SynviscOne

Osteoarthritis (OA) knee pain is one of the common ailments one can face as either weight is gained, joints are damaged, or as one naturally ages. [1] In healthy knees, synovial fluid cushions the joint to provide flexible, pain free movement. However, as one ages, the fluid can break down and degrade causing a decrease in the amount of cushioning on the knee. As an attempt to alleviate the pain induced by OA as a result of the degraded synovial fluid the Synvisc-One was created as a natural substance that acts to both lubricate and cushion the knee joint much like the synovial fluid would naturally.[2]

=What is Osteoarthritis? =

Osteoarthritis (OA) is known as the “wear-and-tear” kind of arthritis and is a chronic condition characterized by the breakdown of the joint’s cartilage. Cartilage is the part of the joint that cushions the ends of the bones and allows easy movement of joints. As the cartilage breaks down, which in the case of OA is synovial fluid, the bones rub against each other, causing stiffness, pain and loss of movement in the joint. However, even with the degrading of the cartilage, OA does not instantaneously set on but rather develops in several different stages. As previously mentioned, cartilage loss leads initially to loss of elasticity in the join thus making the joint easier to damage and ultimately use.

In turn the loss of cartilage also induces changes to underlying bone causing it to thicken or bony growths, called spurs to develop near the end of the bone at the affected joint. The spurs may become loose during movement allowing them to freely float within the joint space and induce inflammation. Cytokines in the joint lining can also add to the inflammation as enzymes further damage the synovium. Ultimately all of these changes induce the final disease of OA causing the shape and makeup of the joint to be altered in a way that prevents it from properly operating. [3]



A knee affected by osteoarthritis

(A) Cartilage that has worn away

(B) Bone spurs may develop

(C) Break down of joint fluid

Image Citation

=Causes of Osteoarthritis=

Despite the research conducted, there is no known cause of osteoarthritis (OA), however several risk factors have been identified as being components likely to induce the disease. One risk factor for the development of OA is age. As once ages the more the joints have been utilized as thus the “wear and tear” effect ensues. Another risk factor is obesity provided increased body weight is particularly felt on ones knees since they carry the brunt of weight. It has been shown that on average for every pound gained, three pounds of pressure is added to the knees causing the cartilage to degrade quicker. Yet another cause of OA development is injury to the joint or over use of the joint during repetitive movements. Genetics and heredity also can influence the development of OA. Inherited abnormalities of the bones that affect the shape or stability of the joints can lead to OA provided the abnormalities can prevent the joints from fitting together smoothly. Lastly, muscle weakness can be a risk factor in development of OA. Although several risk factors have been indentified it is important to note that none of them are a direct cause of OA, but rather in combination the factors can lead to a higher risk of developing the ailment. [3]

=Symptoms of Osteoarthritis and How is it Diagnosed=

Some of the most common symptoms identified by those who suffer from osteoarthritis include soreness and stiffness of joints after overuse or inactivity such as when one sleeps. Pain can be felt as well in the joints by the weakening of muscles surrounding the joint. More drastic side effects may include deterioration of coordination, posture and walking due to pain and stiffness. In particular to osteoarthritis of the knees, one may experience pain, grating when moving the knee, and weakening of large thigh muscles. A medical professional can diagnose the disease by analysis of ones medical history along with a variety of other procedures. One medical screening technique that could be used is x-rays that can view loss of joint cartilage, narrowing of the joint space between adjacent bones, and bone spur formation. Arthrocentesis can also be used during which a sterile needle is used to remove joint fluid for analysis. Joint fluid analysis is useful in excluding gout, infection, and other causes of arthritis. Lastly, arthroscopies can be done which are surgical techniques in which a viewing tube is inserted into the joint space. Abnormalities of and damage to the cartilage and ligaments can be detected and sometimes repaired. [3]

=How Synvisc-One Helps Osteoarthritis=

Synvisc-One is prescribed after patients suffering from osteoarthritis have not responded to typical conservative or non-pharmacological pain management techniques such as acetaminophen. This product is only for use in the synovial knee joint and has not been tested or approved for other joints in the human body. Synvisc-One works by mimicking healthy synovial fluid in the joint to help relieve pain caused by the effects of osteoarthritis in the knee joint. [2]



