Idorsia Shares Evidence in Citizen Petition to De-Schedule DORA Class Insomnia Drugs

A Citizen Petition was filed with the Drug Enforcement Administration (DEA) in the US by Swiss pharmaceutical company Idorsia Pharmaceuticals to de-schedule the dual orexin receptor antagonist (DORA) class of chronic insomnia medications.¹

“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," Jean-Paul Clozel, MD, Chief Executive Officer, Idorsia, said in a statement.

According to the announcement from Idorsia, the petition argues that DORA medications have a minimal abuse profile and potential for abuse, a lack of non-medical use in the community, insignificant physical and psychological dependence, and as a result, should not be a scheduled class under the Controlled Substances Act.

"Idorsia is asking the DEA to de-schedule the DORA class as part of our continued commitment to treating insomnia,” he continued. “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.”

Approximately 25 million American adults are affected by chronic insomnia, and benzodiazepines and Z-drugs (including zopiclone, eszopiclone, zaleplon, and zolpidem) are commonly implemented interventions for treating this condition. However, these drugs are scheduled as Schedule IV under the Controlled Substances Act with a recommendation for short-term use due to the risk of dependence, misuse, and abuse.

"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," Vaughn McCall, MD, Professor and Case Distinguished Chair of the Department of Psychiatry and Health Behavior at Augusta University, stated.

The DORA class works differently from benzodiazepines and Z-drugs, blocking signals in the brain that stimulate wakefulness, addressing chronic insomnia without creating dependence, and with negligible potential for abuse.

These medications work by blocking the activity of orexin, which turns down overactive wakefulness pathways, in contrast to insomnia treatments that act via general central nervous system 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 overactive wake-promoting neurotransmitters in insomnia. As a result, this addresses the fundamental mechanism of insomnia and does not activate dopamine neurons–bringing much lower risks of abuse, dependence, and overdose than conventional Schedule IV drugs used to treat insomnia.

The Citizen Petition requests that the DEA initiate a rulemaking proceeding to remove the DORA class medications from scheduling under the Controlled Substances Act based on eight years of post-marketing surveillance data. According to the petition, the rates of abuse and dependence-related reports, serious adverse events (AEs), and AEs requiring hospitalization associated with the DORA class are extremely low in incidence and substantially lower than rates for Schedule IV benzodiazepines and related drugs.

It's important to note that a Citizen Petition can be filed to ask that a governing agency, like the DEA or US Food and Drug Administration (FDA), take or refrain from taking a particular action. While any person may file a Citizen Petition, there is no guarantee that the governing agency will respond or take any action concerning the petition filed.

References:

1. Idorsia Files Petition with the Drug Enforcement Administration (DEA) Urging Them to De-Schedule Dual Orexin Receptor Antagonist Class of Insomnia Medications. News release. Biospace. April 4, 2023. Accessed April 4, 2023. https://www.biospace.com/article/releases/idorsia-files-petition-with-the-drug-enforcement-administration-dea-urging-them-to-de-schedule-dual-orexin-receptor-antagonist-class-of-insomnia-medications/