Top 10 Muscular Dystrophy Stories of 2020

Throughout 2020, Muscular Dystrophy News Today brought you daily coverage of important discoveries, treatment advancements, clinical trial findings, and other relevant events related to muscular dystrophy.

As we look forward to bringing you more news this year, we present here the 10 most-read stories of 2020, along with a short summary of what made them relevant to the patient community. Several of the stories focused on new forms of gene therapy now in development for Duchenne (DMD).

No. 10 – “Hansa Licenses Imlifidase to Sarepta as Gene Therapy Pre-treatment for DMD, LGMD”

In July, we covered the worldwide licensing of Hansa Biopharma’s imlifidase to Sarepta Therapeutics. That deal allowed imlifidase to be developed as a gene therapy pre-treatment for those with DMD and limb-girdle muscular dystrophy (LGMD) who would otherwise be unable to receive such therapies.

Imlifidase is an enzyme that’s able to quickly break down immunoglobulin G antibodies, a type of antibody found in the bloodstream that can inactivate the viral vectors most gene therapies use to deliver gene constructs to cells. As such, imlifidase is expected to suppress patients’ immune responses against these viral vectors, making them eligible for gene therapy.

No. 9 – “Cure Rare Disease’s Rich Horgan Pioneers Customized Medicine to Treat Brother with DMD”

Muscular Dystrophy News Today talked last January with Rich Horgan, the founder of the nonprofit organization Cure Rare Disease, which he created in 2017 to help scientists develop personalized therapies for people with rare disorders — with a main focus on those with DMD. Rich’s younger brother, Terry, who has a form of DMD that cannot be treated by currently approved therapies due to the specific type of genetic mutation he carries, served as inspiration for the nonprofit’s launch.

To help patients like Terry, Cure Rare Disease has partnered with scientists who are attempting to use the CRISPR/Cas 9 gene-editing tool to correct each of these genetic defects. If this approach proves to be successful in animal models, Terry may become the first patient in the U.S. to be treated with CRISPR. In addition to Terry, three other patients are currently in line to receive this customized therapy.

No. 8 – “Phase 1 Results Support Losmapimod as FSHD Treatment”

Fulcrum Therapeutics presented data in March from a Phase 1 trial that supported losmapimod’s development as a therapy for facioscapulohumeral muscular dystrophy (FSHD). Losmapimod is an oral selective inhibitor of two proteins that normally control the activity of the DUX4 gene, which is overly active in people with FSHD.

Data from this Phase 1 trial showed losmapimod had a favorable safety profile that was consistent with previous reports in other indications and among healthy volunteers. Moreover, trial investigators found that, in patients’ blood and muscle tissue, the experimental therapy was able to engage with its intended target in a dose-dependent manner. Results from this study also backed up losmapimod’s twice daily 15 mg dose, which was selected to be used in other clinical trials.

No. 7 – “Phase 2b Trial of Fulcrum’s Oral FSHD Treatment, Losmapimod, Fully Enrolled”

We reported in February that a Phase 2b trial of losmapimod, called ReDUX4 (NCT04003974), was fully enrolled. Sponsored by Fulcrum, the study was designed to evaluate the safety and pharmacological properties of losmapimod in around 80 adults with FSHD. In addition, the trial will investigate whether losmapimod is better than a placebo at lowering the activity of DUX4, when given twice daily at a dose of 15 mg for 48 weeks (nearly one year).

Fulcrum also announced at the time that it had started dosing participants who completed ReDUX4 and were entered in its open-label Phase 2 extension study (NCT04264442). These patients will continue treatment with losmapimod for an additional period of approximately one year.

No. 6 – “Pfizer’s Gene Therapy for Duchenne Placed on Fast Track by FDA”

The U.S. Food and Drug Administration (FDA) in October granted fast track status — a designation that aims to accelerate the development and approval of promising treatments for serious medical conditions — to PF-06939926, Pfizer’s experimental gene therapy for DMD. PF-06939926 is a one-time treatment that uses a harmless version of an adeno-associated virus, called AAV9, to deliver a shorter but functional version of the DMD gene, faulty in people with Duchenne, specifically to muscle cells. By doing so, PF-06939926 is expected to halt, or at least slow, muscle degeneration in these patients.

The FDA’s decision was based on data from a Phase 1b trial (NCT03362502) that showed that a single dose of the therapy was safe and able to improve motor function in a small group of boys with DMD. The trial findings also demonstrated that PF-06939926 promoted the production of micro-dystrophin — a shorter but working version of the protein missing in people with DMD — in boys’ muscle tissues. The therapy had previously been named an orphan drug in the U.S. and Europe, and had received rare pediatric disease designation from the FDA.

