Skip to content

4 Approaches to Treating Duchenne Muscular Dystrophy Highlighted at PPMD Conference

July 26, 2018

Discussions of the work being done on four different approaches to treating Duchenne muscular dystrophy (DMD) — repairing or replacing dystrophin, managing inflammation, improving muscle mechanics, and editing dysfunctional genes using CRISPR/CAS9 — were a highlight of sessions at the recent 2018 Parent Project Muscular Dystrophy (PPMD) conference in Scottsdale, Arizona.

Patients, parents, doctors, researchers, and industry executives gathered at the conference to share news and listen to sessions, including four led by pharmaceutical and biotech companies reporting results of preclinical and clinical work on each of these four potential treatment methods for DMD.

Restoring or Replacing Dystrophin

Representatives from five companies working to develop treatments that restore or replace dystrophin, a protein that normally supports skeletal and cardiac muscle function but is dysfunctional in DMD patients, presented data from recent trials.

NS Pharma shared results from Phase 1/2 and Phase 2 (NCT02740972) studies of NS-065/NCNP-01, conducted in North America and Japan. The investigational therapy, which is designed to encourage cells to skip over a mutation in exon 53, seemed to allow patients to naturally develop a smaller, but somewhat functional, form of dystrophin. The randomized, placebo-controlled studies showed some evidence of a dose-dependent increase in the formation of the protein.

An open-label Phase 2 extension study (NCT03167255) is continuing to evaluate the therapy’s safety and potential effectiveness in 19 boys with DMD. All are being treated with a once-weekly intravenous injection of NS-065/NCNP-01 at either 40 mg/kg or 80 mg/kg for 72 weeks.

Wave Life Sciences presented data on a similar candidate, WVE-210201, targeting a mutation on exon 51. The data came from in vitro cellular studies and research done in mice. The company is currently enrolling patients, ages 5 to 12, in a randomized, double-blind, placebo-controlled Phase 1 trial (NCT03508947) at sites in the U.S., France, and the U.K. Wave Life is planning to research a new therapy targeting exon 53 in 2019.

Sarepta Therapeutics presented preclinical data on several candidates targeting different exons, and discussed a new open-label Phase 1 trial (NCT03375255) testing an exon 51-skipping potential treatment, SRP-5051. This study is enrolling male patients, ages 12 and older, at sites across the U.S.

The session briefly took a somber turn when a representative from Summit Therapeutics touched upon the company’s decision to discontinue its development of ezutromid based on Phase 2 trial data showing a lack of benefit to DMD patients.

The session ended with PTC Therapeutics addressing developments with Translarna (ataluren), approved in the EU as the first treatment targeting the underlying cause of DMD. Translarna is not approved for use in the U.S., but is expected to come under FDA review again in about a year.

A long-term, randomized Phase 3 trial (NCT03179631) testing Translarna’s effects on disease progression versus placebo is enrolling about 250 patients with nonsense mutations, ages 5 and older, across the U.S., Europe, Asia, and Australia.


Therapies targeting inflammation, such as glucocorticoids, have commonly been prescribed to DMD patients for decades. Research suggests they can help prolong patients’ ability to walk. But many patients — and parents — oppose their use due to concerns about side effects, such as bone loss and weight gain.

Five companies presented data on new and potentially different ways of treating inflammation in DMD patients.

Reveragen presented data from an open-label Phase 2a trial (NCT02760277) suggesting that vamorolone could be safer than existing steroids, such as prednisone. Researchers developed this potential treatment to be what is called a “dissociative steroid,” meaning that its potential effectiveness is chemically separated from potential side effects. The next trial testing this therapy, anticipated to start in 2019, will include DMD patients ages 2 to 4 and 7 to 18.

Catabasis presented Phase 2 trial data (NCT02439216) on edasalonexent, which inhibits a protein complex called the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB,) known to be involved in inflammation. The therapy showed potential to slow disease progression. A Phase 3 trial is also planned that will measure ambulatory and timed movement functions, and collect MRI scans of muscles to determine their fat fractions.

Italfarmaco discussed Phase 2 data (NCT01761292) on givinostat, a histone deacetylase (HDAC) inhibitor. Increased HDAC activity may trigger inflammation and prevent muscle regeneration in DMD patients. A randomized, double-blind, placebo-controlled Phase 3 trial (NCT02851797) is currently enrolling more than 200 ambulatory patients, ages 6 to 17, who will be given either 10 mg/mL of givinostat or a placebo twice daily. The study is taking place at sites in the U.S., Canada, and Europe.

