MIRA Pharmaceuticals has announced that its oral ketamine analog, Ketamir-2, has outperformed current FDA-approved neuropathic pain treatments in preclinical studies. In trials using a nerve ligation model, Ketamir-2 demonstrated 112% more effectiveness than pregabalin and 70% greater relief than gabapentin by Day 22, with significant pain relief appearing as early as Day 15.
The studies, conducted in female rats, built upon earlier successful trials in male subjects where Ketamir-2 fully reversed neuropathic pain while oral ketamine showed no effect. MIRA plans to submit an Investigational New Drug (IND) application by the end of 2024, with Phase 1 clinical trials slated for Q1 2025. The company holds exclusive rights for Ketamir-2 in the U.S., Canada, and Mexico.
It’s been something of a long, strange trip for ketamine, the Schedule III dissociative anesthetic that is also used as an animal tranquilizer. In the pandemic, demand for the drug as an off-label depression and anxiolytic agent surged, with some companies billing it as a ‘psychedelic’ therapy given its ability to induce hallucinations, ultimately leading to an FDA warning regarding the practice. Toward the end of 2023, acute effects of ketamine played a role in Friend’s star Matthew Perry’s death.
A ketamine pivot
Against this backdrop, MIRA’s approach with Ketamir-2 represents something of a pivot. Rather than repurposing ketamine itself, the company has developed a novel patent-pending analog specifically designed to target neuropathic pain pathways. The therapy also potentially avoids the dissociative effects and abuse potential that have complicated ketamine’s medical use.
Racemic ketamine as well as its stereoisomers, S-ketamine (esketamine) and R-ketamine (arketamine), have dissociative properties, with the former being more potent. Traditional ketamine is also poorly absorbed through oral administration, making infusions or, in the case of Spravato, nasal delivery, the norm.
The neuropathic pain market, currently dominated by gabapentin and pregabalin, itself faces growing scrutiny over side effects and dependency issues. Two mainstays of treatment, gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica), can have significant side effects in some patients, ranging from dizziness to nausea and weight gain in some. Gabapentin has been linked with aggressive behavior in some cases, while pregabalin may cause muscle pain or weakness. Both medications can potentially lead to withdrawal symptoms.
Sales of the therapies remain strong. Precedence Research projects gabapentin sales to hit $4.95 billion by 2033, growing at a 6.12% CAGR. Meanwhile, Allied Market Research estimates that pregabalin sales could reach $2.2 billion by 2032.
Expanded development plans
MIRA is pursuing multiple development paths for Ketamir-2. Among them are ongoing studies in chemotherapy-induced neuropathy that could qualify for FDA breakthrough designation. It is also exploring additional research in diabetic neuropathy and pursuing government grants for PTSD and other neuropsychiatric conditions. It is also preparing scientific publications to share findings with the medical community.MIRA notes that the DEA has determined that Ketamir-2 would not be classified as a controlled substance, potentially streamlining the path to market. Beyond neuropathic pain, MIRA is also developing MIRA-55, a novel pharmaceutical marijuana analog, for anxiety and cognitive decline associated with early-stage dementia.
Filed Under: Neurological Disease
