Merck insomnia drug put to bed

Gaboxadol was designed by Lundbeck in collaboration with Merck & Co. It aimed to relax the brain through activating a certain receptor called gamma-aminobutyric acid receptor A (GABA-A). However, in an event both have described as "disappointing", it has now failed a Phase III clinical trial due to unacceptable side effects and will be shelved. Merck & Co. originally committed up to $270m (€203m) to the project in 2004 and was so confident in the drug, it even extended the collaboration later in that year. The news has sent Lundbeck's stock plummeting around 16 per cent to $23.5. When developing a sleeping drug, the US Food and Drug Administration (FDA) requires that a company must look at possible side effects if the drug is abused. In a large clinical programme involving over 4000 patients, Anders Gersel Pedersen, head of development at Lundbeck, said the company was surprised to discover an increased number of psychiatric side effects in these patients. These strange side-effects included disorientation and hallucinations. The effects were also seen in other patients who had taken the medicine above the prescribed dose. These findings were coupled with the drug not consistently proving effective at treating insomnia and insufficient efficacy at low doses and would have led to difficulties in prescribing the drug safely. ​"We did not want to bring a product to market with such a shallow risk/benefit profile,"​ said Pedersen. "When developing new and innovative medicines there are always risks of failure, particularly for broad-based therapeutics which often carry a higher threshold for demonstrating value to physicians, and ultimately to patients."​ Asked whether gaboxadol might be used to treat any other diseases, Lundbeck CEO Claus Braestrup said: "We will consider alternatives but it is not likely we will go forward [with the drug]."​ There are many drugs to modulate GABA-A on the market, classified by chemical structure. Benzodiazepines include diazepam (perhaps best known under the trade name Valium) and , although effective at initiating sleep, they have several side effects. These include the risk of developing tolerance to the drug and the potential for a 'hangover effect' - a sensation of dullness and lethargy upon awakening. Several non-benzodiazepines are on the market or in development. However, gaboxadol differed from other drugs that modulate GABA-A activity as it acted directly on the receptor, according to Lundbeck - specifically a receptor subtype only found outside of synapses. The company hoped the different mechanism of action would improve so called slow wave sleep and therefore improve patient functioning the next day. It is not the first time insomnia drugs that interact with the GABA-A receptor have suffered problems. Last June, Pfizer announced it was giving up on drug candidate indiplon. They subsequently gave the drug rights back to Neurocrine Biosciences - which plans to resubmit the drug for approval in the US by the end of June this year. Evotec is also developing a GABA-A modulating insomnia drug, which is currently in Phase II clinical trials. EVT-201 is different to other drugs in that it is only a partial receptor agonist and works by binding to a different part of the receptor, changing its structure and activity.