Patient Unmet Needs and Pipeline Developments in Fibromyalgia
Fibromyalgia is a chronic, heterogeneous pain condition primarily driven by sensitization of the central nervous system (CNS). Its symptoms include joint stiffness, chronic pain at multiple tender points, cognitive dysfunction, sleep disturbances, anxiety, fatigue, and depressive episodes. It has a 1.3–8% prevalence in the general population and is significantly more common in females. Additionally, individuals with fibromyalgia are 8.5 times as likely to have a relative diagnosed with fibromyalgia than those without.
Both diagnosis and treatment are difficult, as there are no gold standard criteria and supportive laboratory findings for diagnosis—treatment is currently symptom management with few FDA-approved drugs.
Patient unmet needs include improving diagnostic capabilities through biomarkers, increasing efficacy, and decreasing side effects of Fibromyalgia pharmacotherapeutics.
Cannabinoid receptors in the early stages of development and serotonin receptors in the late stages of development show significant promise in treating Fibromyalgia.
The pathophysiology of Fibromyalgia is unclear, but many pathways are implicated.
Fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission, and processing of afferent nociceptive stimuli. Pathogenesis of Fibromyalgia is still unclear but has been linked to other factors such as inflammatory, immune, endocrine, genetic, and psychosocial factors. The main alterations observed are related to dysfunctions in mono-aminergic neurotransmission, leading to elevated levels of excitatory neurotransmitters such as glutamate and substance P, and decreased levels of serotonin and norepinephrine in the spinal cord at the level of descending anti-nociceptive pathways. Other anomalies observed are dopamine dysregulation and altered activity of endogenous cerebral opioids. Other possible causes identified are peripheral pain generators that may cause increased nociceptive tonic supply in the spinal cord.
Diagnosis remains difficult, and current therapeutics are few and focused on symptom management.
As the pathology of the disease is not well characterized, and there is still debate on how Fibromyalgia is diagnosed, as many as 75% of afflicted individuals remain undiagnosed. There are no specific tests for Fibromyalgia—however, the condition is characterized by the widespread pain index and symptom severity score that measures many symptoms. The American College of Rheumatology gives the following criteria for a Fibromyalgia diagnosis:
Pain and symptoms over the past week, based on the total number of painful areas out of 19 parts of the body plus the level of severity of these symptoms: fatigue, waking unrefreshed, cognitive (memory/thought) problems, and other general physical symptoms.
Symptoms lasting at least three months at a similar level.
No other health problems that would explain the pain or other symptoms.
Current pharmacological treatment is focused on symptom management, as no therapies have been conclusively proven to treat Fibromyalgia. To date, FDA approved 3 drugs for Fibromyalgia with varying degrees of efficacy around symptom management, duloxetine (Cymbalta), milnacipran (Savella), and pregabalin (Lyrica). Both duloxetine and milnacipran affect brain chemicals that control pain levels, while pregabalin blocks the overactivity of nerve cells involved in pain. Many patients with Fibromyalgia are treated with off-label drugs such as antidepressants due to the lack of highly effective FDA-approved drugs. Current ACR guidelines unanimously advocate pharmacological treatment with complementary modalities like exercise and cognitive behavioral therapy. Preventative treatments to address risk factors/triggers are also utilized.
Significant patient unmet needs remain in Fibromyalgia.
There is a lack of gold standard criteria and supportive diagnostic laboratory findings. Diagnosis usually follows a physician interview and a patient meeting ACR criteria with no other physical explanations for their symptoms. While physiological changes have been identified in Fibromyalgia patients, such as clinical studies that have confirmed a central neuronal alteration in nociceptive processes through fMRI, no tests exist to diagnose Fibromyalgia. Identifying biomarkers or similar laboratory findings would allow for earlier diagnosis, improving patient outcomes.
Treatment of Fibromyalgia is currently based on individual symptom management. Furthermore, patients often discontinue treatment for both on-label and off-label medications due to significant side effects and lack of efficacy. Of those treated with pharmacotherapy, a 50% reduction in pain intensity is generally achieved by 10–25%, a 25–40% pain reduction is granted, and meaningful relief occurs in 40–60% due to dose limitations and incomplete efficacy.
The pipeline is relatively small and driven by mid-sized companies.
Source data: Evaluate Pharma 2023The pipeline contains 21 products from pre-clinical to filed, with most in the early stages (preclinical to phase 2). Of these products, the most common MoAs are related to cannabinoid receptors and serotonin receptors, with cannabinoid receptors more common in earlier phases and serotonin receptors spread throughout the pipeline. These mechanisms primarily focus on pain management but not disease modification. Most of the pipeline products are being developed by mid-sized biopharma companies. Tonix Pharma, Vitris, and Daiichi Sankyo are the most active companies in this space.
Author: LizAnn Sung
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