A knee injected with Synvisc-One

(D) Synvisc-One injected in knee

Image Citation Synvisc-One is comprised of two different polymers made of hylan. This polymer was developed from hyaluronan of chicken combs of birds from the United States as well as Canada. When this hyaluronan substance is chemically cross-linked, hylans are formed. [4] Synvisc-One (which replaced the original SYNVISC) has two different hylans in the injection. Hylan A is a fluid and, by volume, comprises 80% of Synvisc-One while the other 20% of the volume consists of Hylan B which is a gel. Because of this composition, Synvisc-One is considered hylan G-F 20. This composition makes this injection almost identical to human synovial fluid, both in molecular weight and viscoelasticity. [4]



The Synvisc-One hylan polymer

Image Citation

=Genzyme - About the Company=

The corporation that was responsible for researching, developing and manufacturing SynviscOne to treat OA was the Genzyme Corporation. Genzyme is one of the world’s leading biotechnical companies, employing over 12,000 people worldwide and grossing around $4.5 billion annually. They are dedicated to reaching as many patients as possible, specifically focusing on patients with rare inherited disorders, kidney disease, orthopedics, cancer, transplant and immune disease, and cardiovascular disease. Based on their 2008 statistics, SynvicOne came in 4th place with approximately $263 million in revenue. [5]

Genzyme is not only committed to developing new treatments for people in the United States, but they are driven to improve the lives of people around the world. Genzyme is a global corporation consisting of 85 locations in over 40 countries, including 17 manufacturing facilities and 9 genetic testing laboratories; the company's products are available in nearly 100 countries. In 2005, Genzyme was chosen to receive the National Medal of Technology, the highest honor awarded by the President of the United States for technological innovation. [5]

Clinical study: Conducted on 253 patients in 6 countries outside the United States. Patients were at least 40 years old, had mild or moderate knee OA and were experiencing moderate to severe pain. Patients in the study were given either:

1. A single injection of Synvisc-One

2. A "saline control

Goal: To determine how well Synvisc-One reduced knee pain during five common activities (walking, going up stairs, etc.). Doctors evaluated the patients at weeks 1, 4, 8, 12, 18 and 26.

Results: The study showed that patients who received Synvisc-One had significantly less pain over six months and felt significantly better than the control group. Specifically, 71% of patients reported pain relief with Synvisc-One. Most patients reported pain relief starting at week four. [6][7][8]

In 2008, Synvisc sales were at $263 million while in the next year, 2009, they increased 25% to $329 million in sales. However, when Synvisc-One was approved in the U.S. in 2009, the sales exceeded those of Synvisc by 25%. [9] The release of SynviscOne to the market greatly increased the corporation’s revenue. Most of the funds that aided in funding the research and development of the product came from the corporation’s revenue. In 2008 alone, the corporation recorded annual revenue of $4.6 billion with an increase of 21% since 2007. Furthermore, they generated a total of $1.5 billion dollars in cash revenue, which would further add to research funding. [5]

=Translation of the Basic Research on SynviscOne into a Marketable Product=

Although no current research is being conducted to further develop SynviscOne provided it is open to the market for sale, a great deal of clinical trials had to be done first to ensure the safety and efficacy of the product. Not a lot of information is provided on how the product was initially developed however; the progress of clinical trials prior to its release is well document. The first trial of the efficacy of Synvisc came in April 2004 and was completed in February 2006. The study was entitled “A Study of the Safety and Efficacy of Synvisc in Patients With Symptomatic Shoulder Osteoarthritis” and the purpose of the study was sited as being to evaluate the safety and efficacy of Synvisc in patients with symptomatic shoulder osteoarthritis (OA). To conduct the study, patients were given Synvisc; with the possible administration of a second injection where insufficient symptomatic pain relief was experienced during the 3 month follow up period. In order to be in the study candidates had to be at least eighteen, and suffer symptomatic OA pain of shoulder. The study was also complete in France, and Germany along with the United States. After the study was complete the product was determined to be safe and effective so clinical trials progressed to other parts of the body. [5]

The next clinical trail was entitled “A Study of the Safety and Efficacy of Synvisc in Patients With Symptomatic Ankle Osteoarthritis”. The study was initiated in November 2003 with the aim of evaluating the safety and efficacy of Synvisc in patients with symptomatic ankle osteoarthritis (OA). In the study the volunteers were dosed with Synvisc until the completion date of February 2006. Much like before those in the study were required to be at least eighteen years old and suffer symptomatic OA pain of ankle. Furthermore, the study was also completed much like the first in various counties including Italy, Germany, the United States and the Netherlands. Along with the clinical trial focusing on the efficacy of Synvisc on those suffering OA of the ankle and shoulder, a study entitled “A Study of the Safety and Efficacy of Synvisc and Depo-Medrol in Patients With Osteoarthritis of the Hip” was initiated in November 2003 to study the safety and efficacy of Synvisc and Depo-Medrol in treating patients with osteoarthritis (OA) of the hip. The study was conducted in research labs in twenty-five states ranging form New York to Arizona. In April 2003 the study concluded demonstrating that the product was successful in treating hip OA pain. [5]

