Sleep Aid with Novel Mechanism Approved

August 1, 2005

Pharmaceutical Executive

Pharmaceutical Executive, Pharmaceutical Executive-08-02-2005, Volume 0, Issue 0

Experts offer their opinion on how Takeda's Rozerem, the first non-controlled sleep aid, will be received by doctors and patients.

A new insomnia treatment, approved by FDA July 22, is the first insomnia drug that was not designated a controlled substance by the Drug Enforcement Agency. Rozerem (ramelteon) is also the second sleep aid indicated for long-term use. Sepracor’s Lunesta (eszopiclone) was the first.

Predicted Patient Reaction:

One of key questions about Rozerem is what its lack of a DEA warning will mean for the insomnia drug market.

    The fact that Rozerem is not controlled would not affect physicians’ prescribing behavior at all, predicted Dr. Clifford Massie of Chicago’s Suburban Lung Association. But he added that it might make a difference to patients with concerns about taking insomnia drugs.

    It will help eliminate patients’ fears of a stigma associated with sleep aids, Dr Rafael Pelayo of the Stanford Sleep Disorders Clinic said. This will make more people comfortable talking to their doctors or pharmacists about getting treatment, he continued.

    Pelayo attended an advisory board meeting for Rozerem at Takeda. He has also sat on advisory boards for competitor drugs Ambien and Lunesta.

    Both doctors said that Lunesta’s indication for long-term use would also make patients more comfortable with seeking treatment.

    “It’s good news for patients to know that insomnia has gotten safer,” Pelayo said.

Doctor’s Reaction:

New sleep drugs usually have variable results on patients, Massie said. He noted that many insomnia patients at specialty clinics have been on medication for so long that it is difficult to predict how their brains will a new receive treatment.

    But he noted concerns that Rozerem was too short acting to provide a full night of sleep.

    “What we really need is something that zonks people out for eight hours and then has no carry over,” Massie said.

    Pelayo wondered about the possibility of combining Rozerem with other insomnia therapies.

How It Works:

Rozerem has an affinity for two types of melatonin receptors, labeled MT1 and MT2, which are found in a part of the hypothalamus called the suprachiasmatic nucleus, or SCN, according to Phyllis Zee, an associate professor of neurology at Northwestern University’s Feinberg School of Medicine.

    The SCN functions as a master clock of circadian rhythms – the biological cycles that humans undergo on a 24-hour basis, Zee said. One of the master clock’s jobs is to produce a signal that keeps people awake during the daytime. The longer a person is awake, the stronger the signal, peaking at about 9 p.m. This acts to counteract the body’s natural drive for sleep.

    Without this signal people would be taking short naps every three or four hours, Zee explained. It allows people to consolidate their sleep at night.

    Although there is no direct proof, Zee indicated that experts believe Rozerem works by decreasing the rate at which the SCN fires off this signal. This is the same effect that melatonin has in controlled lab experiments, she said. But results of small studies on people using melatonin are not consistent with each other, she continued.

    Other insomnia drugs act on different sleep centers in the brain, located in both the hypothalamus and the cortex, Zee said. They interact with receptors for neurotransmitter GABA.

    Zee was an investigator for a multi-center clinical trial of Rozerem.

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