Emflaza (deflazacort), originally developed by Marathon Pharmaceuticals and later acquired by PTC Therapeutics), is a therapy to treat Duchenne muscular dystrophy (DMD) in patients, 2 or older, regardless of disease-causing genetic mutation. Emflaza has been approved by the U.S. Food and Drug Administration (FDA) to treat DMD.
How Emflaza works
DMD is a type of muscular dystrophy, a group of diseases characterized by muscle weakness and atrophy. DMD is caused by mutations in the gene that encodes for dystrophin, an important structural protein that provides support for muscle cells as they stretch and contract with motion. The mutation causes the dystrophin protein to be absent, causing muscle cells to become damaged at each contraction and eventually die.
One factor that is thought to contribute to disease progression in DMD is inflammation. While inflammation normally triggers healing processes in the body, the over-activation of the immune system promotes the breakdown of muscle cells and can speed the progression of DMD.
Emflaza is a pro-drug, meaning that the therapy must be metabolized in the body into its active form. Emflaza contains a pro-corticosteroid, which, once metabolized, becomes a corticosteroid — a synthetic molecule that resembles an anti-inflammatory hormone naturally produced by the body. Once metabolized to its active form, Emflaza acts to suppress the immune system.
The precise mechanism by which Emflaza slows the progression of DMD is unclear, but its effect is thought to be mediated by the suppression of the immune system, thereby reducing muscle damage.
Emflaza in clinical trials
The FDA approval of Emflaza was based on the results of a Phase 3, randomized, double-blind, placebo-controlled clinical trial (NCT01603407) that took place in the U.S. and Canada. This 52-week study included 196 boys with DMD, ages 5 to 15.
In the first part of the trial, patients received either Emflaza (0.9 or 1.2 mg per kg of body weight each day), a comparable corticosteroid (prednisone), or a placebo for 12 weeks. In the second part, patients who took a placebo received either Emflaza or prednisone for 40 weeks. Participants already on active treatment (Emflaza or prednisone) continued on that treatment.
The primary outcome measure of the trial was average muscular strength. The change in muscle strength was found to be significantly greater at week 12 in boys taking Emflaza at a dose of 0.9 mg per kg per day compared with a placebo. No significant additional benefit was seen in the higher dose group. Muscle strength continued to increase through week 52, demonstrating the persistence of the treatment’s beneficial effect.
Several assessments of the participants’ function (measured by the time to stand from a supine position, time to climb four stairs, and time to walk or run 30 feet) also favored Emflaza (at 0.9 mg per kg) at week 12 compared with a placebo.
Participants who were taking Emflaza also gained less weight than those taking prednisone. The most frequent adverse events for all the participants on treatment were Cushingoid appearance, rash, hair growth, increased weight, headache, and colds.
This Phase 3 study was completed in 1995, but the results were published in November 2016 in the journal Neurology as the original trial sponsor was purchased by another company that decided not to pursue its development in the U.S.
A more recent study (NCT02251600) in 24 boys with DMD, ages 4 to 16, evaluated Emflaza in comparison to a placebo for two years. Improvement in muscle strength did not reach statistical significance, possibly because of the limited number of patients taking the placebo, but it favored Emflaza treatment.
An open-label, long-term extension (NCT02295748) of this trial was also performed, and an expanded access program (NCT02592941) was approved for marketing to increase treatment access for DMD patients who were unable to join another clinical trial.
Finally, Emflaza is being studied (NCT03783923) in patients with limb-girdle muscular dystrophy 2I (LGMD2I). This trial is currently recruiting around 100 participants to test Emflaza versus a placebo in a double-blind phase for 26 weeks and then continue in an open-label phase for another 26 weeks. Results of this study are expected in August 2020.
Emflaza is the first FDA-approved corticosteroid to treat DMD patients and the first approval of Emflaza for any use in the U.S.
Common side effects of Emflaza include facial puffiness, weight gain, increased appetite, upper respiratory tract infections, coughing, frequent daytime urination, unwanted hair growth, and central obesity.
Because Emflaza suppresses the immune system, patients are not advised to be vaccinated with live or live-attenuated vaccines. New or booster vaccinations should be discussed with a doctor.
Last updated: 07/11/2019
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