Idorsia Pharmaceuticals filed a Citizen Petition with the Drug Enforcement Administration (DEA), urging them to de-schedule the dual orexin receptor antagonist (DORA) class of chronic insomnia medications based on data indicating a low potential for abuse.

The petition outlines scientific and medical evidence demonstrating that the DORA class has a negligible abuse profile and potential for abuse, lacks non-medical use in the community, lacks physical and psychological dependence, and therefore, should not be a scheduled class under the Controlled Substances Act. 

Among the most commonly prescribed medicines that are approved to treat insomnia are benzodiazepines and Z-drugs (including zopiclone, eszopiclone, zaleplon, and zolpidem). These drugs are recommended for short-term use with frequent re-evaluation and, due to the risk of dependence and misuse and abuse, are scheduled as Schedule IV under the Controlled Substances Act. 

The Schedule IV classification of the DORA class puts them in the same classification as benzodiazepines and Z-drugs; however, the DORA class works differently, blocking signals in the brain that stimulate wakefulness addressing chronic insomnia without creating dependence and with a negligible potential of abuse, according to a press release by Idorsia. 

“Given the rising cases of substance abuse disorder with certain prescription medications in the United States, I’m pleased to see data from the DORA class, which shows the negligible abuse potential of DORAs when treating insomnia,” says Vaughn McCall, MD, professor and case distinguished chair of the department of psychiatry and health behavior at Augusta University, in a press release. “I am hopeful that the DEA will consider de-scheduling the DORA class as it is critical in preventing the overuse of other medications, which may be abused or misused, to treat insomnia.”

The petition requests that the DEA administrator initiate a rulemaking proceeding to remove the DORA class medications from scheduling under the Controlled Substances Act based on the following three points:

  • Eight years of post-marketing surveillance data suggests that the DORA class has an insignificant risk of abuse profile and potential for abuse, lack of non-medical use in the community, and similar lack of physical or psychological dependence.
  • Based on major federal surveillance systems including US Food and Drug Administration’s Adverse Events Reporting System, the rates of abuse and dependence-related reports, serious adverse events, and adverse events requiring hospitalization associated with the DORA class are extremely low in incidence and substantially lower than rates for Schedule IV benzodiazepines and related drugs, including those sometimes referred to as “Z-drugs” (namely zopiclone, eszopiclone, zaleplon and zolpidem).
  • A re-analysis of the Eight Factors of the Controlled Substances Act (a required step in the scheduling process) supports the removal of the DORA class from scheduling under the Controlled Substance Act.

“Idorsia is asking the DEA to de-schedule the DORA class as part of our continued commitment to treating insomnia,” says Jean-Paul Clozel, MD, CEO of Idorsia, in a press release. “As there is significantly more data and evidence on the DORA class today than when these drugs were first approved in 2014, we believe that the DEA should reconsider its decision to schedule these drugs, considering they have negligible abuse profiles and potential for abuse. Access to the DORA class of medicines for insomnia should not be limited by the constraints put in place to manage and restrict the use of scheduled drugs or controlled substances.”

DORAs block the activity of orexin; they “turn down” overactive wakefulness pathways, in contrast to insomnia treatments which act via general CNS sedation. DORAs specifically target the orexin system by competitively binding and antagonizing both orexin receptors, thereby reversibly blocking the activity of orexin. 

Blocking orexin receptors reduces the downstream activity of the wake-promoting neurotransmitters that are overactive in insomnia. As a result, orexin receptor antagonism targets the fundamental mechanism of insomnia and does not activate dopamine neurons, thus representing much lower risks of abuse, dependence, and overdose than conventional Schedule IV drugs used to treat insomnia, according to a press release by Idorsia.

A Citizen Petition can be filed to ask that a governing agency, like the DEA or US Food and Drug Administration, take or refrain from taking a particular action. Any person may file a Citizen Petition, and any person may comment on a petition that has been filed. Idorsia cannot predict when or if the DEA will respond to or otherwise take any action concerning the Citizen Petition filed.