An FDA advisory panel has voted in favor of condoliase, an intervertebral injection for the treatment of radicular leg pain associated with lumbar disc herniation (LDH). The Anesthetic and Analgesic Drug Products Advisory Committee voted 8-4 in support of the drug's approval, noting that its benefits outweigh the risks when used to treat radicular leg pain caused by confirmed nerve root impingement in adults. If approved, condoliase would be the first biologic or drug specifically approved for lumbosacral radicular pain.
Addressing an Unmet Need
Patients with radicular leg pain often seek relief from various therapies, including nonpharmacologic, off-label pharmacologic, and device-based treatments. When these conservative approaches—such as physical therapy, NSAIDs, acetaminophen, neuropathic pain drugs, systemic steroids, spinal cord stimulation, and percutaneous discectomy—fail, some patients resort to surgery. Condoliase offers a potential alternative, particularly for those who may not be suitable candidates for surgery or who wish to delay it.
"Condoliase does address an unmet need in patients who haven't responded to conservative therapy," said Mark Bicket, MD, PhD, of the University of Michigan in Ann Arbor, who voted in favor of the approval. He cited two positive trials on condoliase as sufficient evidence of treatment efficacy.
Trial Data and Patient Selection
The panel emphasized that the proposed indication for condoliase may be too broad. The evidence suggests efficacy in the short term within a specific population experiencing lumbosacral radicular pain. Participants in the pivotal Study 1133 trial had to meet strict criteria, including:
- Contained posterolateral LDH at either L4-5 or L5-S1 (or L5-6) with root impingement on MRI
- A primary complaint of unilateral radiculopathy or radicular leg pain in the concordant dermatome of the affected nerve root
- Failure of at least 6 weeks of conservative treatment, including medications, physical therapy, chiropractic treatment, acupuncture, spinal injection, epidural injection, or nerve block
- Exclusion of other disorders associated with low back pain, chronic pain disorder, peripheral neuropathy caused by diabetes, a history of substance abuse, or concurrent anticoagulant therapy
The 352-person Study 1133, conducted in the U.S., demonstrated that condoliase (a single 1 mL injection at varying concentrations) significantly improved average leg pain from baseline to week 13, as assessed by the Visual Analog Scale, compared to a sham injection outside the disc. This trial incorporated stricter entry criteria compared to a previous trial, which had failed to meet its efficacy endpoint due to a more heterogeneous patient population.
Concerns and Considerations
Despite the positive vote, panelists raised concerns about potential safety issues. One significant concern is the risk of immune-related adverse events, including severe cutaneous adverse reactions (SCAR). Postmarketing data from Japan, where condoliase has been available since 2018, suggest a SCAR frequency of approximately 1 in 1,500 to 1 in 2,000 patients.
"I am concerned. I could envision in the next few years, a million people might get this therapy ... a few hundred of these [SCAR] cases in the U.S. would likely cause the FDA to think twice about continuing approval," said Steven Schiff, MD, PhD, of Yale University.
Another concern is the potential for long-term spinal changes resulting from the removal of chondroitin sulfate, which could lead to decreased disc height, reduced spinal mobility, and the development of bony growths. These changes may increase the risk of axial back pain or affect future surgical options.
Mechanism of Action
Condoliase is a biological product derived from Proteus vulgaris that reduces disc volume and relieves pressure on the lumbar spinal nerve root. It degrades chondroitin sulfate, a major component of the nucleus pulposus of the intervertebral disc.
Current Landscape
Radicular leg pain, a type of neuropathic pain, often results from pressure on a lumbar spinal nerve root, commonly caused by LDH. While acute radicular pain due to LDH often resolves spontaneously or with conservative management, 15% to 40% of patients with new-onset lumbar radiculopathy experience chronic pain or relapse.
The Path Forward
While the FDA is not bound to follow the advice of its advisory committees, it typically does. If approved, condoliase would offer a novel treatment option for a select group of patients with radicular leg pain due to LDH who have not responded to conservative therapies. Careful patient selection, monitoring for adverse events, and long-term data collection will be crucial to ensure its safe and effective use.
