Event – Transition to agitation the solution for Elan cast-off

Analysis

Having like most new projects failed to slow the progression of Alzheimer’s disease, ELND005 is getting a second chance next month when Transition Therapeutics reports data on whether the beta-amyloid inhibitor can prevent neuropsychiatric complications.

The hope for the phase II trial is that the pill can show a decrease in agitation or aggression in Alzheimer’s patients, based on the post-hoc findings of a study that missed on cognition. Analysts have taken heart in Transition’s recent decision to cut the size of the agitation trial by a fifth, reasoning that executives must be confident that they will have a statistically valid result with a smaller population.

On the other hand, reducing the study might have been the result of financial constraints, introducing the added risk that the trial might end up being underpowered. 

Calming

Transition hopes that ELND005, or scyllo-inositol, will be able to improve patients’ scores in the neuropsychiatric inventory agitation/aggression domain, a measurement of how behavioural changes in Alzheimer’s disease affect caregivers. In the earlier phase II trial that failed to show an effect on cognition, the pill reduced the emergence of new neuropsychiatric symptoms.

While this would not be the answer that a truly disease modifying Alzheimer’s drug would provide, an agent that could prevent neuropsychiatric complications would be welcome; agitation and aggression increase the burden on paid and informal caregivers, and are associated with additional health problems.

Scyllo-inositol is another attempt to limit the damage of Alzheimer’s by disrupting the accumulation of amyloid plaques in the nervous system. The small molecule is able to cross the blood-brain barrier and is believed to have two beneficial effects: reducing levels of myo-inositol similarly to other neuropsychiatric drugs, and reducing levels of circulating beta amyloid fibrils before they can accumulate and interfere with neuronal transmission.

Beta amyloid, of course, has been the target of numerous projects, all of which have failed to alter the course of the disease, but despite this it remains the main hypothesis for developers (Lilly’s sola still has a mountain to climb, June 11, 2015).

Transition has been clever in pursuing a subset of patients, which would entail showing improvements on more narrowly defined criteria and likely require fewer patients in its clinical programme to gain approval – Lilly has enrolled nearly 7,000 patients in trials of solanezumab.

Budgeting

A small programme is probably all Transition can manage for ELND005 for now in any case, regardless of what earlier trials found in Alzheimer’s progression. The agent was at one point partnered with now defunct Elan – which had a solanezumab rival in bapineuzumab – but with that company’s acquisition by Perrigo the commercial rights and development costs rest with Transition.

Transition will also owe royalties to Perrigo if ELND005 succeeds. Net of these payments, analysts from HC Wainright forecast revenue at $474m in 2020.

The company had C$50.2m ($40.9m) of cash in the bank at March 31 after a US$23m fund raising in February. Having spent C$36.8m on R&D for two phase II assets in the nine months ended March 31 it needs to keep its ambitions modest.

A successful result in the Alzheimer’s agitation trial could stoke partnering interest. With Transition having also working on two Lilly-partnered diabetes projects it would do well to limit the cash it is now devoting to ELND005.

Trial ID NCT01735630

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com or follow @ByJonGardner on Twitter

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