NORMAL BONE

BONE WITH OSTEOPOROSIS

Osteoporosis is a condition in which bone strength and density decreases to a level at which fractures may occur, often with little stress having been placed upon the bone. The most common sites for fractures are the spine, the forearm and the hip. It is estimated that annually in the United States, 700,000 spinal fractures, 250,000 hip fractures and 250,000 wrist fractures occur due to osteoporosis.

Worldwide it is estimated that 200 million people suffer from osteoporosis with an incidence of 8 million fractures per year. Globally one third of all women and one fifth of all men, aged over 50, will have an osteoporotic fracture.

Osteoporosis is most common in the elderly, with up to 70% of people over 80 years of age affected (women four times more commonly than men). Bone loss increases after menopause as levels of oestrogen decline.

Osteoporosis may also occur as a result of illness, such as kidney disease or hyperthyroidism, or, due to treatment with certain medicines such as chemotherapy or steroids. Lack of weight bearing exercise, smoking and low levels of Vitamin D are risk factors for osteoporosis.

Treatment for early or mild osteoporosis is generally with calcium supplements, vitamin D and encouragement to exercise. The main drug treatment is with anti-resorptives (such as bisphosphonates), which reduce bone loss and have been shown to have benefit, particularly on prevention of spinal fractures, if taken for three to five years. However side effects, in particular gastric and esophageal ulcers, eye problems and pain in the muscles and joint, are not uncommon (especially when administered intravenously) and many patients are unable to continue therapy over the longer term, with as many as half of all patients stopping therapy within one year. Post-menopausal women may be treated with oestrogen supplements or with recombinant para-thyroid hormone (PTH), which regulates serum calcium and acts to promote bone growth.

There is a significant clinical need for treatments that can effectively reduce osteoporotic loss of bone strength without producing side-effects that limit treatment exposure and quality of life.

Mesentech’s approach is to use a bisphosphonate in a form that retains its high specificity for bone but which is otherwise blocked from having a pharmacological effect. To this bisphosphonate is attached, via a proprietary linker, EP4a, a drug that stimulates both the growth and quality of new bone. Mesentech’s conjugate product so formed is currently designated as C3. The bisphosphonate remains inactive and acts just as a targeting mechanism to deliver the EP4a directly to the bone. The EP4a is released slowly at the bone where it becomes active and locally stimulates bone growth.  Thus activity is localized at the bone site and not elsewhere in the body, such that side-effects and off-target effects of EP4a, which might otherwise occur, are minimized.

Mesentech’s C3 is a new approach to the treatment of osteoporosis and provides a mechanism whereby bone growth can be stimulated more effectively than with current therapies and in a manner that not only provides improved efficacy but also limits drug exposure and off-target effects thus minimizing side-effects and enabling patients to complete therapy timelines.