Multiple Sclerosis

Symptoms and Stages
The National Multiple Sclerosis Society describes MS as "an unpredictable, chronic disease of the central nervous system (the brain and spinal cord) in which inflammation and breakdown in the protective insulation (myelin sheath) surrounding the nerve fibers of the central nervous system occurs." Multiple sclerosis is considered to be an autoimmune disease characterized by the inflammatory demyelination of neurons in the central nervous system (CNS). Autoimmunity is when the body's natural defenses (the immune system) mistakenly attack the body's own tissue. "Auto" is derived from the Greek auto, meaning self and autoimmune means attacking self.

Although the exact pathogenesis of the disease is unknown, it is believed that the clinical manifestations of multiple sclerosis are the result of an immune reaction consisting of the penetration of the blood-brain barrier (BBB), entrance into the CNS, and recognition of the myelin basic protein (MBP), proteolipid (PLP) and myelin oligodendrocyte glycoprotein (MOG) as foreign. The immune system's attack on these proteins induces the stripping of the protective coating of myelin and the eventual formation of plaques. These plaques or lesions can be found throughout the central nervous system, but are most prominently found in the white matter, optic nerve, brainstem, spinal cord, and cerebellum. The formation of these plaques causes the conduction of action potentials along the axon to be reduced, resulting in neurocognitive or neuromuscular impairment. Clinical symptoms of multiple sclerosis include: optic nerve dysfunction, internuclear ophthalmoplegia, upper motor neuron weakness, tremors, ataxia, sensory disturbances, and autonomic dysfunction (Bansil). While the typical clinical course of multiple sclerosis is characterized by relapsing and progressive disability, there have been examples of subclinical cases of MS where the diagnosis is confirmed only by the presence of large confluent, demyelinating plaques found only upon autopsy.

Twice as many women as men suffer from this disease with the onset of symptoms generally occurring between the ages of 20 and 50. MS is not considered terminal, as the projected life span for most MS patients is 93% of that of the non-MS affected population. However that are documented deaths due to MS and in 2000 there were 2,480 adult deaths (mortality among adults =25 years old) due to MS.

In 1996, MS was formally classified into four phases or presentation categories (National MS Society):

This is the most common phase of MS at time of diagnosis, affecting approximately 70% of MS patients - This group experiences clearly defined flare-ups (relapses), followed by partial or complete remissions between attacks that are free of disease progression.

Affecting approximately 15% of MS patients, this group experiences a nearly continuous worsening of their disease from the onset with no relapses or remissions.

Fifty percent of the relapsing-remitting patients eventually develop this form of the disease within 10 years of diagnosis. This phase is characterized by an initial period of relapsing-remitting disease followed by steady worsening with or without flares or minor remissions.

Affecting approximately 15% of MS patients, this group experiences a steady worsening of the disease from the onset but also have relapses with or without recovery. This stage is different from the relapsing-remitting stage because the periods between relapses are characterized by continuous disease progression. It is important to note these four categories of MS since pharmaceutical products may be indicated for only one of these specific categories.

Current Treatments
Products marketed in the United States for treatment of MS address only the symptoms of the disease. These products produce limited benefits to MS patients ranging from decreases in rate of relapse, to decreases in development of new lesions to delays in progression of disability. They generally reduce the number of relapses of MS patients experience by approximately one- to two thirds.

It usually takes six to nine months for current MS drugs to be clinically effective. These drugs are cumbersome to administer and cause unpleasant side effects in many patients. In addition, a large number of MS patients cannot tolerate beta interferon treatments, which are the leading products for MS treatment. Current therapies are very expensive with patient costs for all of the approved drugs in the range of $17,000 to $23,500 per year. Additional expenses are incurred by the patient to treat associated symptoms of MS, such as bowel or bladder inflammations, impaired vision, vertigo, depression and even paralysis.

Opexa Therapeutics Technologies
We have developed a novel therapeutic vaccine, Tovaxin TM , consisting of modified autologous myelin-reactive T cells. This vaccine induces an immune response directed against T cells within the patients that are self-reactive with myelin. Immunization with Tovaxin TM can greatly reduce the number of these autoreactive cells in MS patients and thus may attack the underlying cause of MS.

We have also identified unique T cell receptor sequences found in autoreactive T cells in MS patents, which has led to preclinical development of peptide-based vaccines. Two patents have been filed relating to this technology.

The Multiple Sclerosis Market
More than 400,000 Americans and more than 2.5 million people around the world suffer from MS. Approximately 10,000 new cases develop each year in the United States. The National Institute of Neurological Disorders and Stroke estimates that the total financial burden of this disease in economical, social and medical costs exceeds $2.5 billion in the United States each year.

Although no cure for the disease exists, current therapeutics, such as Biogen Idecs Avonex and Teva Pharmaceuticals Copaxone slow down the permanent degeneration of neural tissue. These drugs, along with Schering AGs Betaseron and Serono SAs Rebif, form the class of therapeutics known as disease modifying drugs (DMDs) and comprise over 95% of the over $3.5 billion multiple sclerosis therapeutics market. The dynamics of this market will dramatically change in 2005 with the entrance of Biogen Idec and Elans Tysabri (formerly known as Antegren), which will shift market share distribution within the DMD class. In a survey of 53 neurologists and five reimbursement specialists, Navigant Consulting found that Tysabri will drastically affect the prescribing trends of physicians treating multiple sclerosis. Nearly half of neurologists surveyed expect to prescribe Tysabri as a first line treatment to their patients, and to switch at least 30% of their patients currently taking the other DMDs to Tysabri. By 2009, five other emerging compounds currently in late-stage Phase II or later are expected to launched, but only Sanofi-Aventis HMR-1726, which offers an oral formulation, will have an impact on the market.

The top-selling disease modifying drugs (DMDs) currently marketed for MS are estimated to generate approximately $4 to 6 billion in sales. These DMD products are all injectables and require daily to once a month administration.