Top 10 MD Stories of 2021

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by Patricia Inácio, PhD |

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Muscular Dystrophy News Today brought you daily coverage of the latest scientific findings, treatment developments, and clinical trials related to muscular dystrophy (MD) throughout 2021.

We look forward to reporting more news to patients, family members, and caregivers dealing with MD during 2022.

Here are the top 10 most-read articles of 2021, with a brief description of what made them relevant for the MD community.

No. 10 – “CIFFREO Trial of Potential DMD Gene Therapy Delayed in US

In May, Pfizer announced a delay in the start of its Phase 3 clinical trial — called CIFFREO (NCT04281485) — in the U.S. The global trial, to be held at 29 locations, was designed to evaluate the pharmaceutical company’s investigational gene therapy PF-06939926 in boys with Duchenne MD (DMD).

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The delay was caused by questions from the U.S. Food and Drug Administration (FDA), specifically regarding Pfizer’s potency tests, which are used to measure the therapy’s ability to elicit a specific response at a selected dose.

The company announced it was working to address the FDA’s concerns. In the meantime, the trial continued recruiting at its other clinical sites, located in the U.K., Italy, Spain, Israel, South Korea, Japan, and Russia.

PF-06939926, which now has the approved generic name fordadistrogene movaparvovec, is a gene therapy that uses a harmless, modified adeno-associated virus (AAV) as a vehicle to deliver a mini-dystrophin gene into muscle. As its name suggests, mini-dystrophin is a shortened, though functional version of the dystrophin protein and is expected to slow or halt the muscle degeneration of DMD.

No. 9 – “Sarepta Acquires Investigational Gene Therapy for LGMD2A

In early August, Sarepta Therapeutics entered an exclusive license agreement to develop a gene therapy candidate, called calpain 3 or CAPN-3, that’s designed to treat limb-girdle muscular dystrophy type 2A (LGMD2A), the most common form of LGMD.

The agreement with the Abigail Wexner Research Institute at Nationwide Children’s Hospital, in Columbus, Ohio — the therapy’s developer — followed a number of successful preclinical and safety studies.

The gene therapy was designed to deliver a healthy version of the CAPN3 gene to skeletal muscle tissue. Mutations in that gene are the cause of LGMD2A.

AAV, the viral vector used in this gene therapy, also is being used in Sarepta’s potential approaches for DMD, including its lead candidate in that indication, SRP-9001.

No. 8 – “Exon Skipping Dominates DMD Treatment, But What’s on Horizon?

Our eighth most-read article of 2021 explains the science and benefits of the four exon-skipping therapies available in the U.S. for eligible DMD patients. These are Amondys 45 (casimersen), Exondys 51 (eteplirsen), and Vyondys 53 (golodirsen), all by Sarepta, and Nippon Shinyaku’s Viltepso (viltolarsen). All of these therapies were approved from 2016 onward and, combined, are able to treat nearly 30% of all DMD cases.

This story also discusses the science and potential of another type of disease-modifying therapy, called stop codon readthrough. One such therapy, called Translarna (ataluren), is being developed and marketed by PTC Therapeutics.

More information about the most advanced gene therapies, Pfizer’s PF-06939926 and Sarepta’s SRP-9001, also was presented.

No. 7 – “Pivotal Trial of DMD Gene Therapy SRP-9001 Launches Globally

Sarepta Therapeutics and Roche jointly launched a pivotal clinical trial, called EMBARK, in October to test Sarepta’s investigational gene therapy SRP-9001 in boys, ages 4 to 7, with DMD.

The trial, planned for clinical sites in the U.S., Europe, and Asia, was designed to evaluate the safety and effectiveness of SRP-9001. Its main goal is to assess how the gene therapy affects patient scores on the North Star Ambulatory Assessment, a measure of motor abilities in individuals with DMD who are able to walk.

SRP-9001 uses a harmless virus to deliver the gene encoding micro-dystrophin directly to muscle cells.

No. 6 – “Sustained Gains for DMD Boys Evident in SRP-9001 Trials: Sarepta

Shortly after the announcement of EMBARK’s launch, Sarepta released data from several trials of SRP-9001 that show the gene therapy leads to sustained functional improvements in DMD patients, while maintaining good tolerability.

Data from a proof-of-concept Phase 1/2 trial, called Study 101 (NCT03375164), involved four boys with DMD, ages 4–7 at enrollment. These boys showed an improvement of 8.6 points in the North Star Ambulatory Assessment (NSAA) total scores over three years following a single infusion of SRP-9001, when compared with a matched control group whose members did not receive the therapy.

In the follow-up Phase 2 trial, called Study 102 (NCT03769116), 41 boys with DMD, ages 6 and 7, were given SRP-9001. As compared with a control group, these boys showed an improvement of 2.9 points compared with the start of the trial (baseline) at 48 weeks (around 11 months).

The open-label Phase 1 ENDEAVOR trial (NCT04626674), being conducted with Roche, assessed SRP-9001 in 32 DMD patients: 20 boys, ages 4–7, and 12 older patients, both ambulatory (able to walk) and non-ambulatory.

