Breakthrough Clinical Results
Encoded Therapeutics announced preclinical data for its AAV9 microRNA (miRNA) gene therapy candidate targeting SCN9A (NaV1.7) for chronic pain. The data demonstrated robust knockdown of SCN9A in non-human primates, exceeding therapeutic thresholds observed in rodent pain models. The candidate is designed for selective and durable knockdown of SCN9A, a key mediator of pain sensitivity, via intrathecal delivery of AAV9 to dorsal root ganglia (DRG) neurons. The company is advancing the program towards development in 2026, with the goal of providing a one-time, non-opioid therapy for intractable chronic pain.
Key Highlights
- AAV9 miRNA gene therapy candidate achieved robust knockdown of SCN9A (NaV1.7) in non-human primates.
- Target engagement levels in NHPs exceeded therapeutic thresholds for pain relief established in rodent models.
- The candidate is designed for selective knockdown of SCN9A in DRG sensory neurons via intrathecal delivery of AAV9.
- Program advancing toward development in 2026 as a one-time, non-opioid therapy for intractable chronic pain.
Incidence and Prevalence
Global Prevalence and Incidence of Chronic Pain: Latest Estimates
Global Prevalence Estimates
The prevalence of chronic pain varies significantly across different populations and regions globally, with estimates ranging from 8% to 80% according to different studies. Recent research provides more specific figures:
A 2024 systematic review and meta-analysis on pediatric chronic pain in low- and middle-income countries (LMICs) estimated an overall pooled mean of 8% across all studies, with specific rates for: - General/multi-site/any pain (20%) - Musculoskeletal pain (9%) - Abdominal pain (7%) - Headache (4%) - Fibromyalgia (3%)
In the United States, a 2024 study found that 27.1% of adults met the definition of chronic pain based on National Health and Nutrition Examination Survey (NHANES) data.
A 2021 study reported chronic pain prevalence at 11% to 19% of the adult population globally.
Regional Variations
Regional prevalence estimates show considerable variation: - Norway (2005): 24.4% general population prevalence, with 65% of those affected experiencing pain for over 5 years - Peru (2023): 38.5% (95% CI: 33.5-44.0%) among adults in metropolitan Lima - Benin (2015): 39.2% (CI95%: 29.3-34.7) general population prevalence - Brazil (2020): 30.0% among older adults - Asia-Pacific region: Prevalence ranges from 12% to 45% - Europe: A survey showed chronic pain in 19% of participants
Demographic Patterns
Gender differences are consistently observed: - A Norwegian study found prevalence of 36% (95% CI 34-38) among women and 25% (95% CI 22-26) among men - A Danish study reported a female to male ratio of 1.8:1 for chronic pain
Other demographic factors associated with higher chronic pain prevalence include: - Older age - Lower education levels - Unemployment or being pensioned - High BMI - Low income - Smoking
Special Populations
Certain populations show notably higher prevalence: - Women with HIV: 31.2% (95% CI, 24.6%-38.7%) according to a 2022 systematic review - People with opioid use disorder: 44.0% (95% CI: 40.0-49.0%) based on a 2024 systematic review - University workers in Brazil: 61.4% prevalence, significantly higher among women
Incidence Data
Limited incidence data from a 2019-2020 US National Health Interview Survey showed: - Among pain-free adults in 2019, incidence rates of chronic pain in 2020 were 52.4 cases per 1000 person-years - High-impact chronic pain incidence was 12.0 cases per 1000 person-years
Common Pain Locations
The most frequently reported pain locations include: - Lumbar/lower back: Reported as the most common site in multiple studies - Head: 26.7% in a Brazilian study - Limbs: 13.3% in a Brazilian study - Musculoskeletal pain: Represents approximately 50% of chronic pain cases
Key Unmet Needs and Targeted Populations for Chronic Pain
Chronic pain remains a critical, unmet public health challenge affecting an estimated 20.9% of US adults (51.6 million people) in 2021. Despite its prevalence, there are significant gaps in treatment approaches and specific populations requiring targeted interventions.
Unmet Treatment Needs
Current treatment options have limitations, creating a significant need for innovative solutions and identification of new pain medicines. Pharmacological interventions for chronic pain are not always useful or safe for long-term use, with opioids remaining the analgesic mainstay for severe pain despite significant adverse effects. The clinical development of novel pain medicines with minimal side-effect profiles is an urgent need to address this public health issue worldwide.
