Susan Perlman, MD, discusses the side effects of Skyclarys and the best ways to manage them. She also addresses the general timeline for how long side effects should last.

Skyclarys, you know, for the past year, has been the only approved drug for Friedreich’s ataxia. It addresses the mitochondrial dysfunction that the frataxin protein deficiency causes. It activates a pathway in the mitochondrion that enables the mitochondrion to fight back against oxidative stress, free radicals, things that compromise on the performance and energy production, and ultimately, nerve performance, as we have mentioned.

So most drugs come with side effects. This is fortunately an oral medication. The common side effects seen in the first one to two months would be headache, muscle and joint pain, abdominal pain, nausea, and fatigue.

So usually after somebody has been on the drug for a couple of months, these will be declining and will not be particularly bothersome. One thing that does have to be monitored is liver function. There are several markers in blood work that seem to go up when somebody is placed on this drug. One is the transaminases, the SGOT and SGPT. Also, there could be elevations in a cardiac biomarker called BNP, as well as elevations in cholesterol and lipid measures.

We don’t know fully why the lipids go up. We don’t know 100% the meaning of the elevated cardiac BNP, which is a marker of cardiac stress. The heart puts it out and sends the BNP to the kidneys to aid diuresis to reduce fluid load and fluid stress.

So normally, it’s put out by the heart when it’s under stress. Similarly with the transaminases in the liver, when the liver is working harder, the transaminases may go up. They’re not a sign of liver damage. They’re just a sign the liver is working harder because of a drug. So when you think about the presence of the mitochondria in the liver, in the heart, we pump up the activity of the mitochondria and those organs may respond as if they’re doing a stress response using biomarkers of liver compromise or cardiac compromise.

Fortunately, in the studies that were done as part of the MOXIe trial, there weren’t any signs of liver damage. There weren’t any elevations of bilirubin, there weren’t any elevations of ALT and AST. And with the elevations of BNP in a small percentage of patients, the heart performance was stable. So it was not an indicator that the heart was giving up, but potentially just that the heart was working harder through its mitochondria.