New draft guidelines suggest the FDA is open to exercising regulatory flexibility for non-opioid drugs being developed for chronic pain.
The FDA has signaled its openness to accelerating the development of new, non-opioid analgesic treatments for chronic pain in a new draft guidance.
“In certain circumstances, it may be possible to decrease the number of trials required” for a drug developer to seek approval for their pain medication, according to the document, published Wednesday. Broadly speaking, sponsors must typically run at least two well-controlled trials to provide sufficient evidence for their candidates.
But for non-opioid painkillers for chronic pain, the agency is considering allowing the use of just one “single adequate and well-controlled” study, plus confirmatory evidence, as the basis for an application.
Such a change, according to the FDA, will “increase the efficiency of an analgesic development program.”
The guidance is open to commentary until Nov. 10, according to the Federal Register.
“We sense a high degree of FDA interest in helping sponsors develop non-opioid approaches,” analysts at Jefferies said in a note to investors on Wednesday. The firm expects many early-stage biotechs in this space—including Xenon Pharmaceutials and Rapport Therapeutics—to explore these new streamlining strategies proposed by the FDA.
Of note, the FDA will require these proposed painkillers to have “strong scientific justification” for their indication. That is, the drug candidates should have a mechanism of action that is “both clearly understood and shown to directly target the major driver” of pain pathophysiology. Companies should also be able to demonstrate that their investigational drugs are safe, including a “thorough assessment of abuse and misuse potential.”
The FDA’s draft guidance also appears to open the door to the use of biomarkers to establish efficacy.
While the agency explicitly indicated that it would be “difficult” to rely on surrogate or intermediate endpoints—as is the case for drugs accepted into its accelerated pathway—companies are nevertheless encouraged to explore “potential biomarkers” that could allow their candidates to qualify for “an expedited program.” These include the FDA’s fast track, priority review or breakthrough designations.
These draft guidelines come after the landmark approval of Vertex Pharmaceuticals’ Journavx in January, opening up a new mechanism of acute pain treatment for the first time in decades. The drug works by acting on sodium ion channels and prevents the transduction of pain signals back to the central nervous system.
Notably, however, Journavx is indicated for use in acute pain, whereas the FDA’s document explicitly applies to therapies in development for chronic pain.
Journavx’s approval has energized the pain space, and many biotechs are looking to follow in its footsteps. One of these is Lexicon Pharmaceuticals, which is advancing pilavapadin, an oral small-molecule drug designed for neuropathic pain. Also in the space is Sangamo Therapeutics, which is addressing pain via its gene editor ST-503, which targets a gene that encodes for an ion channel protein.