Mallinckrodt Pharmaceuticals presented preclinical data on its anti-inflammatory candidate, MNK-1411, which received orphan drug designation from the U.S. Food and Drug Administration.MNK-1411 is thought to prevent inflammation by mimicking the adrenocorticotropic hormone, which regulates immune cell function. The company is beginning a Phase 2 trial (NCT03400852) in the U.S. in boys ages 4 to 8. Patients will be randomized to receive a high- or low-dose injection of MNK-1411 or a placebo twice a week.

Capricor shared preclinical and Phase 1/2 data (NCT02485938) suggesting that its cell therapy, CAP-1002, could reduce scarring on the heart, and possibly improve upper limb function. A Phase 2 trial (NCT03406780) is actively recruiting both ambulatory and non-ambulatory patients in the U.S. who will be randomized to receive either CAP-1002 or a placebo via intravenous infusion once every three months for 12 months.

Improving Muscle Mechanics

Five companies also presented data on therapies designed to improve muscle mechanics through a variety of mechanisms.

Roche/Genentech and Pfizer both outlined potential treatments that block myostatin, a molecule that tells muscles to stop growing. Roche/Genentech is recruiting ambulatory boys ages 6 to 11 for a Phase 2/3 trial (NCT03039686) in which patients will be randomized to receive 48 weekly injections of RG6206 (also known as BMS-986089) or a placebo. The study is being conducted in several countries, including the U.S., Australia, Argentina, and those in Europe.

Pfizer presented preclinical data for its myostatin-inhibiting candidate, domagrozumab. A randomized, double-blind, placebo-controlled Phase 2 trial (NCT02310763) evaluating its effectiveness for DMD is expected to conclude in late 2019.

Santhera shared results from its Phase 3 DELOS trial (NCT01027884), suggesting that idebenone may delay the loss of respiratory function in DMD patients who aren’t taking steroids. The company is now conducting another Phase 3 trial, SIDEROS (NCT02814019), which is enrolling ambulant and non-ambulant patients, 10 years and older, currently on steroid treatment, in the U.S. and Europe. Participants will be randomized to take idebenone or a placebo daily for 18 months. The therapy is not yet approved in the U.S. but has become available under an expanded access program, in the country, but an advisory committee in Europe twice recommended against its approval for DMD.

Phrixus Pharmaceuticals presented preclinical data on its Carmaseal-HD therapy, a daily injection that may modify the course of the disease by repairing membrane damage. The company hopes the therapy will benefit patients regardless of their individual genetic mutation. The first clinical trial — an open-label Phase 2 study (NCT03558958) — is currently enrolling up to 10 non-ambulatory patients, ages 12 to 25, with respiratory dysfunction, who will take the therapy once a day for 52 weeks at Cincinnati Children’s Hospital.

FibroGen discussed its potential fibrosis-preventing therapy, pamrevlumab. The therapy has been tested in trials involving patients with pancreatic cancer and pulmonary fibrosis for safety, and an open-label Phase 2 trial (NCT02606136) in 22 non-ambulatory DMD patients ages 12 and older in the U.S. is ongoing. Patients are receiving a biweekly intravenous infusion of the therapy for up to 156 weeks.

Gene Editing

The research portion of the conference ended with a panel on gene editing techniques.Dongsheng Duan, PhD; Jeff Chamberlain, PhD; and Melissa Spencer, MD, PhD, tentatively discussed their work and answered questions about CRISPR/CAS9, the breakout gene editing technique adapted about five years ago. While enthusiastic, the presenters were careful to remind parents and patients that forgoing standard DMD care while waiting for CRISPR-based therapies to be developed would not be wise.

Researchers are hopeful that CRISPR/CAS9 may be used to delete mutated genes in DMD, or possibly replace them with genes that encode functional proteins. One of the struggles is designing a delivery system. Some scientists are using viruses to deliver the gene editing molecules, while others are working to develop nanoparticles that might be tailored specifically for this purpose.

It will be crucial to selectively edit muscular cells, which are less susceptible than others to the risks of gene editing, such as cancer cells. The researchers showed promising animal data, but again emphasized that the technique has a way to go before it might benefit patients.