Avonex® (Biogen Idec, MA, USA), a drug indicated for relapsing multiple sclerosis (MS), has reached Japan. It was first launched in 1994 in the USA and later in Europe and it is now serving approximately 130,000 patients in more than 90 countries worldwide.
MS is an autoimmune disorder where the immune system attacks myelin, the insulating sheath covering nerve fibers, resulting in the failure in signal transmission from the brain to other body parts. The onset is usually at 20–50 years of age and the disease is chronic. Patients with MS have various symptoms, including difficulty in movement and loss of vision and hearing.
MS affects more than 1 million people worldwide, 400,000 of whom are from North America. In Japan, approximately 12,000 patients have been diagnosed with MS, with the number of undiagnosed cases believed to be high. Most Japanese patients with acute MS only pursue short courses of treatment and there is a high drop-out rate in long-term therapy owing to side effects and low efficacy.
“MS is a debilitating disease that remains undertreated in Japan and we believe patients can benefit greatly from the availability of a new treatment option,” said Toshio Nakata, President of Biogen Idec Japan. “Anovex is the leading choice for prescribing physicians and their MS patients because it offers efficacy and a convenient dosing regime that patients can adhere to over the long term.”
Anovex is an interferon (IFN)-β1a and is currently the only drug for MS that can be administered once a week. It has proven efficient in slowing down the disease progression and reducing relapse frequency in various clinical trials, with side effects being influenza-like symptoms. Anovex is the most prescribed treatment currently for relapsing MS worldwide and was approved by the Japanese Ministry of Health, Labor and Welfare in July 2006.
“For more than a decade, Biogen Idec has been committed to advancing the treatment of MS and we look forward to extending that dedication to serve patients and their families in Japan,” said James Mullen, Chief Executive Officer of Biogen Idec. “The introduction of Anovex to the Japanese MS community continues our mission of developing important therapeutics to patients around the world.”
Initially, the drug has been introduced to hospitals in Japan and it is expected to become more widely available in the near future.
Source: Biogen Idec, MA, USA (www.biogenidec.com).
Drug combination in rheumatoid arthritis treatment
Genentech Inc. (CA, USA) revealed preliminary positive results of an on-going study of Rituxan® (rituximab) for rheumatoid arthritis (RA) treatment at the Annual Scientific Meeting of the American College of Rheumatology in Washington DC, USA, November 10–15, 2006.
More than 2 million people in the USA are affected by RA. It is an autoimmune disease where the immune system attacks joint tissues, causing damage in cartilage, tendons and bones. Patients with RA suffer from pains and difficulty in movement and can become disabled. RA can also affect other tissues, such as the lungs and eyes.
Although there is no cure for RA, various drugs are available, ranging from pain killers (aspirin) and anti-inflammatory agents (naproxen, ibuprofen) to antirheumatic drugs. These are the first-line treatment and can reduce the symptoms yet they cannot slow down the disease progression.
Recently, a new class of disease-modifying agents has been developed and one of the most prescribed is tumor-necrosis factor (TNF) antagonist. TNF is a protein produced by immune cells in response to infections but, in RA patients, TNF production is unregulated and the resulting excess TNF causes severe inflammation of surrounding tissues. TNF antagonists block TNF activity, hence reducing the symptoms as well as slowing down the disease development.
The study, sponsored by Genentech, involves 155 RA patients who do not respond adequately to TNF antagonist therapy. Patients were given a two-dose course of Rituxan intravenously in combination with methotrexate. The drugs were well tolerated and resulted in significantly higher responses compared with the initial TNF-antagonist therapy. Subsequent use of TNF antagonists following Rituxan also appeared safe, although more data are needed to confirm this.
Rituxan is an antibody that targets and depletes specific RA-associated B cells (CD20+) without affecting other immune cells. The drug was approved by the US FDA for treatment of moderate-to-severe RA in February 2006. Side effects reported following Rituxan treatment include mucosa and skin reactions.
