Duchenne Research Update: February 2017


An Overview of Your Impact in Action

PPMD Grant Awards in the last Quarter of 2016 and first part of 2017.


PPMD Launches Long-Term Gene Transfer Initiative

PPMD has a long history of funding early-stage, innovative preclinical and clinical research for potential therapies. We have kept our eye on gene therapy in Duchenne for a long time, following the earlier challenges with immune reactions and systemic delivery to seeing the current progress that is being made in other disease areas. With this momentum as a back drop, combined with advances in creating functional microdystrophins, we believe we are entering a new chapter in gene transfer therapeutics.


PPMD feels that, while there are still questions to answer about gene transfer therapeutics, the faster we move to answer the questions, the faster we will know if a strategy works. We particularly believe this is true of systemic AAV delivery which can be applied to several gene based therapies.


Early in 2017 PPMD announced two awards as part of our Gene Transfer Initiative:

Our Biggest Grant Ever

The first marked PPMD’s largest single research investment to date, a $2.2 million, milestone driven award to Dr. Jerry Mendell and Dr. Louise Rodino-Klapac of Nationwide Children’s Hospital to conduct a Phase 1 dystrophin gene therapy clinical trial in three patients.

Investing in CRISPR/Cas9

The second was a $250,000 award to Dr. Eric Olson of UT Southwestern to explore CRISPR/Cas9 technology as a potential treatment for Duchenne, including some of the early pre-clinical work to advance the technology and identify any safety risks.


PPMD’s Gene Transfer Initiative is a long-term concept that incorporates Drs. Mendell and Rodino-Klapac’s grant, as well as, the investment into Dr. Olson’s CRISPR/Cas9 work. As with any new research strategy, working together with the entire community to accelerate development is part of our mission and over the next several years other projects and awards related to developing gene transfer therapy will be announced.  We are optimistic that gene therapy will transform Duchenne therapeutics and provide more options for our community.


PPMD Awards $600,000 to NJIT and Talem Technologies for Duchenne Muscular Dystrophy Exoskeleton

PPMD Awards $600,000 Grant to NJIT & Talem

For many people with Duchenne, mobility and function are of utmost importance to quality of life. While drugs are one way to maintain function, the use of robotics and other assistive devices could also greatly impact quality of life. PPMD invested in the New Jersey Institute of Technology (NJIT) and Talem Technologies as a follow-on program to our earlier pilot study exploring the X-Ar exoskeletal arm. In this grant, the arm will be further refined to accept modular robotic assistance technology developed by NJIT. This would be the first of its kind to provide intuitive robotic guidance controls and motorized assistance to people with Duchenne, allowing them to continue to use their arms as their muscles weaken. The team at NJIT and Talem will be initiating a new research study to evaluate the functionality of the refined robotic arms.



A Summary of What Is Going on in Duchenne Research:

Duchenne Pipeline


Deflazacort Approved in the U.S. for Duchenne

On February 9, the FDA approved EMFLAZA™ (deflazacort) for Duchenne. This is the first approval of a steroid for Duchenne and a therapy that applies to people with Duchenne 5 years of age and older, regardless of genetic mutation. Representatives from Marathon Pharmaceuticals joined us for a webinar to provide information about EMFLAZA's FDA-approved label, patient support services, access to this medication, and to respond to questions from our community. On February 13, during the 2017 Advocacy Conference special Forum on Access to Emerging Therapies, Marathon announced that they would be pausing the commercialization of EMFLAZA. This pause will allow Marathon to consider the feedback they have received from the community since last week's announcement regarding pricing and potential for combining this therapy with other approved drugs in the future. Marathon has assured families that during this pause, access to deflazacort will not be disrupted. EMFLAZA's website can help you navigate questions you may have.


Enrolling Commenced

In order to end Duchenne, it will likely take a combination of therapies tackling the disease pathology in various systems. The Duchenne clinical trial pipeline continues to move along, with a number of companies addressing the deleterious impacts of Duchenne from a variety of different angles.


Three studies have started enrolling in the U.S.:


Orphan Drug Designations

Recently our community has seen multiple therapies in development receive orphan drug designation. But what does this mean? According to the FDA website, “The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.


In 2016, two compounds (both supported by PPMD) received orphan drug designation from the FDA:

And in the first weeks of 2017, NS Pharma’s exon 53 antisense oligonucleotide morpholino received orphan drug designation as well. This designation affords certain financial and regulatory advantages for the companies developing compounds for rare diseases.



Catabasis announced top-line results for Part B of the MoveDMD® Trial for Edasalonexent (CAT-1004) in Duchenne. Unfortunately the trial did not meet its primary endpoint, which was to demonstrate a statistically significant decrease in T2 MRI with edasalonexent after 12 weeks compared to placebo in boys affected by Duchenne. MRI T2 measures muscle inflammation.


There were some potential treatment-associated effects at 12 weeks in the 100 mg/kg/day treatment group in both the timed function tests and North Star Ambulatory Assessment when compared to placebo. Therefore, Catabasis will look to see if the signals strengthen in the longer-term data from the ongoing open-label extension.


While we are disappointed in these results, we appreciate Catabasis’ dedication to our community and the families who are participating in this trial. Click here to watch their recent webinar covering this announcement.


FDA Action

PTC’s Translarna received a Refusal to File letter from the FDA. According to the FDA's website, a Refusal to File letter is “an important regulatory tool to help [FDA] avoid unnecessary review of incomplete applications or certain applications that are submitted as an NDA but should have been submitted as an abbreviated new drug application (ANDA).”


PTC, in turn, appealed the Refusal to File letter, but was still denied by the agency. Late in 2016, PTC announced they would file the Translarna New Drug Application (NDA) over protest as this, they feel, is the best path forward to get a full and fair review. They expect to file the NDA in the first quarter of 2017.


Meanwhile in Europe, the Committee for the Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended to renew the conditional marketing authorization based on continued positive benefit-risk assessments from people using Translarna. PTC will be conducting an additional trial of Translarna as a requirement of this renewal.


PPMD remains hopeful that the positive data from studies to date will provide a regulatory path for Translarna’s approval.


Akashi Moves Ahead

It was a sobering day early in 2016 when Akashi’s trial of HT-100 (delayed-release halofuginone), had to be halted due to the death of a participant. And while the cause of death has not been confirmed, it is a sad reminder that trials are still research, although many hope that the unknown benefits are worth the known risks.


Working with the FDA, Akashi recently announced that it is discussing introducing HT-100 back into the clinic in the coming months. There are many details still to work out, but this is a positive sign for many that participated in the earlier trial. Additionally, Akashi has another compound slated to go into the clinic in 2017. This compound is a Selective Androgen Receptor Modulator (SARM) and is intended to increase muscle strength and function. They plan to initiate a double blind randomized proof of concept trial although this trial is not listed on clinctrials.gov at this writing. Akashi also is working on another compound, AT-300, which addresses the calcium level imbalances in muscle which leads to loss of muscle function and cell death.


Akashi is ready to start the studies that need to be done to be granted an IND and allowed to go into the clinic. They hope to start clinical trials by the end of 2017.


This Generation of Clinical Trials

The Duchenne community has worked hard to achieve such a rich pipeline of trials that are in the clinic, many of them supported by PPMD in earlier stages. We need to ensure trials are thorough and efficient, determining viability quickly, so that we don’t waste precious time and resources. While this is not an exhaustive list, it does cover the candidates that are on the horizon.


This Generation of Clinical Trials


Visit PPMD's DuchenneConnect for a comprehensive list of all drugs in development.



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