Yusuf Yazici, MD, chief medical officer of Samumed, discusses SM04690(Lorecivivint) at ACR 2019.
Results of a study presented at the 2019 American College of Rheumatology annual meeting in Atlanta, GA, are suggesting a novel small molecule could be an effective disease-modifying treatment for osteoarthritis.
SM04690, also known as lorecivivint, uses a novel mechanism of Wnt pathway inhibition, chondrocyte differentiation, and anti-inflammation and data examining its use in phase 2 studies was presented at ACR 2019 demonstrated its ability to improve pain and function out to 12 months in most patients.
For a greater understanding of these studies and the potential for lorecivivint as a treatment for knee osteoarthritis, MD Magazine sat down with Yusuf Yazici, MD, assistant professor at NYU Langone and chief medical officer at Samumed, the developer of lorecivivint.
MD Mag: Can you describe lorecivivint and ongoing trials examining its use for knee osteoarthritis?
Yazici: So, lorecivivint is the small molecule drug that we're developing for the treatment of knee osteoarthritis as a disease-modifying drug. There's an unmet need in osteoarthritis where there have been drugs for controlling the signs and symptoms, even though they've had serious adverse events that limits their use. There really hasn't been a drug that changes the course of the disease and disease modification in osteoarthritis is you got to help the patients feel better regarding their pain and improve function, but you also should show structural benefit, because that's what the damage is happening in the knee.
So, lorecivivint is an injection that we've developed and we studied so far in one injection out to six months and one year, and we finished 1 phase one study and to phase two studies and we're presenting some of the face to data here at the ACR meeting.
What is shown is that the one injection given to the patients more painful knee improves the pain and function out to six months and maintain out to 12 months in most of the patients. Also, we've shown improvement in joint space as measured by the X ray at one year too. Especially in patients who have unilateral osteoarthritism because this is an injection given into a single knee. It also had very good safety profile so far—where the overall adverse event percentage is no different than placebo, the serious adverse events are very low. Again, none of the serious adverse events were deemed to be related to the drug by the investigators.
So this has prompted us to go into phase 3 pivotal trials and we have started our first pivotal trial, which is a 12 month trial again, similar to our phase 2—where the patients will get one injection of 0.7 milligrams of lorecivivint versus placebo injection. Then, we're going to follow these patients over one year and the primary outcome is looking at pain and function at 12 weeks and radiographic improvement and the structural inhibition of such a progression at 12 months.
We have a second pivotal trial that's going to start the first quarter of next year—in 2020, which is a six month trial, looking at signs and symptoms again at 12 weeks and maintaining the benefit hopefully out to 6 months.
We just completed enrollment in our third study, where we're looking at two injections, one injection at baseline, one injection at six months, and following patients out to 12 months, which will give us idea about the safety of using this drug with multiple injections.
In animal studies, we've injected it as frequently as once a month into animals and looking at the toxicology studies and we haven't seen any issues, but we also want to be able to provide the physicians the comfort that if the patient needs a second injection, it is safe to administrate and that study will help us answer that question.