Data from the first 11 boys treated showed a significant 3.0-point improvement in NSAA scores at six months, compared with their pre-treatment scores.

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No. 5 – “Benefits Seen With Losmapimod ‘First’ for FSHD Trial, Fulcrum Says

Fulcrum Therapeutics acknowledged in June that losmapimod, its candidate oral treatment for facioscapulohumeral muscular dystrophy (FSHD), failed to reach its main goal in a Phase 2b trial.

However, in an interview with Muscular Dystrophy News Today in August, the company viewed this as a constructive failure — and as a way to shape losmapimod’s continued advancement. The therapy’s development is supported by the secondary trial goals, and by clinically relevant benefits, seen in comparison with a placebo after almost a year of treatment, the company said.

The main goal of the ReDUX4 trial (NCT04003974) was to measure changes in the activity of the DUX4 gene, whose aberrant activity causes FSHD in more than 90% of all patients.

While losmapimod failed to significantly reduce DUX4-driven gene activity, it led to clinically relevant improvements in secondary measures after 48 weeks (just shy of one year), including changes in muscle fat infiltration, and reachable workspace. Reachable workspace is a measure of the range of motion a person has in their arms and hands.

No. 4 – “#MDA2021 — Gene Therapy for DMD Exon Duplication Showing Promise in Trial

This fourth-most-read story of 2021 reported on an experimental exon skipping gene therapy from Astellas Gene Therapies, formerly Audentes Therapeutics, which was found safe and effective at increasing dystrophin levels and stabilizing muscle function in DMD patients with exon duplications.

The six-month data from the first two treated boys in a Phase 1/2 clinical trial (NCT04240314) were presented at the 2021 MDA Virtual Clinical and Scientific Conference, held online in March.

Exons are sections of genetic information needed to make proteins. Exon duplications account for nearly 11% of cases of DMD or other conditions characterized by dystrophin deficiency. The most common DMD-causing mutations involve the deletion of one or more exons.

These findings represent the first evidence of full-length dystrophin protein production following gene therapy, and support further testing of the treatment in younger patients and at higher doses.

No. 3 – “#MDA2021 – DMD Gene Therapy PF-06939926 Continues to Show Promise

Pfizer’s investigational gene therapy PF-06939926 continued to show an acceptable safety profile and the potential for substantial benefits in motor function in DMD boys, according to data from a Phase 1b clinical trial (NCT03362502).

The company presented the NSAA scores from three boys given a low-dose — 1E14 vector genomes (vg)/kg — and three given a high-dose of 2E14 vg/kg.

Compared with a control group of DMD patients who had received a placebo during previous clinical trials, two patients in the low-dose group and all three high-dose patients showed higher or at least no decline in NSAA scores.

Of note, this trial was paused late in 2021 due to the death of a participant, although the cause was still to be determined at year’s end.

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No. 2 – “FDA Approves Amondys 45 for Duchenne Patients Amenable to Exon 45 Skipping

Early in the year, the FDA announced the conditional approval of Sarepta’s Amondys 45 (casimersen) as the first treatment for DMD patients amenable to exon 45 skipping.

Conditional approval is granted to a medication whose immediate availability fulfills an unmet medical need, provided early evidence shows that its benefits outweigh potential risks.

The FDA’s decision was based on preliminary data from the ongoing Phase 3 ESSENCE study (NCT02500381), which is evaluating the therapy’s safety and effectiveness in people with DMD-causing mutations amenable to exon 45 skipping.

That preliminary trial data came from the trial’s first 43 participants: patients ages 7 to 20, of whom 27 were assigned to receive Amondys 45 and 16 a placebo. After 48 weeks, or just shy of one year, those given the treatment were found to have experienced a significant increase in dystrophin levels in muscle biopsies, compared both with the levels at the start of the trial and with those given a placebo.

No. 1 – “Dosing Begins in Phase 3 Trial of Pfizer’s Gene Therapy for Duchenne

Our most-read article of 2021 concerned the dosing of a first DMD boy, in January, in the Phase 3 trial testing Pfizer’s gene therapy, PF-06939926.

The CIFFREO trial’s enrollment target is 99 boys with DMD, ages 4 to 7, who are able to walk independently. Its primary goal is to assess changes in NSAA scores one year after treatment.

PF-06939926 received fast track status from the FDA based on its positive results in a Phase 1b trial involving boys and men with DMD. Such results included the sustained production of the mini-dystrophin protein in muscle tissues and motor function improvements.

Fast track status helps to speed clinical development and regulatory review, and eases market entry upon approval for treatments with the potential to address serious conditions.

Our reporting on a delay in the start of this trial in the U.S. was the 10th most-read story of 2021, as noted earlier.


At Muscular Dystrophy News Todaywe hope these stories and our reporting throughout 2022 contribute to informing and improving the lives of everyone affected by MD.

We wish all our readers a happy 2022.