Samumed Begins Phase 3 Trial for Knee Osteoarthritis

San Diego-based biotechnology company Samumed has recently announced that it will be moving to phase 3 clinical trials of its drug lorecivivint (SM04690) for the treatment of knee osteoarthritis.

What is osteoarthritis?

Osteoarthritis is the most common form of arthritis in the knee and a leading cause of adult disability, particularly among older people. This degenerative, “wear-and-tear” arthritis is characterized by the destruction of the articular cartilage and structural changes to the bone, which leads to pain, inflammation, and loss of joint function and mobility. It occurs most often in people who are at least 50 years old, but it may occur in younger people as well.

During the progression of osteoarthritis, the cartilage in the knee joint steadily wears away and becomes frayed and rough, and the protective space between the bones decreases in size. This results in bone grinding on bone, which can create painful bone spurs.

Some estimates suggest that there are around 30 million adults suffering from osteoarthritis, the majority of which is due to aging. The condition robs people of their quality of life and independence while harming workplace productivity and increasing healthcare costs. The current treatment options for patients are very limited in nature, as no approved disease-modifying therapies are available at this time.

Moving to Phase 3

This phase 3 trial, known as STRIDES (SM04690 Trial Evaluating a Randomized Injection for Determination of Efficacy and Safety), will evaluate the ability of lorecivivint to ease the symptoms of knee osteoarthritis, with a focus on patient outcomes and the modification of disease progression.

In the previous phase 2 trial, lorecivivint demonstrated a reduction in pain along with improvement of function and medial joint space width, a marker of disease progression, in patients with knee osteoarthritis. The data was promising and was enough to encourage the launch of this phase 3 trial.

We recently completed the investigator meeting for STRIDES X-ray and anticipate enrolling our first subjects in the near future. Initiating this trial represents a major milestone for lorecivivint, Samumed, and potentially for the millions of patients with OA of the knee. We look forward to providing further updates on this study, as well as the additional STRIDES trials, throughout 2019.

– Yusuf Yazici, M.D., Chief Medical Officer of Samumed

What is Lorecivivint?

Lorecivivint (SM04690) is a small-molecule inhibitor of the Wnt pathway, which regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning, and organogenesis during embryonic development.

Samumed is focused on the part of the Wnt pathway that regulates the self-renewal and differentiation of adult stem cells and is critical for tissue maintenance and organ health. Wnt is an important signaling pathway that controls when stem cells differentiate and thus supports the formation, replenishment, and repair of all bodily tissues.

The problems start when the Wnt pathway becomes dysfunctional and its carefully regulated balance fails, which leads to poor tissue upkeep and repair and, most often, the onset of disease in a particular tissue or organ. Lorecivivint targets the Wnt pathway in order to reset the balance and restore normal function so that healthy tissue maintenance can resume once again.

The company claims that its preclinical data suggests that lorecivivint affects joint health in three key ways: generation of new cartilage material, slowing of cartilage loss, and a reduction of inflammation.

Conclusion

There are currently no approved effective therapies for osteoarthritis that modify disease progression, so a successful drug could improve the quality of life of many older people who suffer from this age-related disease.

As to whether the Wnt pathway is the optimal approach, that is another question; it is likely that a full repair approach, such as one proposed by the Hallmarks of Aging or the SENS Research Foundation, may ultimately prove more effective; however, until such technologies are available, drugs such as lorecivivint at least represent a near-future stopgap, assuming that phase 3 goes well. If it does, then approval may not be far away.