Rare Disease Report

Duchenne Drugs in The Pipeline

OCTOBER 26, 2016
James Radke, PhD
Until the recent approval of eteplirsen to treat a subset of Duchenne muscular dystrophy (DMD) patients (those amenable to exon 51 skipping therapy), the only treatment commonly used in DMD patients were corticosteroids, which are associated with a number of negative side effects.
And as our understanding of the pathophysiology and natural history of DMD patients has expanded, so have the number of treatment options in development. Even with eteplirsen’s approval and the hope that other exon skipping drugs will become available, those drugs do not cure the patient. Other treatments are needed.
A recently published review article in Expert Opinion of Orphan Drugs, Drs Spinazzola and Kunkel provide an overview of the leading drugs in development for treating the secondary effects of DMD. In other words, the authors focused on drugs in development outside of genetic manipulation (i.e., gene therapy, exon-skipping therapy).  In total, the authors summarized 41 drugs in development to treat DMD patients. A few of those in later stage development are discussed below.


The only treatment currently used by almost all DMD patients is long-term use of glucocorticoids such as prednisone, prednisolone, or deflazacort. These drugs are thought to function primarily by inhibiting the NF-κB pathway. In clinical studies, these drugs prolong independent ambulation, improve pulmonary function, and delay the onset of cardiomyopathy. On the downside, they have significant side effects including weight gain, hypertension, and vertebral compression fractures.
Recently, ReveraGen has developed Vamorolone (previously known as VBP15), a novel glucocorticoid analogue that retains the anti-inflammatory characteristics of traditional DMD corticosteroid treatments, but without significant side effects. It is currently in Phase 2 studies.

Targeting NF-κB

Catabasis has developed an NF-κB inhibitor, CAT-1004. In animal models, it reduced muscle degeneration and improved muscle regeneration and function in skeletal, diaphragm, and cardiac muscle. A phase 1 / 2 clinical trial is currently underway.

Promoting muscle mass

Myostatin is a negative regulator of skeletal muscle growth. As such, inhibition of this protein would, in theory, attenuate the lost muscle mass seen in DMD patients. 
Attempts to develop a drug that blocks myostatin have been fraught with problems but recently, Bristol-Myers Squibb and Pfizer have separately developed an anti-myostatin antibodies (BMS-986089 and PF-06252616, respectfully) that are in clinical trials.

Other targets

In addition to these drugs, there are numerous drugs in early stage development to treat DMD, including drugs that target fibrosis, calcium regulation, and oxidative stress. Generally, these drugs have shown promise in animal models but clinical trials in humans have been limited or have not yet begun.  Phosphodiesterase inhibition is also thought to be a possible target but a recent phase 3 study with tadalafil failed to meet its primary endpoint in DMD patients.

The authors finished their review by noting that while many drugs seem promising in DMD animal models, the number of drugs that have successfully made it past a phase 1 or 2 trial is extremely small. However, the authors concluded that “while there are certainly challenges associated with delivery, tolerance, and consistent efficacy, there are more potential treatments than ever before, some of which may have significant impact on disease progression.”
Our readers are strongly encouraged to read this thoughtful and thorough review by Drs Spinazzola and Kunkel.


Spinazzola JM, Kunkel LM. Pharmacological therapeutics targeting the secondary defects and downstream pathology of Duchenne muscular dystrophy. Exp Opin Orphan Drugs. 2016;4:1179-1194. http://dx.doi.org/10.1080/21678707.2016.1240613

Stay informed on the latest rare disease news and developments by signing up for our newsletter.
Copyright © RareDR 2013-2018 Rare Disease Communications. All Rights Reserved.