Merck Ready to Submit Belsomra to FDA for Alzheimer's Insomnia

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Merck & Company’s Belsomra (suvorexant) was approved to treat insomnia in August 2014. The company announced today that it had positive results in a Phase III clinical trial evaluating the drug for insomnia in patients with mild-to-moderate Alzheimer’s disease dementia. Merck presented the data at the American Academy of Neurology (AAN) Annual Meeting this week.

The trial looked at the efficacy and safety of Belsomra 10 mg, which could be increased to 20 mg based on patient’s response, compared to placebo in patients with mild-to-moderate Alzheimer’s dementia who also had insomnia. Mild-to-moderate Alzheimer’s was evaluated on the Mini Mental State Examination and was defined as a score of 12-26. Insomnia was defined as a mean total sleep time of fewer than 6 hours. Sleep was measured using overnight polysomnography in a sleep laboratory. Of the patients treated with Belsomra, 77% increased their dose from 10 mg to 20 mg after the second week of the trial.

The trial met both primary and secondary efficacy endpoints. Belsomra improved mean total sleep time (TST) by 28.2 minutes compared to placebo at 4 weeks, which was the primary endpoint. This compared to a mean increase from baseline of 73.4 minutes with Belsomra and 45.2 minutes with placebo.

Adverse events were reported in 22.5% of patients receiving Belsomra compared to 16.1% receiving a placebo. One patient in each group halted treatment because of an adverse event. The most common recorded adverse event was drowsiness, which was recorded as mild-to-moderate severity. Other adverse events included headache, dry mouth and falls.

About 45% of Alzheimer’s patients suffer from insomnia. Although there are a variety of reasons for that, there are a number of neurotransmitters in the brain that regulate sleep and wakefulness, including the orexin signaling system. Patients with Alzheimer’s disease often have elevated orexin levels in cerebral spinal fluid.

Belsomra is a highly selective antagonist for orexin receptors. It is an oral medication.

“Insomnia and other sleep disturbances are more common in people with Alzheimer’s disease dementia, but evidence for the efficacy and safety of sleep medications in this population remains limited,” stated W. Joseph Herring, associate vice president, Global Clinical Research, Neuroscience, Merck Research Laboratories. “We are encouraged by the efficacy and safety results of Belsomra in those living with Alzheimer’s disease dementia. Merck plans to file these data with the U.S. Food and Drug Administration for potential inclusion into the Belsomra prescribing information.”

According to the Alzheimer’s Association, people with late-stage Alzheimer’s spend about 40% of their time in bed at night awake and sleeping during the daytime. The National Institutes of Health (NIH) encourages non-drug treatments first, such as maintaining regular meal and bedtimes, morning sunlight exposure, avoiding alcohol, caffeine and nicotine, for example.

Sleep medications in Alzheimer’s patients are associated with an increased risk of falls and other issues. Other types of drugs used to treat sleep changes in Alzheimer’s patients include tricyclic antidepressants like nortriptyline and trazodone, benzodiazepines like lorazepam and oxazepam, and sleeping pills such as zolpidem and chloral hydrate. In some cases, “atypical” antipsychotics like risperidone, olanzapine and quetiapine are tried.

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