“These preliminary data are encouraging and we will continue to evaluate this patient group to further understand how patients can be treated following Rituxan therapy,” said Mark Genovese of Stanford University Medical Center. Rituxan has also been studied in other autoimmune diseases, such as MS and systemic lupus erythematosus.
Source: Genentech Inc., CA, USA (www.genentech.com).
New option for patients with psoriatic arthritis
The US FDA has expanded its existing approval for Humira® (adalimumab, Abbott IL, USA) as the treatment for psoriatic arthritis (PA). The expanded indication includes inhibiting structural joint damage and improving physical function in PA patients. Humira has also been approved for moderate-to-severe RA and active ankylosing spondylitis (AS).
Similar to RA, PA is an autoimmune disease with RA-like symptoms combined with psoriatic skin symptoms, such as dry, scaly skins with raised, red patches of lesions. If left untreated, PA can be debilitating and disabling. Worldwide, approximately 180 million people suffer from psoriasis, 30% of whom develop PA. It is estimated that 1 million people are affected by PA in the USA alone.
“PA is a multifaceted disease in which patients can experience joint and skin symptoms that may lead to disability and decreased quality of life,” said Abbott’s Vice President Eugene Sun. TNF-α is believed to be a main player in PA pathogenesis as in RA. Humira is a humanized monoclonal antibody that neutralizes TNF-α, hence preventing the disease progression.
The FDA expansion is based on the results of a large randomized, placebo-controlled trial involving 313 PA patients who did not respond well to nonsteroidal anti-inflammatory drugs. Joint damage was reduced significantly following a 24-week treatment and skin lesions also resolved. Daily activities, such as getting dressed, walking and climbing stairs, also became easier to Humira-treated patients compared with placebo-treated controls.
“PA can be debilitating for many people, hindering everyday activities. For these people and others, the new indication for Humira is welcome news to our community,” said Gail Zimmerman, President of the US National Psoriasis Foundation.
Humira has been approved in 67 countries and is used by more than 160,000 patients worldwide with PA, RA or AS. The drug is also being studied in several clinical trials as a potential treatment for other autoimmune diseases.
Source: Abbott Laboratories, IL, USA (www.abbott.com).
β-agonists may worsen inflammation
New findings, published in the December issue of the Journal of Allergy and Clinical Immunology, reveal that β-agonists, a common substance in inhaled drugs for asthma, may actually worsen the disease.
β-agonists, or β-adrenergic receptor ligands, bind to β-adrenergic receptors of smooth-muscle cells, causing these cells to relax. “Inhaled β-agonists are very effective in opening up airways and allowing asthmatics to breathe, but their ability to address the underlying inflammation that causes most asthma has been debated for years,” said Raymond Penn, the lead author of the study.
Asthma is an allergic disease of the respiratory tract that involves cells of the innate immune system, such as mast cells. Upon contact with environmental allergens, such as pollens, or under physical or emotional pressure, mast cells release a large amount of histamine, a substance that causes inflammation in the airways. Various drugs are available for asthmatic patients, yet most of them are only symptom-modifying drugs, such as anti-inflammatory agents (steroids) and bronchodilators (β-agonists).
Using cell-culturing techniques, the researchers have found that β-agonists promote the accumulation of type 2 T cells. As over-reactive type 2 T cells are involved in asthmatic inflammation, the new findings may provide the answer to why asthma tends to worsen over a long course of β-agonist treatment.
“Although further research is needed to confirm that these findings occur in the human body, our research points to an important means by which the immune system is regulated by both therapies and the hormonal system,” said Penn. “From an asthma-management standpoint, these studies further emphasize the need to include anti-inflammatory corticosteroids when treating moderate-to-severe asthma.”
The US FDA has now recommended that a combination of bronchodilators plus anti-inflammatory agents should be used for asthmatic treatment.
Source: Loza MJ, Peters SP, Forster S, Khan IU, Penn RB. β-agonist enhances type 2 T-cell survival and accumulation. J. Allergy Clin. Immunol. doi: 10.1016/j.jaci.2006.09.019 (2006).