by Duncan McHale, Chief Medical Officer, Persica Pharmaceuticals
Despite advances in imaging techniques chronic Low Back Pain is generally treated as a single condition with 80% of cases being classified as non-specific. Patients are grouped together and offered a similar sequence of options: exercise and physiotherapy, analgesics, and then – for those who do not respond – escalating interventions that range from opioids to epidural injections and ultimately to surgery. This approach has produced a large amount of clinical trial data, many failed therapies and comparatively little clarity, because chronic low back pain is not one condition. It is a symptom that arises from a wide range of underlying causes with little in common beyond where the patient feels the pain.
Vertebrogenic Lumbar Back Pain (vLBP) is one sub-group of patients that is now distinct enough to be treated as its own diagnosis rather than a subset of this much larger, undifferentiated population.
Identifying the condition
vLBP is associated with a specific finding on an MRI scan: Modic changes, first described by Michael Modic in 1988 as alterations in the vertebral end plate and bone marrow adjacent to the intervertebral disc. Modic type 1 changes reflect oedema and inflammation in the vertebral endplate; type 2 changes reflect a later, fatty infiltration of the marrow. Both are visible on standard MRI sequences and can be identified reliably by a radiologist or, in a trial setting, by a central imaging reader, meaning vLBP can be diagnosed rather than inferred. A clinician does not need to rely on a patient’s history and a process of elimination. They can look at a scan and see the finding that defines the condition.
Of patients with chronic low back pain, a meaningful proportion (by our estimate around 15 percent) have moderate-to-severe pain associated with Modic changes. Across the United States and Europe combined, that points to a population in the order of 10 million people, most of whom have already tried and failed several rounds of treatment before anyone even establishes the presence of Modic changes and the diagnosis of vLBP.
In 2022, an MRI-based diagnostic code for vertebrogenic back pain was introduced into the US ICD-10-CM system confirming the clinical importance of identifying this sub-group of patients. Formal coding recognition of this kind happens when conditions have been shown to have a distinct clinical presentation, a reliable diagnostic marker and a rationale for a distinct treatment pathway. In practical terms, it means clinicians, payers and regulators now have a shared language for vLBP that did not exist a decade ago.
A precision approach to addressing pain
A precise diagnosis can change everything for patients, physicians and drug development. If a treatment is designed to address a specific mechanism, and it is tested in a population selected for that mechanism, the resulting data will be more interpretable than if the trial includes a mixed population in which only a fraction of patients have the right pathology. This approach has been pioneered in oncology, but has been under-utilised in chronic pain, where trial populations have generally been defined by symptom duration and severity rather than by underlying cause.
In parallel with the recognition of vLBP as a distinct sub-type of chronic low back pain, there has been the emergence of an evidence base demonstrating that a major cause of the Modic changes is a low bioburden chronic infection. Oral antibiotics have been shown to improve the pain in vLBP if given at a high dose and for a prolonged 100 day period. Oral antibiotics are not a routine solution due to their limited penetration into the disc space, adverse event profile, and concerns around antibiotic resistance with prolonged systemic exposure.
This is the premise behind PP353, Persica’s intradiscal treatment for vLBP. PP353 is a targeted treatment, delivered locally to the disc in patients selected on the basis of MRI-confirmed Modic changes, treating the infection which is driving the pain rather than just the symptoms.
Compelling clinical data
Persica’s Phase 1b clinical trial enrolled patients with vLBP who had not responded to conservative care, most having lived with the condition for five years or more. Two intradiscal doses of PP353 were compared with two sham procedures given 4 days apart. At the 12-month primary endpoint, the trial showed a statistically significant and clinically meaningful difference between PP353 and the control group in patient-reported pain, alongside improvements in disability scores, using pre-specified analyses. More than 60 percent of patients receiving PP353 achieved at least a 50 percent improvement in pain and disability at 12 months, a durable effect rather than a transient one. The treatment group also recorded a 94 percent reduction in opioid use days and a 42 percent reduction in use of non-opioid analgesics over the same period, with no meaningful difference in adverse events compared with the sham control group.
These are Phase 1b results – and they need to be confirmed in larger, registrational studies. But they illustrate something important: when a trial population is defined by a diagnostic marker rather than by symptom criteria alone, the resulting data are considerably easier to interpret and considerably more encouraging.
A distinct condition, a distinct opportunity
The broader point is one about how chronic pain drug development should proceed. vLBP is now diagnosable, its prevalence is substantial, and it has a regulatory and coding framework that recognises it as distinct. It is a tractable target rather than another entry in the long list of chronic pain indications that have shown disappointing data in late-stage trials.
The next step for PP353 will be larger scale registrational studies to rigorously generate the evidence required to get this potentially disease modifying treatment approved for the millions of patients who suffer with this debilitating and disabling illness.
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