Event – Amyloid-Targeting Alzheimer's Therapies Seek Crumbs of Comfort

June 26, 2012 Event – Amyloid-targeting Alzheimer’s therapies seek crumbs of comfort

Jacob Plieth

With the winding down of pivotal studies of Elan’s bapineuzumab and Lilly’s solanezumab – novel, disease- modifying monoclonal antibody approaches for Alzheimer’s – this notoriously difficult therapy area is hotting up, although few analysts expect a knockout result when topline data are made public in the coming weeks.

Nevertheless, a lot is at stake, not least because of the huge potential value of the Alzheimer’s market and Elan and Lilly’s keenness to shake off previous failures. As hopes of success are low investors might be pricing in much of the failure risk, meaning that any positive signals that can be salvaged from the data could have a disproportionately positive effect on the developers’ share prices.

Company Elan Eli Lilly

Product bapineuzumab solanezumab

Market cap $8.3bn $48.1bn

Product NPV $4.2bn $1.0bn

% of market cap 51% 2%

Event type Phase III results

Date Q3 2012

Great scepticism

After lacklustre earlier studies a great deal of scepticism surrounds bapineuzumab and solanezumab - the first amyloid-targeting approaches that offer disease-modifying potential in Alzheimer’s. However, the huge prize at stake and the fact study failures might be due to the poorly understood nature of the disease rather, than a lack of efficacy, have ensured their continued development.

Both projects work by binding to amyloid proteins to promote their clearance from the brain; the formation of amyloid plaques – rather than the protein’s breakdown and elimination, as seen in healthy individuals – is one factor contributing to the degeneration of Alzheimer’s disease patients’ brain cells.

However unlikely a near-term bapineuzumab launch is, consensus estimates are for it to post sales of $701m by 2018. Applying a 75% probability – a bullish scenario – the drug’s NPV according to EvaluatePharma’s NPV Analyzer is $5.5bn, of which Elan accounts for the lion’s share. The drug is worth $4.2bn to Elan, or almost half its market cap, meaning it has the most to gain if bapineuzumab does come good. As it accounts for less that 1% of the share price of development partners Pfizer and Johnson & Johnson any effect will be more modest.

The project has in previous trials failed to show the disease-modifying effect that had been expected, but there is some hope that it will prove positive in non-carriers of the ApoE4 gene, which make up around half of all Alzheimer’s patients. Two studies – one in ApoE4 carriers and the other in non-carrier patients – complete this year, in April and August respectively.

For Elan, whose shares are up 30% year on year, rumours of a takeover could again start to circulate given that its CEO, Kelly Martin, plans to leave after the bapineuzumab studies read out (Elan chief sits tight to steer bapineuzumab through pivotal data readout, March 1, 2012).

If expectations for bapineuzumab’s success are low, those for solanezumab are even more remote: the drug’s NPV stands at $1.0bn, with 2018 consensus sales of a mere $436m. Its proportional importance to Lilly, whose market cap stands at $48bn, is therefore much smaller, although it is the most advanced R&D hope of a company with one of the toughest patent expiry cliffs in the industry. Solanezumab is being studied in two clinical trials, codenamed Expedition and Expedition2, in a mixture of ApoE4 carriers and non-carriers; pre-specified analyses will allow treatment effects to be assessed in the two groups separately, although mechanistic subtleties mean solanezumab is thought less likely to work in the non-ApoE4 subgroup than bapineuzumab. The studies survived a futility analysis early this year.

Topline data in August?

With a six to eight-week timeframe to get data after trial completion, topline results from Expedition and the study of bapineuzumab in ApoE4 carriers could be announced in August. Analysts expect full results at the Clinical Trials on Alzheimer’s Disease conference at the end of October.

Ultimately, the most realistic outcome for both projects might be that they show benefits in patient subsets even if primary endpoints are missed; for instance, milder patients with less disease progression could be the most promising population.

Even this could be more than either the failure-prone Lilly or the soon-to-be rudderless Elan dare to hope for.

Drug Study Trial ID Status

solanezumab Expedition NCT00905372 completed April

bapineuzumab ApoE4 carriers NCT00575055 completed April

solanezumab Expedition2 NCT00904683 ending June

bapineuzumab ApoE4 non-carriers NCT00574132 ending August