MS is a chronic autoimmune disease characterized by the immune system’s attack on specific self-antigens, such as myelin basic protein (MBP) present in the myelin sheath of the central nervous system. This attack on self-antigens leads to the onset of MS, which is characterized by symptoms of numbness, lack of coordination, blindness and paralysis.
Clinical data suggests that Bayhill’s lead product candidate BHT-3009 induces the immune system to tolerize to, rather than attack, the MBP in the myelin sheath. BHT-3009 is a plasmid encoding MBP directed specifically at reprogramming the immune system by modulating the response of the antigen-specific immune cells involved in MS. BHT-3009 is being developed to address Relapsing Remitting MS (RR-MS), which is the most common sub-type of MS. RR-MS is characterized by early stage cycles of disease occurrence followed by complete remission, with relapses appearing every one to two years on average.
According to an article published in The New England Journal of Medicine in 2006, MS is the most common non-traumatic cause of disability in young adults in the United States and Europe. According to the National Multiple Sclerosis Society (NMSS) an estimated 400,000 people in the United States have MS, while more than two million people are afflicted worldwide.
RR-MS affects 85% of MS patients at onset and 55% of the general MS population at any given time. Most RR-MS patients progress to more debilitating disease within 10 to 25 years. While early-stage RR-MS patients tend to remit to a healthy baseline condition, the chronic nature of disease may result in permanent sensory impairment; visual problems; fatigue; impaired coordination, bladder, bowel and sexual dysfunction; and paralysis.
In addition to RR-MS, there are three other diagnoses of MS:
Secondary Progressive (SP) MS: SP-MS begins as RR-MS but slowly worsens into progressive disability that may be associated with superimposed relapses. About 50% of all RR-MS patients progress to SP-MS within 10 years, and 90% within 25 years.
Primary Progressive (PP) MS: PP-MS steadily worsens from the time of onset. While there are no detectable relapses, symptoms may periodically improve slightly or stay the same. PP-MS affects about 10% of MS patients and is most common after the age 40.
Progressive-Relapsing (PR) MS: PR-MS is progressive from disease onset, but with superimposed relapses. As the least common type, PR-MS affects 5% of MS patients.
Current Treatments for MS
Current treatment of MS is threefold, including management of disease progression, relapses, and symptoms. There are currently six therapies approved for use in RR-MS patients in the United States. All of these therapies are non-specific immunomodulatory agents, which reduce the frequency and severity of attacks. Total worldwide 2006 revenue approached $6.0 billion among the drug companies that market FDA-approved RR-MS therapies. Approximately $4.5 billion out of the $6.0 billion total are attributed to sales of interferon beta 1B (Betaseron marketed by Bayer HealthCare Pharmaceuticals Inc.) and interferon beta 1A (sold as Avonex by Biogen Idec Inc.; and as Rebif by EMD Serono, Inc. and Pfizer Inc.). These interferons demonstrate what many consider to be modest efficacy with significant side effects. They also have undesirable administration schedules, ranging from once every other day to once weekly. In addition to interferons, glatiramer acetate (Copaxone marketed by Teva Neuroscience, Inc. and Sanofi-Aventis SA), is a non-specific immunomodulatory agent approved for RR-MS. It accounts for about $1.4 billion in worldwide sales, requires daily injections and demonstrates efficacy that is generally regarded as similar to the interferons.
Due to upredictable efficacy and tolerability associated with current therapies, many MS patients receive multiple therapies over the chronic course of disease. Second-line therapies for RR-MS are recommended for patients who inadequately respond to or cannot tolerate other therapies and include natalizumab (Tysabri sold by Biogen Idec Inc. and Elan Corporation, plc) and mitoxantrone (Novantrone marketed by EMD Serono, Inc.). Tysabri, an immune-modulating drug, is delivered intravenously once every four weeks at a registered infusion facility, but carries a risk of serious and sometimes fatal opportunistic infections. Previously removed from the market due to safety concerns, Tysabri has been re-introduced via a restricted distribution program and label. Novantrone, a chemotherapeutic drug used primarily to treat leukemia, is delivered intravenously four times per year in a controlled medical setting. An association with cardiac toxicity, however, means that patients may only receive a limited lifetime dose of Novantrone.
Currently, there are no approved therapies directed specifically at reprogramming the immune system by modulating the response of antigen-specific immune cells involved in MS. An antigen-specific product that demonstrates efficacy, presents limited side effects and has a superior administration profile could address a severely unmet medical need in MS.
About BHT-3009
BHT-3009 is an antigen-specific plasmid encoding myelin basic protein (MBP) that has the potential to gain a significant share of the multi-billion dollar MS market as an effective treatment with limited side effects and a superior administration profile. Early clinical data suggests that BHT-3009 reprograms the immune system to tolerize to, rather than attack, the MBP in the myelin sheath of the central nervous system of MS patients. In particular, data from two completed placebo-controlled clinical trials signaled this product candidate’s potential to treat RR-MS patients with high levels of immune activity, with a safety profile similar to placebo. In a Phase II clinical trial, BHT-3009 demonstrated a decrease in brain lesions as measured by magnetic resonance imaging (MRI) among a group of patients with high levels of immune activity at enrollment who received the 0.5 mg dose. Results also indicated a tolerizing effect on the immune system as measured by reduction of myelin-specific antibodies in cerebral spinal fluid. In terms of safety, BHT-3009 was well tolerated and patients experienced no significant side effects. Initiation of a Phase IIb clinical trial for in RR-MS is planned for the fourth quarter of 2008.
Clinical trial
