Bapi programme shelved as second Alzheimer’s trial fails

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Whatever remaining hope there was that bapineuzumab would succeed in a second Alzheimer’s disease subgroup were put to rest today. Pfizer and Johnson & Johnson have discontinued all remaining phase III work on the antibody after it did not help improve cognition and functional performance in non-carriers of the ApoE4 gene.

The biggest blow was struck to partner Elan, which saw its New York listed shares plummet another 6% to $10.54 today; those shares have sunk by more than one-fifth since news that a first trial, in ApoE4 carriers, failed last month. Reflecting signs that research on Alzheimer’s treatments is shifting to earlier-stage patients, the partners are continuing phase II work with a subcutaneous formulation.

Decisive

It was pretty clear that bapi would fail when the results from the first trial, in ApoE4 carriers, failed (Phase III bapi failure opens up Russian roulette opportunity, July 24, 2012). In those patients, whose ApoE4 status increases their risk of developing Alzheimer’s disease, earlier-stage trials had not shown much promise. Most of the hope for the antibody had rested in the non-ApoE4 population.

However once again the intravenous formulation of the drug proved no better than placebo in maintaining cognition and function, and with some surprising swiftness and decisiveness the partners pulled the plug on the amyloid-fighting product. Two ongoing trials, in non-North American populations run solely by Pfizer, will also be wound up; Pfizer told analysts there were no signs of efficacy even within subgroups of the non-ApoE4 population, suggesting absolutely no commercial future for the drug.

In addition to Elan’s losses, Pfizer’s shares sunk 2% to $23.79 in early trading today and Johnson & Johnson’s were off by less than 1% to $68.61. Pfizer was developing the antibody in conjunction with Janssen Alzheimer Immunotherapy, a joint venture between J&J and Elan in which the Irish partner held a 49.9% stake.

Hit in the crossfire was Eli Lilly, whose shares fell 2% to $42.75 as bapi’s failure reflects badly on the Indiana group’s own amyloid-combating antibody, solanezumab. Lilly is expecting to report data from that compound sometime before the end of September. Given that few companies face the challenges to a patent estate nor have gambled on R&D the way Lilly has, even with the expectation of failure a poor outcome for solanezumab would do little to reinforce the strategic decisions of its executive team.

Early stage

The sole glimmer of hope – and it is a small one at that – is the continuation of phase II work on the subcutaneous formulation of bapi. Right now that formulation is being tested in 80 patients with mild to moderate disease to detect positive biomarker data, results are not expected until next year.

With recent failures in Alzheimer’s, one theory is that amyloid-targeting agents need to be used in earlier-stage patients, before symptoms become apparent – research on Roche’s crenezumab being an example (Alzheimer’s research moves earlier as amyloid data approaches, May 16, 2012). Analysts from Bernstein wrote that subcutaneous bapi could be another candidate for earlier stage patients.

But for now, Alzheimer’s disease research has suffered another disappointment, and whilst expected, it is no less devastating for the field – research on earlier stage patients is really just beginning in earnest now. A surprise for solanezumab would help raise spirits, but almost nobody is betting on that outcome.

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com

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