Multiple Sclerosis
Overview and Stages
Multiple sclerosis (MS) is a chronic, progressive inflammatory disease that attacks the myelin sheath that surrounds and insulates nerve fibers and facilitates the conduction of nerve impulse transmissions in the central nervous system (brain and spinal cord). In patients with MS, it is believed that activated T-cells (myelin reactive T-cells) infiltrate the central nervous system and trigger the attack on the myelin sheath (called demyelination), while also inducing a damaging general pro-inflammatory immune response. Ultimately, the nerve fiber axons become damaged and cause impulse transmissions to diffuse into the tissue, resulting in the symptoms and disability associated with the disease.

The stages of MS are as follows:

High-Risk Clinically Isolated Syndrome (CIS)
The term "clinically isolated syndrome" (CIS) has been used to describe a first neurologic episode that lasts at least 24 hours. The person has a high risk of a second neurologic event, and therefore, a diagnosis of clinically definite MS within several years.

Relapsing-Remitting Multiple Sclerosis (RRMS)
RRMS is the most common form of MS. Approximately 85 percent of patients are initially diagnosed with RRMS. With RRMS, patients experience relapses during which new symptoms may appear and old symptoms resurface or worsen. Relapses are followed by periods of remission, characterized by full or partial recovery. All currently approved therapies for MS are indicated for the treatment of RRMS.

Secondary-Progressive Multiple Sclerosis (SPMS)
After a number of years many people (approximately 50 percent) who have had relapsing-remitting MS eventually progress to SPMS, a secondary progressive phase of the disease. SPMS is characterized by a gradual worsening of the disease between relapses. In SPMS, relapses merge into a general disease progression and the resulting damage cannot be reversed.

Primary-Progressive Multiple Sclerosis (PPMS)
The most severe stage of MS, PPMS involves a rapid decline in overall neurological function. PPMS does not involve periods of either relapse or improvement. There is presently no cure for PPMS.

Progressive-Relapsing Multiple Sclerosis (PRMS)
People with this type of MS experience a steadily worsening disease from the onset but also have clear acute relapses (attacks or exacerbations), with or without recovery. In contrast to relapsing-remitting MS, the periods between relapses are characterized by continuing disease progression. About five percent of MS patients have PRMS.1

MS affects individual patients in distinctly different ways, highlighting the need for an effective, personalized therapy to treat this disease.

Current MS Treatments
A significant unmet medical need currently exists in connection with the treatment of multiple sclerosis due to the fact that currently available MS treatments possess only modest efficacy and are limited by significant compliance issues related to severe side effect profiles and cumbersome administration approaches/schedules. For example:
  • Currently approved MS therapeutics only address the symptoms of the disease and not its underlying cause(s). As such, these treatments are only able to slow the progression of MS.
  • Many current MS treatments are associated with a number of severe side effects including flu symptoms, headaches and severe injection site reactions. In some cases, these side effects are so severe that patients choose to discontinue their therapy. One particular MS therapy has been linked to virally mediated brain inflammation which has resulted in patient deaths.
  • Treatments that are currently available to patients require administration at least once per month and, in some cases, every day. The frequency of these dosing regimens can place a significant burden on MS patients.
Due to the combination of severe side effects and burdensome treatment schedules outlined above, a significant percentage of patients with MS become non-compliant following two years of treatment.

Ultimately, the limitations of current therapeutic options for MS highlight the need for new safe and effective therapies that treat the underlying cause(s) of MS while offering patients a convenient administration schedule.

The MS Market
It is estimated that MS affects approximately 2.5 million individuals worldwide, with two-thirds of those being women. There are approximately 400,000 patients in the U.S. that suffer from MS.1 In 2006, the global sales of MS therapeutics were estimated at approximately $6 billion with the U.S. accounting for roughly 50 percent of those sales.2

MS remains a challenging autoimmune disease to treat because the pathophysiologic mechanisms are diverse, and the chronic, unpredictable course of the disease makes it difficult to determine whether the favorable effects of short-term treatment will be sustained. Some experts believe therapies that are easy to use and can safely prevent or stop the progression of disease are best positioned to meet the greatest need in MS.

1 National Multiple Sclerosis Society. Just the Facts 2006-2007. Washington, D.C.: National Multiple Sclerosis Society, 2007.
2 Datamonitor. Commercial Insight: Multiple Sclerosis. Datamonitor, 2007.