There is a devastating opioid use and overdose crisis in the United States. It has been reported that approximately 25.5 million adults suffer pain and opioids that are often prescribed for their treatment can lead to opioid misuse and dependence. It has also been reported that more than 2 million Americans have OUDs and many started their addiction with prescribed opioids. One of the most devastating consequences of opioid misuse is opioid overdose, which can produce respiratory depression and death. Drug overdose is the leading cause of accidental death in the US, with an estimation of 60,000 deaths in 2016; 20,101 overdose deaths related to prescription pain relievers, and 12,990 overdose deaths related to heroin.
Although there are safe and effective pharmacotherapies for opioid use disorders and to prevent/reverse overdose, their use has some limitation or they are largely underutilized. Methadone and buprenorphine are approved by the FDA to treat OUDs but long term efficacy and treatment adherence are sub-optimal. Naltrexone is approved by the FDA to prevent opioid use relapse in people with no physical dependence to opioids but initiation and adherence to treatment are low. Naloxone is approved to reverse opioid overdose but it has a short action, may precipitate opioid withdrawal, and put the person at risk of overdose.
Currently, there are no medications approved by the FDA for the treatment of opioid withdrawal (including medications to treat the opioid withdrawal of neonates born to mothers with OUDs). Lofexidine is being investigated for the treatment of opioid withdrawal and is pending review by the FDA to determine its approval. Other medications such as gabapentin, pregabalin, buprenorphine, cannabinoids, ketamine, and ultra-low doses of oral naltrexone, as well as rapid opioid withdrawal under anesthesia have been evaluated but the results are inconclusive.
Advances in the understanding of OUDs, overdose, and pain may provide new pharmacological opportunities to improve the treatment of these disorders and contribute to reduce the current opioid use crisis. Some of these advances include the new findings of receptors, neurotransmitters, neuromodulators, and brain circuits associated with OUDs, a greater understanding of the endogenous opioid system, and the risk and protective factors for the onset and progression of these disorders. New targets and medications, new formulations and delivery systems of medications may be ready to be evaluated. Better understanding of pain mechanisms has revolutionized our understanding of addiction and pain and new, non-addictive pain medicines are urgently needed to prevent the initiation or progression of OUDs and prevent overdoses. Furthermore, advances in the development of biologics can offer an opportunity to investigate vaccines and monoclonal antibodies for the treatment of OUD and overdose.
Buprenorphine treatment, given its partial agonist effects, may offer a unique pharmacological opportunity to reduce the lethality of opioid overdose. Relapse prevention with the opioid antagonist naltrexone may also reduce the risk of overdose. The FDA will soon be reviewing the NDA of weekly and monthly injections of buprenorphine which appear to improve treatment adherence and hopefully improving outcomes including preventing opioid overdoses.
There is an urgent need to accelerate the development and obtain FDA approval of medication to prevent and treat OUDs and overdose. Multiple therapeutic approaches may be poised for the next step in the FDA approval process and concerted efforts are needed to advance these potential pharmacotherapies to approval. New scientific advances in this area offer unprecedented opportunities to develop these types of medications. The purpose of this Funding Opportunity Announcement is to support studies that will evaluate the safety and efficacy of medications to prevent and treat OUDs and overdose.
The goal is to support preclinical and clinical research studies that will have high impact and quickly yield the necessary results to advance closer to FDA approval, medications that are safe and effective to prevent and treat OUDs and overdose.
- Applications submitted in response to this FOA should focus on studying:
- New chemical entities (NCEs)
- Medications already marketed for other indications
- Biologics (vaccines, monoclonal antibodies)
- Combination of medications
- Pre-clinical studies
- FDA Phase I, II and III clinical trials
Compounds may be developed for indications such as:
- Prevention of initiation of OUDs.
- Prevention of progression of the severity of OUDs.
- Reduction of the dose of opioids analgesics
- Improvement OUD treatment adherence
- Facilitation of opioid agonist discontinuation
- Treatment of opioid withdrawal
- Treatment of neonatal opioid withdrawal
- Reduction of opioid tolerance
- Reduction of lethality of opioid overdose
- Reduction of overdose relapse
- Reduction of the risk of opioid respiratory depression
Applications focusing solely on novel target identification/validation, generation of new animal models, development/testing of new human laboratory models, or mechanistic studies of the neurobiology of addiction are considered not responsive for this FOA and may be withdrawn.
Deadline: Applications will be accepted on a rolling basis, beginning on January 25, 2018. Letters of intent are due 30 days prior to the submission of a full proposal.
Filed Under: Funding Opportunities