LONDON ¿ Cerebrus plc, which focuses on central nervous systems diseases, has agreed to license sabcomeline from SmithKline Beecham plc (SKB) after the pharmaceutical company decided not to proceed with the compound following a Phase III trial for the treatment of memory loss in Alzheimer¿s disease.
Cerebrus plans to develop the compound, a muscarinic agonist, for the treatment of behavioral problems, a major problem in advanced Alzheimer¿s, for which the only current treatment is antipsychotic drugs.
John Hutchison, development director of Cerebrus, of Wokingham, Berkshire, told BioWorld International that sabcomeline reached Phase III in the U.S. and Europe as Memric, but did not meet the primary endpoints in terms of improvements in cognition. ¿There was some effect on memory enhancement but it was not sufficiently large enough for the compound to compete against acetylcholinesterases.
¿However, further analyses of the data showed improvements in behavioral symptoms of dementia, particularly in a subgroup of patients with pronounced behavioral disturbance.¿
Under the terms of the agreement, Cerebrus issued 8 million convertible preference shares at #1 each to SKB, of London, and will make milestone payments. SKB has an option to commercialize the compound on completion of Phase III, but if it does not take up the right Cerebrus is free to market it alone or with a partner. The commercializing partner would pay milestones and royalties on sales.
Hutchison said Cerebrus will start Phase IIb trials later this year. ¿The size of the trial, at 300 patients, will be based on reasonably accurate statistical data from the SKB trial.¿
To date sabcomeline has been taken by 2,000 Alzheimer¿s patients. The trial will run for 18 months and be followed by a Phase III lasting two years. Cerebrus expects to spend #4 million to #5 million on the compound.
The behavioral problems associated with Alzheimer¿s disease usually start after a patient¿s memory fails. ¿Most of the patients in the trial will have frank behavioral disturbance, including aggression, delusions, agitation, wandering and hallucinations,¿ Hutchison said.
It is the presence of such disruptive behavior that usually triggers the move to institutional care. Antipsychotic drugs are the most widely used treatment, but apart from being off-label, they have significant side effects, including sedation and cardiovascular effects.
Adding a Phase III compound to the portfolio is a significant advance for Cerebrus, which has particular skills in early stage development of CNS treatments based on sophisticated animal models of human disease. Hutchison said the company has employees who have previously worked on similar compounds.
¿We see this as an important move in the development of the portfolio to add later-stage projects,¿ he said. Cerebrus is shaping up for a flotation but, with the current state of the markets, is not putting any time frame on when that will take place.