The last clinical study conducted is the one that is most applicable to the focus of this project, which was the treatment on OA in the knee via SynviscOne. The study was entitled “A Study of the Safety and Efficacy of Synvisc in Patients With Symptomatic Osteoarthritis of the Knee” and was initiated in May 2005. The aim of the study was to evaluate the safety and efficacy of Synvisc in patients with symptomatic knee osteoarthritis (OA). In the study those being evaluated were dosed with Synvisc, with a possible repeat treatment with Synvisc after the week 26 visit. In order to be eligible for the study individuals had to be of 40 Years and above who suffer OA in their knee. Like all the other studies, individuals in a variety of countries were evaluated including the Czech Republic, Belgium, France, Germany, Netherlands, United Kingdom, and the United States. In August 2006 the study was completed showing the efficacy and safety of Synvisc treating OA in the knee. Thus the product was released entitled SynviscOne for OA knee pain. [5] As can be seen the translation of the initial product went through a series of four clinical trials fixating on four varying parts of the body that could suffer from OA.

=Success of SynviscOne=

The product is currently considered to be a great success since its release. It was been approved by the European Union, along with the Asian and Latin American nations. The FDA has also supported the release of SynviscOne and approved it as the only single-injection viscosupplement approved for the treatment of OA knee pain in the United States. SynviscOne has the potential to possibly redefine the market for viscosupplementation products. It offers the chance to extend the benefits of therapeutic treatments to a wider spectrum of individuals provided the treatment is both less expensive and does not come with the burden of multiple injections. Thus SynviscOne is currently both a very successful and unchallenged product for the treatment of OA pain. [5]

=Market Potential=

With technology expanding more and more into our healthcare system, Americans are living longer but not necessarily pain free. The life expectancy of Americans increased from 69 years in 1960 to 78 years in 2010. There are certain benefits that come with an extra 10 years of life, such as finishing the bucket-list, however, the health problems that accompany old age may outweigh most those benefits. According to a 2004 statistic by the CDC, 50% of people aged 65+ report they have some form of arthritis while 27 million people specifically have osteoarthritis. [10]

The baby boomers are also earning the right to be called a “senior citizen.” And as they steadily grow older, they bring with them a boom of arthritis. Synvisc-One will be able to target this group. Synvisc-One is the only nonsystemic therapy delivering up to six months of pain relief with just one injection. The ideal candidate for this type of treatment will be people with mild to moderate OA of the knee, people with comorbid conditions who should avoid the risks of NSAIDs and Celebrex®, and people with busy schedules who need the simplicity of a single injection.

There are also other treatments on the market that are able to provide pain relief for mild to moderate OA. Euflexxa® is also a direct injection of hyaluronan into the knee joint. [11] However, Euflexxa requires 3 injections; one a week for 3 weeks, Synvisc-One only requires 1 injection. ORTHOVISC® is the only treatment made from ultra-pure natural hyaluronan, which is found in healthy joint fluid, and also provides up to 6 months of relief. [12] But once again, it requires 1 injection for 3 consecutive weeks. Overall, Synvisc-One provides the same relief with only one injection.

Patients who have discomfort in their knees need to consult with their doctor local or other qualified health care provider. However, it should be noted that though physician may administer Synvisc-One, they may not have received training from the Genzyme Corporation and they cannot guarantee the physician will provide you with Synvisc-One therapy.

=Bibliography=

[1] "MedlinePlus." Osteoarthritis. .

[2] 2010. Synvisc One. .

[3] "Arthritis Foundation." 2010. Osteoarthritis. .

[4]"MedlinePlus." Osteoarthritis. .

[5] http://www.genzyme.com/

[6] http://www.synviscone.com/about/medical-study.aspx

[7] http://www.synviscone.com/~/media/Files/SynviscOne/synvisc-one-patient-information.pdf

[8] http://www.genzyme.com/research/patents/literature_orthopaedics.asp - Primary Literature of clinical studies

[9]http://www.businesswire.com/portal/site/genzyme/index.jsp?ndmViewId=news_view&ndmConfigId=1019673&newsId=20100112006676&newsLang=en

[10] http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm

[11] http://www.euflexxa.com

[12] http://www.orthovisc.com/