Flavocoxid Well-tolerated, Lessens Inflammation in Small DMD Trial

Flavocoxid was well-tolerated and lessened inflammation in a small clinical trial involving boys with Duchenne muscular dystrophy (DMD).

Researchers said these results support Flavocoxid’s further investigation as a potential DMD therapy.

The findings were published in the journal Brain Sciences, in “A Phase 1/2 Study of Flavocoxid, an Oral NF-κB Inhibitor, in Duchenne Muscular Dystrophy.”

One of the characteristic biological features of muscular dystrophy is inflammation, which can contribute to muscle deterioration. This is a large part of why steroid therapies, such as corticosteroids, can be therapeutic in DMD and other muscular dystrophies.

Flavocoxid is a medical food containing plant extracts that have anti-inflammatory and antioxidant properties. It has been shown to have beneficial effects such as reducing inflammation and improving muscle function in mouse models of DMD.

Now, a team of researchers in Italy conducted a Phase 1 clinical trial (NCT01335295), sponsored by the University of Messina, in Sicily, to evaluate flavocoxid in boys with DMD.

The trial enrolled 34 boys, ages 4 to 12. Half of the participants were given flavocoxid twice daily, with dosages based on the individual’s body weight. The other half received no treatment and served as controls.

The participants were followed for one year. Most of the boys, including nine in the flavocoxid group, were taking steroid therapies.

The trial’s main goal was to assess the safety profile of flavocoxid, and those results were positive. None of the participants dropped out of the trial, and all reported adverse events — which included cough, diarrhea, headache, and fever — were deemed unrelated to flavocoxid treatment. The treatment also did not significantly impact markers of muscle or liver damage.

“In our pediatric DMD cohort [group], flavocoxid was well tolerated, adverse events related to the treatment were not recorded, and nobody left the study,” the researchers wrote.

Among the boys given steroid therapy, treatment with flavocoxid significantly reduced markers of inflammation — specifically interleukin-1-beta and tumor necrosis factor alpha — after six months. However, the levels of these markers were not significantly altered after one year. In boys given flavocoxid who were not on steroid therapy, there were no changes found in inflammatory markers.

In individuals without steroid therapy, flavocoxid treatment significantly reduced blood levels of markers of oxidative stress at six months and one year.  These markers occur when antioxidant defenses do not effectively protect against oxidant molecules. No significant changes were seen for boys on steroids.

Notably, the decrease in inflammatory and oxidative stress markers at six months was significant in boys younger than 7, but not for older participants.

“On the one hand, these findings confirm that flavocoxid has anti-inflammatory and antioxidant activities in DMD boys as well, while on the other hand, it was able to exert anti-inflammatory effects only if combined with steroids, and for a limited period of time, but a definite antioxidant property when applied alone and for the entire treatment period,” the researchers wrote.

As for the greater benefits shown when starting treatment at an earlier age, these findings confirm “what is known for steroids in younger DMD boys,” the team added.

Various tests of motor and lung function were conducted among study participants. Flavocoxid did not cause significant changes in any of the tests measured. However, the researchers highlighted non-significant trends toward beneficial effects for some measures. Specifically, these were speed on the Gowers’ maneuver in younger participants, and the 10-meter walk test in older boys.

The scientists noted that this study was fairly small, and the duration was fairly short, limiting its statistical power to detect significant effects on motor function. A longer study with more participants likely would help researchers determine whether flavocoxid can improve motor function in DMD boys, the team speculated.

Flavocoxid also may have use as an alternative to steroids, which can cause side effects like weight gain, excessive hair growth, cataracts, and increased risk of broken bones, the researchers said.

“A further double-blind, placebo-controlled study for at least two/three years is warranted to verify its [flavocoxid’s] potential as a steroid substitute or as an add-on therapy to steroids,” they concluded.

In the U.S., flavocoxid has been marketed under the brand name Limbrel, which was used to manage a form of arthritis. Limbrel’s manufacturer, Primus Pharmaceuticals, withdrew the product from the market in 2018, after concerns were raised about allergic reactions and liver injury.

Limbrel remains off the market. However, according to the investigators, recent data have indicated that flavocoxid use is associated with a low incidence of a rare form of lung inflammation and liver injury.

“The risk-benefit profile of flavocoxid may warrant re-evaluation based on these findings,” the researchers wrote.