No. 5 – “Sarepta’s Gene Therapy for DMD Showing to Safety, Efficacy at One Year”

One-year data from a Phase 1/2 trial (NCT03375164) of SRP-9001, Sarepta’s investigational micro-dystrophin gene therapy, continued to support the treatment’s potential for those with DMD. Like other forms of gene therapy, SRP-9001 uses a harmless AAV vector — here, rAAVrh74 — to deliver micro-dystrophin to muscle cells. In agreement with previous reports, the data showed that a single dose of SRP-9001 was sufficient to deliver the modified DMD gene copy to muscle cells and induce the production of the micro-dystrophin protein in all four boys participating in the trial. SRP-9001 also was found to be safe, to improve the boys’ motor abilities, and to lower the levels of creatine kinase, a marker of muscle damage and inflammation.

SRP-9001’s safety and efficacy also are being investigated in a larger group of 41 DMD boys participating in a Phase 2 trial (NCT03769116), also sponsored by Sarepta.

No. 4 – “PerkinElmer Launches New Genetic Test for FSHD Type 1”

In March, we covered the launch of PerkinElmer Genomics’ new genetic test for FSHD type 1. This disease type, the most common form of FSHD, is caused by the loss of gene repeats in a region of chromosome 4 called D4Z4. The new test uses Bionano Genomics’ Saphyr system to create an accurate visual representation of the D4Z4 region.

When performed on a person suspected of having FSHD, this new genetic test can indicate if gene repeats are missing, thereby confirming the diagnosis of FSHD. PerkinElmer had previously developed a blood spot-based test for DMD screening in newborns, and is planning to launch additional genetic tests to help identify FSHD and other neuromuscular diseases.

No. 3 – “FDA Accepts New Drug Application for Potential DMD Treatment Viltolarsen”

Nippon Shinyaku, the parent company of NS Pharma, announced early in the year that the FDA had agreed to review its application requesting the approval of viltolarsen for the treatment of DMD patients who are amenable to exon 53 skipping. Viltolarsen is designed to allow cell machinery to skip over exon 53 — one of the coding regions in the DMD gene that is sometimes mutated in people with DMD — to produce a fully functional version of dystrophin.

That request was supported by data from a Phase 2 trial (NCT02740972) conducted in North America and from a Phase 1/2 study in Japan. Data from the Phase 2 trial showed that, when given by intravenous (into-the-vein) infusion, viltolarsen increased dystrophin production in the muscles of boys, ages 4–10, with DMD.

The FDA conditionally approved viltolarsen — now known as Viltepso in the U.S. — a few months later, in August. The therapy’s full approval is now pending confirmation of its safety and efficacy in an ongoing Phase 3 trial, called RACER53 (NCT04060199), which is still recruiting in several countries worldwide. RACER53 aims to enroll 74 boys with DMD, ages 4–7, who are able to walk by themselves. More information about enrollment sites can be found here.

No. 2 – “Combo Treatments, Gene Therapies and What’s Ahead for Muscular Dystrophy: Talk with MDA”

A February Muscular Dystrophy News Today interview with Sharon Hesterlee, PhD, executive vice president and chief research officer for the Muscular Dystrophy Association (MDA), focused on the challenges that gene therapies for rare neuromuscular disorders are currently facing. According to Hesterlee, there are two main hurdles gene therapies must yet overcome. One is the technical challenges that limit these treatments from reaching all intended target tissues and organs. The other is that many of these therapies likely will have to be given more than once over a person’s lifetime.

Hesterlee said researchers worldwide are working to find solutions, stressing that the MDA has financially supported many gene therapy candidates currently in development for DMD — particularly those based on mini-dystrophin gene constructs — and other forms of muscular dystrophy. She also pointed out that the combination of gene therapies with small molecule compounds likely will be “the future.”

No. 1 – “Pfizer’s DMD Gene Therapy Continues to Show Promise, Phase 1b Trial Shows”

Our most-read story of 2020 covered Pfizer’s announcement of one-year data from a Phase 1b trial (NCT03362502) assessing the safety and efficacy of a one-time intravenous (into-the-vein) infusion of PF-06939926, the company’s investigational gene therapy for DMD, in a small group of boys with Duchenne. Earlier data from the first six boys treated in the study showed PF-06939926 was safe and able to induce the production of micro-dystrophin in muscle tissues over six months.

The updated findings included data from three boys treated with the low dose — 1E14 vector genomes per kilogram (vg/kg) — of PF-06939926 and six with the high dose (3E14 vg/kg). These early results showed the therapy continued to be safe and to promote mini-dystrophin production in muscle tissues in a dose-dependent manner. Compared with other boys treated with a placebo in previous trials, those receiving PF-06939926 in this study also saw their motor abilities improve and the amount of muscle fat in their thighs diminish.

Altogether, these findings suggested PF-06939926 may help improve muscle fibers’ overall health and supported its continued development as a DMD gene therapy.

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At Muscular Dystrophy News Today, we hope these top 10 news articles and our reporting throughout the year contributed to informing and improving the lives of everyone with muscular dystrophy and their loved ones.

We wish all our readers a happy 2021.