Breakthrough Clinical Results
Oragenics, Inc. has partnered with Sterling Pharma Solutions for the Good Manufacturing Practice (GMP) production of ONP-002, its lead drug candidate for treating concussion. This agreement secures domestic production capabilities to support upcoming Phase IIb clinical trials, expected to begin next year. The collaboration is a significant milestone for Oragenics, enabling the company to advance its clinical development strategy for a condition currently lacking FDA-approved pharmacological therapies. Sterling's expertise in CNS therapies and ability to meet tight deadlines will be crucial in bringing ONP-002 to market.
Key Highlights
- Manufacturing agreement with Sterling Pharma Solutions for ONP-002 production.
- Secures U.S.-based GMP manufacturing for Phase IIb clinical trials.
- Supports Oragenics' clinical development strategy for concussion treatment.
- Addresses the lack of FDA-approved pharmacological therapies for concussion.
Incidence and Prevalence
Global Incidence and Prevalence of Concussion
The global burden of concussion and traumatic brain injury (TBI) represents a significant public health challenge, with varying estimates across different populations and research methodologies.
Global Incidence
According to recent data, the incidence of mild traumatic brain injury (mTBI) is estimated at 200-300 per 100,000 persons annually for hospitalized patients, and likely twice as high when including non-hospitalized cases. Some population-based studies have reported substantially higher rates exceeding 700 per 100,000. Globally, an estimated 10 million people are affected by TBI annually.
The World Health Organization projects that traumatic brain injury will surpass many diseases as the major cause of death and disability by 2020, highlighting its growing significance as a global health concern.
Regional Variations
Significant regional disparities exist in TBI incidence:
- Latin America and Sub-Saharan Africa show higher TBI-related incidence rates of 150-170 per 100,000, compared to the global rate of 106 per 100,000, primarily due to road traffic injuries (RTIs).
- In high-income countries, a changing epidemiological pattern shows decreasing road accident injuries among young adults, while the proportion of falls has increased with population aging.
Sport-Related Concussions
In specific populations, such as sparring taekwondo athletes aged 12-16 years, research found incidence rates of head kicks and concussions at 133.5 and 41.4 per 1000 athlete-exposures, respectively.
A 2015 New Zealand study identified 291 sports-related traumatic brain injuries (21% of all TBIs), equating to an incidence rate of 170 per 100,000 in the general population.
Demographics and Causes
In a 2014 Pakistani study, the most commonly affected age group was 21 to 30 years (34.1%) with a male to female ratio of 3.3:1. Injuries were predominantly caused by road traffic accidents (62.6%), followed by falls (31.7%) and assaults (5.5%).
Research Limitations
The prevalence estimates vary widely according to case definitions and studied populations. Under-reporting and varying definitions of concussion make it difficult to estimate the true prevalence. The majority of concussion/mTBI research comes from Canada and the United States, with global perspectives on management and prognosis lacking, particularly in low and middle-income countries.
There remains a significant gap in data regarding incidence, risk factors, sequelae, financial costs, and social impact of TBI globally. Most TBI incidence studies have focused on hospital-based samples, and there are no established criteria for designing high-quality epidemiological studies.
The 2020 National Health Interview Survey (NHIS) has begun including questions on concussion symptoms and diagnosis to provide a more complete understanding of the public health burden, acknowledging that children with mild injuries may not receive medical attention or diagnosis.
Mechanism of Action
Three Most Common Mechanisms of Action in Trials for Unapproved Concussion Drugs
Glutamate Receptor Antagonism
The first common mechanism involves targeting glutamate receptors. Glutamate receptor antagonists are considered among the most promising therapeutic approaches for traumatic brain injury (TBI), including concussions. These compounds aim to interrupt the pathophysiological mechanisms that lead to secondary brain injury. By blocking excessive glutamate activity, these agents may help prevent the excitotoxicity that occurs following head trauma, potentially limiting neuronal damage in the acute phase after concussion.
Calcium Channel Antagonism
The second common mechanism focuses on calcium channel antagonists. These compounds are designed to prevent calcium influx that contributes to neuronal damage following TBI. Excessive calcium entry into neurons after concussion triggers various destructive cellular processes. Calcium channel antagonists are being investigated in clinical trials as a promising approach to mitigate this aspect of the injury cascade, potentially preserving neuronal integrity and function after concussive events.
Free Radical Scavenging
The third common mechanism utilizes free radical scavengers. These compounds target oxidative stress and the production of reactive oxygen species that occur after brain injury. Following concussion, there is a significant increase in free radical production that can damage cellular components including membranes, proteins, and DNA. Free radical scavengers are considered among the most promising therapeutic approaches for TBI treatment as they may help neutralize these harmful molecules and reduce secondary damage.
Despite these promising mechanisms, it's important to note that "no drug has achieved this goal so far" of effectively treating TBI or concussion. The development of effective treatments is complicated by the blood-brain barrier (BBB), which excludes approximately 100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs from reaching the brain.
Future approaches may involve combination therapies that utilize several pharmacological agents together, possibly with other treatment modalities such as mild hypothermia, tailored to specific patient subgroups. Recent research has also explored compounds like Remazolam which affects astrocytes to improve TBI outcomes via regulating Cx43, demonstrating potential for protecting neurological function.
Other notable mechanisms being investigated include cyclosporin A for ameliorating secondary damage and various anti-inflammatory drugs, though studies show mixed results with some anti-inflammatory approaches potentially worsening TBI pathology.
Drug used in other indications
ONP-002 Clinical Trials Beyond Concussion
Based on the available information, I cannot provide details about additional indications for ONP-002 beyond traumatic brain injury/concussion. The context explicitly states that none of the provided input materials contain information about ONP-002 as a pharmaceutical agent.
The context indicates that while various treatments and studies related to traumatic brain injury were discussed in the source materials, including:
- N-methyl D-aspartate antagonists
- Dabigatran
- Cerebrolysin combined with repetitive transcranial magnetic stimulation (rTMS)
- AST-004 (an adenosine A1/A3 receptor agonist)
However, none of these discussions included specific information about ONP-002, its clinical trials, or intervention models for indications beyond concussion.
Without specific information about ONP-002's additional clinical trials or intervention models in the provided context, I cannot detail which other indications this pharmaceutical agent is being evaluated for beyond traumatic brain injury/concussion.