Familial Mediterranean Fever: Minimizing Inflammation and Preventing Flares

Familial Mediterranean Fever (FMF) is a genetic disease that presents in recurrent self-limited attacks of fever and inflammation in the serosal membranes, joints, and skin. Rheumatology Network interviewed Nihar Bhakta, MD, Chief Medical Officer of Aristea Therapeutics, to discuss this rare rheumatic disease and how Aristea Therapeutics is working to treat patients suffering from this condition.

Nihar Bhakta, MD: Patients can have inflammation and swelling in their joints. Typically, the larger joints, but sometimes some patients have it in the smaller joints, like the hands, as well. The most prevalent feature is the spikes of fever they can develop, which can be relatively high. A lot of the patients also get inflammation in their serosal membranes, which are the membranes that lie in the abdomen or lungs. They can also develop inflammation around the lining of their heart, leading to chest pain.

Rheumatology Network: How common is this disease?

NB: It’s relatively rare, affecting probably less than 10,000 patients in the United States. However, it’s a bit more common, as the name would suggest, in areas around the Mediterranean. It’s more prevalent in Israel, Turkey, Italy, and Persian countries.

RN: What is the current treatment plan for patients with FMF?

NB: The disease was identified almost 60 years ago, and treatment has been pretty much the same since then. Colchicine is the first line therapy for these patients. Colchicine can affect short-term inflammation, but really, these patients should remain on the drug long-term to avoid chronic complications. These attacks of inflammation can cause something called amyloidosis, which can lead to the deposition of proteins in the kidneys and heart.

RN: How does Aristea help treat and manage patients with this condition?

NB: There are about 5-10% of patients who continue to have recurrent or sporadic attacks despite receiving colchicine. The goal with colchicine treatment is to have 1 or fewer attacks in any given year. We know that some patients are going to have breakthrough attacks, but the goal is to try to keep them completely attack free, if possible.

For that smaller subset of patients who continue to have attacks despite being on a tolerated dose of colchicine, we want to implement our therapy, a CXCR2 antagonist, in addition to colchicine. Data suggests that neutrophils are an important component of the inflammation that these patients have. If you were to obtain fluid from the joints of these patients when they are swollen, it would be full of neutrophils. What our molecule does is it blocks the migration of neutrophils from the bone marrow out into the bloodstream and ultimately out of the areas of inflammation. And our hope is that our therapy, in combination with colchicine, can keep patients who were previously having attacks while on colchicine, attack-free through their treatment period.

RN: What are the next steps for your team? Does your team plan on doing any further research on this

topic?

NB: Yes, we are conducting a phase 2 clinical trial in patients with Familial Mediterranean Fever, and we're really excited about this study. It's being conducted in Turkey and Israel, because that's where the there's a higher prevalence, and it’s a relatively small pilot study to determine if our molecule works in combination with colchicine. It's predominantly a safety study. We want to make sure that the combination is safe in these patients, determine the efficacy, and reduce the number of flares in this patient population.

The initial trial is a 3-month study, but we are hopeful that we'll be able to get our clinical trial applications approved so that we can look at longer term dosing as well. Ideally, we're going to be dosing these patients for longer than 1 year with our therapy to see how long we can keep them attack-free.

RN: Is there anything else that you'd like our audience to know?

NB: Aristea is very committed to the evaluation of autoinflammatory conditions. We think many of these conditions, including Familial Mediterranean Fever, may benefit from having some degree of neutrophil blockade. We're also looking at other diseases, including Behcet’s disease, which is another rare rheumatologic condition. We're planning on conducting a study that will likely start next year in which we’re looking at patients who are not doing well on the current standard of care, which is colchicine, and adding our therapy.