Inflammatory Response Research, Inc. (IRR) is a drug development company focused on pharmaceutical products for the treatment of inflammatory disorders and conditions. Our initial product is a combination of levocetirizine (Xyzal®) and montelukast (Singulair®) at specific dosing for the treatment of the common cold as a ‘Behind the Counter’ dose pack. In parallel are the development of injectables for use in traumatic brain injury and acute radiation syndrome..
Products in Development
Marketed commercially as Xyzal® in the United States by Sanofi-Aventis and UCB, levocetirizine is indicated, among other things, for the relief of symptoms associated with seasonal and perennial allergic rhinitis. Levocetirizine is the most effective antihistamine on the market based on safety and efficacy.
Marketed commercially as Singulair® in the United States by Merck, montelukast is approved for the treatment of asthma, exercised induced asthma, and the relief of symptoms of seasonal and perennial allergic rhinitis.
Clinical data to date generated by Dr. May, supported by independent laboratory research, suggests the combination of levocetirizine and montelukast shortens the traditional 7-10 day course of influenza and the common cold by 50%. Both compounds have excellent safety profiles..
The Common Cold
The number of cold treatment eligible patients is expected to grow to about 170 million by 2020 (Mirubi Group 2012). The US market opportunity for the common cold ranges from $1.0 billion to $2.4 billion. Presently there is no FDA approved product that both treats the symptoms and shortens the duration of the common cold.
Traumatic Brain Injury
There is a marked unmet need in this area of medicine with an estimated cost to society of $80 billion / year. Traumatic brain injury (TBI) remains the US military #1 medical unmet need.
Levocetirizine + montelukast can be used in existing treatment paradigms to safely reduce morbidity and mortality in acute brain and lung injury without the side effects associated with steroids. Steroids were removed from the CNS treatment guidelines in 2004 due to an 18% relative increase in two-week mortality. There is currently no safe and effective product to actively treat inflammation following traumatic brain injury.
Acute Radiation Syndrome
Existing therapy for acute radiation syndrome is supportive: IV fluids, prophylactic antibiotics, ACE inhibitors for pulmonary fibrosis, and bone marrow transplantation. Levocetirizine + montelukast as an injectable will allow exposed individuals to tolerate higher doses of radiation while protecting vital organs. The addition to treatment protocols has the potential to benefit millions of people worldwide.
A detailed examination of the pharmacokinetics of levocetirizine at the cell level illuminates the unique anti-inflammatory properties that extend beyond the IgE mediated release of histamine. Most important are its low volume of distribution (0.4 L/kg; ideal drug ≤ 0.6 L/kg), prolonged dissolution time from the H1 receptor in an acidic ph, enhanced receptor affinity as the pure isomer of cetirizine, fastest onset (0.9 hour), fastest to steady state, (approximately 40 hours), and the highest receptor occupancy at 24 hours of any currently available antihistamine. Such parameters impart an anti-inflammatory effect by down regulating the signaling proteins: IL-4, IL-6, and IL-8 as well as cellular adhesion molecules. The latter are a homogeneous group of inducible immunoglobulins, integrins and selectins involved in cell-to-cell adhesion, cellular recruitment, homing and healing.
Levocetirizine has been shown in a laboratory model to decrease ICAM-1, IL-6, IL-8, TLR3 expression and NF-kappa B activation resulting in decreased human rhinovirus (HRV) titers by log-2. Levocetirizine inhibits rhinovirus-induced ICAM-1 and cytokine expression and viral replication in airway epithelial cells. Separate research has shown that many rhinovirus serotypes share the same cellular receptor identifying ICAM-1 as the portal of entry into the cell. Independently, a one-log reduction in viral shedding results in a significant clinical benefit in HRV-infected patients.
Montelukast acts at the CysLT1 receptor to inhibit the physiologic action of leukotriene D4 (LTD4). Leukotrienes are protein mediators of inflammation similar to histamine; however 100-1000x more potent than histamine in the lung. LTD4 is the most potent cysteinyl leukotriene in contracting smooth muscle, thereby producing bronchoconstriction. Moreover, both montelukast and levocetirizine are known to reduce the quantity of eosinophils or their migration to the site of inflammation. An eosinophilic infiltrate is considered a ‘hallmark’ of inflammation.
Acting at multiple points within both the innate and adaptive environments of the immune system, an injectable combination will be ideal as a ‘First Response’ medication for the treatment of traumatic brain injury (TBI) and acute radiation syndrome (ARS). Dose, duration, and delivery are indication specific.