Type of information: Establishment of a new subsidiary in the EU
Product name: Emflaza™
Therapeutic area: Rare diseases - Genetic diseases - Neuromuscular diseases
Action mechanism: corticosteroid. Deflazacort is a glucocorticoid with anti-inflammatory and immunosuppressant properties.
Company: Marathon Pharmaceuticals (USA - IL)
Disease: Duchenne muscular dystrophy (DMD)
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. The FDA granted this application fast track designation and priority review. The drug also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. Marathon Pharmaceuticals is receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive priority review of a subsequent marketing application for a different product. This is the ninth rare pediatric disease priority review voucher issued by the FDA since the program began.
- • On February 9, 2017, the FDA approved Emflaza™ (deflazacort) tablets and oral suspension to treat patients age 5 years and older with Duchenne muscular dystrophy. It works by decreasing inflammation and reducing the activity of the immune system. This is the first FDA approval of any corticosteroid to treat Duchenne muscular dystrophy and the first approval of deflazacort for any use in the United States.
Marathon has requested authorization from the FDA to provide deflazacort as an investigational drug to qualified patients with DMD at no cost, through an expanded access program (EAP). FDA indicated that it may formally authorize this program pending a full review of the EAP protocol. If the program is authorized by FDA, doctors will be able to enroll qualified patients to receive this investigational* medication beginning in September 2015.
- • On June 14, 2016, Marathon Pharmaceuticals announced it has submitted a New Drug Application (NDA) to the FDA for deflazacort for the treatment of patients with Duchenne muscular dystrophy. The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing. The NDA filing is supported by a full preclinical and clinical study program, including two pivotal clinical efficacy trials exclusively licensed by Marathon in more than 200 Duchenne patients 5 to 15 years of age. These data show that deflazacort improved muscle strength and other functional outcomes in patients with Duchenne regardless of genetic etiology and in one of the studies ambulation status.1 Marathon additionally conducted seven clinical pharmacology and safety studies of deflazacort and nine preclinical studies to support either the initiation of clinical studies or marketing approval. An expanded access program, Access DMD™, is ongoing in the United States and provides deflazacort to patients with Duchenne free of charge during the NDA review process.
- • On August 5, 2015, Marathon Pharmaceuticals announced that the company will begin the New Drug Application (NDA) process for deflazacort as a potential treatment for patients with Duchenne muscular dystrophy (DMD) following a positive pre-NDA meeting with the FDA. The deflazacort NDA is expected to be submitted in the first quarter of 2016 and will be subject to review by the FDA. If approved, deflazacort is expected to be made commercially available in the U.S. in the first quarter of 2017. The FDA previously granted Fast Track status and Orphan Drug designation for deflazacort for the treatment of patients with DMD.
Submission of marketing authorization application USA : 2016-06-14
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-02-09
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2013-08-16
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: