SILVER SPRING, Md. -- An FDA advisory committee voted to approve lofexidine, a novel non-opioid drug intended to treat symptoms of opioid withdrawal and help patients halt opioid use, during a meeting here.
In votes of 12-0 and 11-1, the backed approval for relieving opioid withdrawal symptoms in physically dependent patients who abruptly stop opioids and for keeping them in withdrawal treatment.
If the FDA follows its committee's votes, lofexidine would become the first non-opioid medication approved to treat opioid withdrawal and the first drug approved to help patients successfully terminate their opioid discontinuation treatment. Developed by Lexington, Ky.-based , its proposed trade name is Lucemyra.
The FDA is not obliged to follow its advisory committees' recommendations but it usually does.
"Of course we're excited," Kristen Gullo, US WorldMeds' vice president of development and regulatory affairs, told ľֱ.
"suppresses the neurochemical surge that produces the acute and painful symptoms of opioid withdrawal," according to a company . It is an alpha-2 adrenergic agonist -- similar to clonidine, which FDA staff noted is often used off-label for opioid withdrawal symptoms -- slated to be part of a long-term treatment plan when patients stop using opioids.
"It's not a solution to the overall opioid epidemic, but it is a missing piece," Gullo said.
The committee seemed to agree, voting 12-0 supporting the primary indication of lofexidine treating opioid withdrawal symptoms. "No question," said Michael Proschan, PhD, a statistician with the National Institute of Allergy and Infectious Diseases.
"The data was there," said Rajesh Narendran, MD, a University of Pittsburgh psychiatrist who chairs the committee.
The committee then voted 11-1 to support lofexidine's secondary indication, to help patients complete the process of withdrawal from physical opioid dependence.
Several committee members insisted, however, that lofexidine's recommended dosage be limited to 2.4 mg daily -- as opposed to the 3.2 mg dose suggested by US WorldMeds -- and called for post-marketing studies.
"Starting more conservatively probably makes sense," said Kathleen Carroll, PhD, a psychiatry professor at Yale University School of Medicine.
"I still have concerns about 3.2 mg, the safety," Proschan said.
Erick Turner, MD, suggested FDA clearly mark dosage instructions for providers so they don't prescribe 3.2 mg doses. "Clinicians don't read the (standard) labeling," said Turner, an Oregon psychiatrist and psychiatry professor. "Make it clear."
The higher dose could cause more side effects and adverse events, Narendran said, but he reiterated what some committee members suggested, which was to permit clinicians the option of prescribing higher doses at their discretion.
Narendran suggested studying lofexidine's interactions with antipsychotic medications such as mirtazapine (Remeron) and trazodone, which he said many potential lofexidine patients would likely be taking. He also recommended examining tapering lofexidine along with methadone and other medications patients now commonly use for opioid withdrawal.
, the committee's designated consumer representative, was the only member to cast a dissenting vote Tuesday. She opposed lofexidine's secondary indication, saying it lacked a substantial evidence base and that she worried the drug could be marketed in a misleading fashion.
Committee members asked for more data concerning the results of patients taking lofexidine repeatedly. US WorldMeds had recommended stints of 7-14 days and "14 days seems reasonable," Narendran concluded, citing the committee's discussion on the issue.
US WorldMeds expects an FDA decision on lofexidine May 26, Gullo said, and if it is approved, the company plans to launch the drug this summer. The company views the potential launch as "doing something real about the opioid epidemic."
The firm will work with the FDA regarding the dosage labeling suggestion and plans to commission studies on tapering -- especially regarding pediatric programs.
Prior to the meeting, FDA staff had raised concerns about the lack of data on the drug's utility in patients with withdrawal symptoms while tapering opioids, as opposed to abruptly stopping them. The company was not seeking approval for that indication, but the agency was considering possible safety issues with off-label use.
Great Britain approved lofexidine in the mid-1980's to relieve symptoms "in patients undergoing opiate detoxification," with patients in the 1990's typically taking doses between 1.6-2.2 mg for a median of 10 days.