On February 9th, 2017 the U.S. Food and Drug Administration (FDA) approved Emflaza® (deflazacort) tablets and oral suspension to treat patients age 5 years and older with Duchenne muscular dystrophy (DMD), a rare genetic disorder that causes progressive muscle deterioration and weakness. Emflaza® is a corticosteroid that works by decreasing inflammation and reducing the activity of the immune system. Corticosteroids are commonly used to treat DMD across the world. This is the first FDA approval of any corticosteroid to treat DMD and the first approval of deflazacort for any use in the United States. Emflaza® is manufactured and distributed by Marathon Pharmaceuticals of Northbrook, Illinois. Deflazacort was given fast-track designation and priority review by the FDA. The drug also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

DMD is a rare genetic disorder that causes progressive muscle deterioration and weakness. The first symptoms typically appear between age 3 and 5 years and worsen over time. The disease primarily affects boys. Estimates are that DMD occurs in about 1 of every 3600 male infants worldwide. Duchenne, a severe form of muscular dystrophy, is a rare disease and fatal genetic disorder that affects about 15,000 people in the United States. It typically results in the inability to walk by the teen years or earlier, and severe respiratory and cardiac complications that lead to death generally between the late teens and early twenties. However with advanced care, longevity of life may be increasing. Thanks to advances in cardiac and respiratory care, life expectancy is increasing and many young adults with DMD attend college, have careers, get married and have children. Survival into the early 30s is becoming more common, and there are cases of men living into their 40s and 50s. For more about living with DMD.

Duchenne muscular dystrophy was first described by the French neurologist Guillaume Benjamin Amand Duchenne in the 1860s, but until the 1980s, little was known about the cause of any kind of muscular dystrophy. In 1986, MDA-supported researchers identified a particular gene on the X chromosome that, when flawed (mutated), leads to DMD. In 1987, the protein associated with this gene was identified and named dystrophin. Lack of the dystrophin protein in muscle cells causes them to be fragile and easily damaged. DMD has an X-linked recessive inheritance pattern and is passed on by the mother, who is referred to as a carrier. DMD carriers are females who have a normal dystrophin gene on one X chromosome and an abnormal dystrophin gene on the other X chromosome. Most carriers of DMD do not themselves have signs and symptoms of the disease, but a minority does. Symptoms can range from mild skeletal muscle weakness or cardiac involvement to severe weakness or cardiac effects and can begin in childhood or adulthood.

The effectiveness of deflazacort was shown in a clinical study of 196 male patients who were 5 to 15 years old at the beginning of the trial with documented mutation of the dystrophin gene and onset of weakness before age 5. At week 12, patients taking deflazacort had improvements in a clinical assessment of muscle strength across a number of muscles compared to those taking a placebo. An overall stability in average muscle strength was maintained through the end of study at week 52 in the deflazacort-treated patients.

In another trial with 29 male patients that lasted 104 weeks, deflazacort demonstrated a numerical advantage over placebo on an assessment of average muscle strength. In addition, although not statistically controlled for multiple comparisons, patients on deflazacort appeared to lose the ability to walk later than those treated with placebo.

The side effects caused by Emflaza® are similar to those experienced with other corticosteroids. The most common side effects include facial puffiness (Cushingoid appearance), weight gain, increased appetite, upper respiratory tract infection, cough, extraordinary daytime urinary frequency (pollakiuria), unwanted hair growth (hirsutism) and excessive fat around the stomach (central obesity). Other side effects that are less common include problems with endocrine function, increased susceptibility to infection, elevation in blood pressure, risk of gastrointestinal perforation, serious skin rashes, behavioral and mood changes, decrease in the density of the bones and vision problems such as cataracts. Patients receiving immunosuppressive doses of corticosteroids should not be given live or live attenuated vaccines.

As always, readers of this blog are highly encouraged to read the complete sources/references listed below thoroughly and in full to contextualize the complete information provided. Additionally, interested parties on this topic important topic about DMD should seek further information on this topic from scientific and medical information readily available in the public domain.

Links/References:

  1. https://www.mda.org/disease/duchenne-muscular-dystrophy
  2. http://marathonpharma.com/news/2017/02/emflaza-deflazacort-just-fda-approved/
  3. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm540945.htm
  4. http://www.medscape.com/viewarticle/875608?nlid=112585_3901&src=wnl_newsalrt_170209_MSCPEDIT&uac=239333AV&impID=1287645&faf=1