Lundbeck and Otsuka are putting their faith in Alzheimer’s disease drug candidate Lu AE58054 and starting the first of four planned phase III trials of the drug.
The path towards an effective new Alzheimer’s treatment is littered with failed candidates, but Lundbeck and Otsuka are pinning their hopes on compound with a markedly different mechanism from most other companies working on the disease.
Lu AE58054 is a serotonin (5-HT) 6 receptor antagonists that has already produced promising results in phase II studies, and Lundbeck and Otsuka are confident enough in the data to start a 3,000-patient phase III programme of the drug.
Serotonin is known to be reduced in patients with Alzheimer’s, particularly in areas of the brain associated with cognition, such as the cortex and the hippocampus. It is thought that blocking 5-HT6 receptors can improve cognition and memory by inhibiting the activity of other neurotransmitters that dampen down brain activity.
Lundbeck and Otsuka have opted to test Lu AE58054 on top of treatment with the established Alzheimer’s therapy donepezil, which acts by booting levels of the neurotransmitter acetylcholine in the brain.
The first 930-patient phase III study will look at a range of doses of the drug candidate alongside donepezil in patients with established, mild-to-moderate Alzheimer’s and will take three years to complete.
Any Alzheimer’s treatment can only be regarded as speculative in light of the high number of candidate failures, but as Lu AE58054 acts on synaptic neurotransmission – rather than a hypothetical underlying disease mechanism – it arguably stands a better chance of reaching the market than drugs targeting amyloid or tau protein, for example.
Working via neurotransmitters may however also put a cap on the benefit of the treatment. Current drugs that boost levels of acetylcholine and glutamate show limited benefits because they are unable to restore neural circuits lost to the Alzheimer’s disease process.
Regardless, it has been 10 years since the last new Alzheimer’s treatment reached the market – Lundbeck’s glutamate (NMDA) antagonist Ebixa (memantine), which is sold as Namenda by Forest Labs in the US – and even a modest boost to the efficacy of current therapy would be a big step forward.
Analysts at Jyske Bank said earlier this month that positive results in phase III would be a “huge upside” to Lundbeck as the drug currently does not really feature in future sales forecasts.
Lundbeck’s R&D chief Anders Gersel Pedersen said: “Following consultations with different health agencies, with Otsuka we are now ready to start this major programme.”
“We believe there is a strong need for more treatment options for patients with Alzheimer’s, and we see Lu AE58054 as a potentially promising therapy for this devastating disease.”
Lundbeck and Otsuka are thought to be a little out in front in the bid to bring a 5-HT6 antagonist to market for Alzheimer’s, but GlaxoSmithKline is not far behind with SB742457, as is Pfizer with its PF-5212377 (both in phase II).
Meanwhile, the start of the pivotal trials programme is another fillip for Lundbeck, which passed a major milestone last month when it won US approval for its new antidepressant Brintellix (vortioxetine).
The drug is a successor to its big-selling Cipralex/Lexapro (escitalopram) product that lost patent protection in the US last year.