Non-pharmacological interventions show promise but face implementation challenges: - Psychological interventions produce modest effects on average with variable efficacy - Digital therapeutics are emerging but primarily reach non-Hispanic White, female, and educated populations - Public awareness of options like mindfulness-based stress reduction (MBSR) remains low - Cost has been identified as a major barrier to implementing new services
Targeted Populations
Several specific populations are being targeted for chronic pain interventions:
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Elderly/geriatric patients (25-50% of elderly living at home suffer from chronic pain)
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Face concerns with anti-inflammatory drugs including renal toxicity
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Often have multiple medical problems limiting treatment options
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Nursing home residents (45-80% suffer from chronic pain)
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Cancer patients
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Being studied for specific interventions like α-tocopherol for chemotherapy-induced peripheral neuropathy
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Benefiting from outpatient palliative care approaches
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Patients on chronic opioids
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Targeted for opioid reduction strategies while improving pain and function
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Racially minoritized populations, particularly Black adults
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Pain care characterized by misconceptions, biases, and discriminatory practices
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Require equity-focused approaches in pain screening and treatment
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Individuals with intellectual disabilities (pain may be under-recognized and under-treated)
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Asia-Pacific region patients
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Prevalence ranges from 12% to 45%, primarily musculoskeletal pain
Research and Implementation Gaps
Research highlights the need for: - Better integration of various treatments and multidisciplinary approaches - Large registries to record patient characteristics, treatments, and outcomes - Understanding the role of therapist-related factors in treatment outcomes - Improved education regarding risks, treatment options, and appropriate facilities - Better clinical guidelines for chronic pain management - Addressing social determinants of health that impact pain treatment
The economic burden of chronic pain is substantial, with yearly costs estimated at 4% of GDP, with 80% attributed to productivity loss, underscoring the urgency of addressing these unmet needs.
Recent Studies
Recent Studies for Chronic Pain: Interventions and Outcomes
Digital Interventions for Chronic Pain (2024)
This multisite, randomized trial compared digital cognitive behavioral therapy (CBT) with a digital pain/SCD education program for managing pain in sickle cell disease (SCD). Both interventions used an app with interactive chatbot lessons and personalized health coach support over 12 weeks.
Efficacy outcomes: Both groups showed significant within-group improvements in pain interference (CBT: -2.13; Education: -2.66), but no significant difference between groups. No between-group differences were found in pain intensity, depression, anxiety, or quality of life.
Safety outcomes: No specific safety concerns were reported.
Pain Management with Extended-Release Buprenorphine (2025)
This scoping review evaluated pharmacologic pain management strategies for patients prescribed extended-release buprenorphine (BUP-XR) for opioid use disorder experiencing pain.
Efficacy outcomes: Effective strategies included continuation of BUP-XR with combination of full opioid agonists and non-opioid adjuncts, adjunct use of nonsteroidal anti-inflammatory drugs, conversion to sublingual buprenorphine, and performing surgery at trough serum buprenorphine concentration.
Safety outcomes: No cases of respiratory depression or toxicity were observed.
CBD and Multi-Modal Exercise for CIPN (2023)
This study explored the effectiveness of cannabidiol (CBD) alone and in combination with multi-modal exercise (MME) for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.
Efficacy outcomes: After 2 months of CBD alone, positive effects were observed for CIPN neurotoxic symptoms, perceived physical function, and hand grip strength. After adding MME to CBD for another 2 months, improvements were seen in painDETECT scores, CIPN neurotoxic symptoms, perceived physical function, overall quality of life, gait speed, and manual dexterity.
Safety outcomes: No specific safety concerns were reported.
Duloxetine for Painful Diabetic Peripheral Neuropathy (2021)
This systematic review and meta-analysis compared duloxetine and placebo for painful diabetic peripheral neuropathy (PDPN).
Efficacy outcomes: Duloxetine was more efficacious than placebo for pain improvement (mean difference -0.89; 95% CI -1.09 to -0.69; P<.00001) and significantly improved patients' quality of life. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms.
Safety outcomes: No specific safety concerns were reported in this review.
Transcranial Direct Current Stimulation (2023)
This study on transcranial direct current stimulation (HD-tDCS) in healthy adults evaluated its effects on endogenous pain modulation.
Efficacy outcomes: The study demonstrated effectiveness on endogenous pain modulation.
Safety outcomes: No adverse events were reported.