 3 trials by an independent Safety Monitoring Committee.
The affected trials are assessing bapineuzumab in patients with mild-moderate AD who do not carry the risk factor of the apolipoprotein E4 allele (40%-70% of AD patients). Phase 2 data from last year indicated that the agent was no better than placebo in 240 AD subjects. However, a post-hoc analysis indicated that bapineuzumab provided "statistically significant and clinically meaningful benefits" in non-ApoE4 carriers. These data also indicated that ApoE4 carriers may be especially prone to drug-associated vasogenic edema.
Current phase 3 study arms assessing 0.5- or 1.0-mg/kg dosages of bapineuzumab in noncarrier patients will continue. Patients originally assigned to the highest dosage will be allowed to continue the trial with 1.0-mg/kg treatment. Protocols for phase 3 trials of the mAb in ApoE4 carriers (NCT00676143 and NCT00575055)—which are assessing only 1 bapineuzumab dosage*—remain unchanged.
mAb = monoclonal antibody.
* 0.5 mg/kg according to MedPage Today.