Breakthrough Clinical Results
MIRA Pharmaceuticals announced the successful completion of the single ascending dose (SAD) portion of its Phase 1 clinical trial for oral Ketamir-2, a novel oral therapeutic for neuropathic pain. The trial, conducted in Israel, showed a favorable safety and tolerability profile with no severe adverse effects. The company is now advancing to the multiple ascending dose (MAD) stage of the trial and plans to submit a Phase 2a clinical protocol for neuropathic pain by the end of 2025. Ketamir-2 is a proprietary, orally bioavailable molecule targeting the NMDA receptor, demonstrating superior efficacy in preclinical studies compared to ketamine, pregabalin, and gabapentin. The company is also exploring potential applications in depression, anxiety, PTSD, and localized pain.
Key Highlights
- Successful completion of the Phase 1 SAD portion of the oral Ketamir-2 trial with no severe adverse effects.
- Advancement to the MAD portion of the Phase 1 trial.
- Planned submission of a Phase 2a clinical protocol for neuropathic pain by year-end 2025.
- Ketamir-2 demonstrates superior efficacy and safety compared to existing treatments in preclinical studies.
Incidence and Prevalence
Latest Estimates of Neuropathic Pain Prevalence and Incidence
Global Prevalence Estimates
The epidemiology of neuropathic pain presents significant challenges for researchers and clinicians alike. Current evidence suggests that neuropathic pain affects between 7-10% of the general population, making it a common chronic condition worldwide. However, some studies have reported a more conservative estimate, with an estimated prevalence of 1.5% in the general population according to a 2007 review article.
A 2006 UK study with a corrected response rate of 52% found that while the prevalence of any chronic pain was 48%, the prevalence of pain of predominantly neuropathic origin was 8% in the general population. This study also noted important demographic patterns, showing that individuals with chronic neuropathic pain were significantly more likely to be female, slightly older, no longer married, living in council rented accommodation, unable to work, have no educational qualifications, and be smokers.
Disease-Specific Prevalence
The prevalence varies significantly across different conditions:
- In osteoarthritis (OA), a 2019 study found that 21.7% of patients were highly likely to have neuropathic pain, with an additional 21.7% possibly having neuropathic pain
- In rheumatoid arthritis (RA), the same study reported only 6.1% of patients as highly likely to have neuropathic pain, with 30.6% possibly having neuropathic pain
- A 2016 study using the painDETECT screening tool classified 17.0% of rheumatoid arthritis patients as having likely neuropathic pain and 21.4% as having possible neuropathic pain
- In chronic low back pain with radicular pain (CLBP-RP), a 2019 study detected neuropathic pain components at rates of 65.3% using the DN4 scale and 40.6% using the LANSS scale
- The same CLBP-RP study found neuropathic pain was more prevalent in females (75.4% according to DN4, 52.3% according to LANSS) than males (47.2% according to DN4, 19.4% according to LANSS)
In clinical settings, the prevalence appears higher. A 2006 study at Siriraj Pain Clinic found the prevalence of neuropathic pain among pain clinic patients was 37.8%, with an average patient age of 54 years. Peripheral type neuropathic pain, particularly nerve compression, was identified as the most common type.
Burden and Challenges
The burden of neuropathic pain on patients and healthcare systems is potentially large. Patients experience a poor health-related quality of life and consume a high level of healthcare resources and costs. Despite recent advances, current therapy remains inadequate, and treatment is very difficult. There is a dire need to address challenges in diagnosis and treatment due to the high financial burden and impact on quality of life for both patients and caregivers.
Precise estimation of prevalence and incidence remains difficult because neuropathic pain encompasses numerous disease-specific indications, each with different diagnostic definitions and thresholds. Further research is needed to clarify its epidemiology and inform healthcare policy decisions regarding treatment funding.
Mechanism of Action
Three Most Common Mechanisms of Action in Trials for Unapproved Neuropathic Pain Drugs
NMDAR Antagonism
NMDAR (N-methyl-d-aspartate receptor) antagonists have shown significant promise in treating neuropathic pain. These compounds can reduce hyperalgesia and allodynia in animal models of neuropathic pain caused by nerve injury and diabetic neuropathy. Clinically used NMDAR antagonists like ketamine and dextromethorphan have demonstrated effectiveness in patients with complex regional pain syndrome and painful diabetic neuropathy. However, it's worth noting that patients with postherpetic neuralgia respond poorly to these agents. Current research is focused on identifying NMDAR-interacting proteins and molecular mechanisms to develop drugs that can attenuate abnormal NMDAR activity while maintaining minimal impairment of physiological function.
Glutamatergic System Manipulation
Manipulation of the glutamatergic system represents another major approach in neuropathic pain drug development. Studies have shown that spinal extracellular glutamate levels increase in rats treated with bortezomib, which causes neuropathic pain. mGluR5 (metabotropic glutamate receptor 5) antagonists such as MPEP have demonstrated ability to prevent bortezomib-induced pain and counteract sensory nerve conduction velocity reduction. Additionally, agents that promote the reuptake of glutamate can prevent bortezomib-induced hyperalgesia by maintaining spinal glutamate at basal levels. This approach through the mGluR5 receptor shows considerable promise in treating bortezomib-induced peripheral neuropathy.
Multi-Mechanism Approaches
The third common approach involves multi-mechanism drugs that target several pain pathways simultaneously. These approaches focus on:
- Voltage-gated sodium and calcium channels: Drugs like topiramate modulate these channels to relieve neuropathic pain
- GABA inhibition potentiation: Enhancing inhibitory neurotransmission through GABA pathways to reduce pain signaling
- AMPA/kainate glutamate receptor blockade: Blocking excitatory glutamate receptors to diminish pain transmission
One notable example is KRN5500, a derivative of the antibiotic spicamycin, which produces prolonged reduction in neuropathic pain through novel mechanisms. Compounds like this could serve as markers for the discovery of effective analgesics.
The development of these new drugs aims to address the underlying mechanisms of neuropathic pain rather than just treating symptoms. A key focus is on reducing side effects that currently limit existing treatments, making them more tolerable for long-term use in chronic pain conditions.
Ketamir-2 Clinical Trials Beyond Neuropathic Pain
Based on a comprehensive review of available information, there is no data regarding clinical trials of a ketamine-based formulation called "Ketamir-2" for neuropathic pain or any other indications.
While ketamine itself has been studied for various medical applications including:
- Treatment of agitation in emergency department settings
- Adjuvant treatment for organophosphate and nerve agent exposures
- Acute analgesia in mountain rescue scenarios
- Sedation for patients on extracorporeal membrane oxygenation (ECMO)
- An oral extended-release tablet (R-107) for treatment-resistant depression
The specific formulation "Ketamir-2" does not appear in any of the reviewed clinical trial information. Consequently, there is no information available regarding:
- Phase I, Phase II, or Phase III studies for this product
- Intervention models or methodologies for clinical trials
- Dosing regimens or administration protocols
- Additional indications beyond neuropathic pain
Without confirmed clinical trial data, it is not possible to provide details about alternative indications or intervention models for Ketamir-2 trials.
For accurate information about ketamine-based treatments currently in development, consulting official clinical trial registries such as ClinicalTrials.gov or reaching out to pharmaceutical companies conducting research in this area would be recommended.