The chronic pain associated with OA, in particular the severe pain experienced by nearly a quarter of OA sufferers, is one of the most common reasons for chronic opioid prescriptions. Additionally, OA is the highest cause of work loss in the United States.
In individuals with OA, protective cartilage on the ends of the bones gradually deteriorate, and the bones around the joints harden and form edges. These changes cause pain, swelling and difficulties moving the joint. OA can affect any joint, but it occurs most often in knees, hips, lower back and neck, small joints of the fingers and the bases of the thumb and big toe. OA also results in bony changes of the joints, such as bone spurs, deterioration of tendons and ligaments, and various degrees of joint inflammation. OA can cause pain severe enough that patients experience difficulty with simple daily movements such as walking, climbing stairs or even rising from a chair.
There is no cure for OA. As a result, current treatments are intended to address symptoms (in particular relief of pain and improvement in functional status) and with exercise that maintains muscle mass and supports the knee. Despite these currently-available therapies, many patients still suffer with chronic moderate-to-severe OA pain. When the patient can no longer tolerate the pain and disability, a surgical procedure can be performed which replaces the natural joint with an artificial joint.
Knee OA is the most common form of OA. It is estimated that approximately 18 million people in the United States are diagnosed with knee OA, and that number is expected to grow to in excess of 30 million by 2030.
In the case of the knee joint, as OA progresses the structure of the knee changes as cartilage erodes exposing bone and nerve fibers. The joint becomes inflamed and the lack of cartilage leads to stiffness and deterioration of movement and flexibility. Patients experience inflammatory pain and discomfort moving the joint. The pain is often severe, which can be debilitating and prevent people from carrying out daily activities.
Centrexion Therapeutics’ most advanced product candidate, CNTX-4975, is a synthetic, ultra-pure intra-articularly injected preparation of trans-capsaicin, intended for the treatment of moderate-to-severe pain associated with knee OA. CNTX-4975 has demonstrated significant pain relief and a favorable tolerability profile in a Phase 2b clinical trial in patients with moderate-to-severe pain due to knee OA.
In this trial, treatment with a single intra-articular injection of CNTX-4975 resulted in one of the largest reductions of pain associated with knee OA reported in any placebo controlled clinical trial. In the first quarter of 2018, we began enrolling subjects in the first of two Phase 3 registration trials for CNTX-4975. In the second half of 2018, we began enrolling subjects in OA-303, an open label safety trial with approximately 850 subjects, and in VICTORY-2, the second pivotal Phase 3 registration trial for CNTX-4975 that includes repeat dosing. In January 2018, CNTX-4975 was granted Fast Track Designation by the U.S. Food and Drug Administration for the treatment of pain associated with knee OA.
1 Hootman JM, Helmick CG. Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum. 2006;54:226–9.