ORLANDO, Florida—In 2003, Paul and Debra Miller of Newport Beach, California, founded the nonprofit group CureDuchenne after doctors diagnosed their son, Hawken, with Duchenne muscular dystrophy (DMD).

Nearly 2 decades later, the Millers still haven’t achieved their goal: namely, to “cure Duchenne.”

However, speakers at the group’s recent annual conference here say they’re closer than ever.

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“Debra and I did not sign up for this almost 20 years ago, but when we found out Hawken had Duchenne, we knew we had to do something,” Paul told participants at CureDuchenne’s 2022 Futures gathering in May. “This is exactly what we thought it would turn out to be—and it’s been an amazing journey.”

Mindy Cameron of Carmel, Indiana, also has a son with the disease.

“I live with Duchenne every day, like most of you in this room, and I remember when there were no clinical trials,” said Cameron, patient advocacy lead at Santhera Pharmaceuticals. “Besides a cure, all we’ve really been working for are more options, where there are several therapies available. And the more options we have, the more physicians would welcome opportunities to assess each individual boy.”

Michael Kelly, MD, chief scientific officer at CureDuchenne since 2011, said his organization has long made it a point to forge deep relationships with leading biotech and drug firms, bringing its years of expertise to help them accelerate their own research.

“Where we are today is the culmination of a decade’s worth of priming the pump, so to speak,” Dr. Kelly told Rare Disease Advisor. “We’ve certainly seen our share of failures, because drug development is inherently risky, but I think today we can look forward to some therapies that look as if they’re going to be quite transformative.”

Five FDA-Approved Therapies

A great example of that, he said, is exon skipping.

“The first drugs that were approved, a handful of years ago, had severe limitations in use and efficacy, and that brought around new technologies that have driven innovation in that. Today, we’re seeing Sarepta Therapeutics with their [peptide phosphorodiamidate morpholino oligomer (PPMO)] cell‑penetrating oligonucleotide exon‑skipping drugs that are in late‑stage clinical development,” he said.

“Then closely tied in behind that, there’s a handful of other companies like Dyne, Avidity, and others that are accelerating new technologies in order to focus and make exon skipping not only more directed towards muscle, but much more efficient in general.”

Mike Kelly, MD
Michael Kelly, MD, chief scientific officer at CureDuchenne. Credit: Larry Luxner

To date, CureDuchenne says it has leveraged more than $2.3 billion in investment from venture capital, biotech, and pharmaceutical companies to fund research. In addition, the organization has funded 44 research projects, 16 of which have advanced to human clinical trials. The charity also contributed early funding to Sarepta, the first company to have a Duchenne therapy approved by the US Food and Drug Administration (FDA).

That drug was eteplirsen (Exondys 51), a once-a-week infusion that benefits the 13% of Duchenne patients with exon 51 mutations. Since then, 4 other therapies have received the FDA’s blessing: Sarepta’s casimersen (Amondys 45TM ) and golodirsen (Vyondys 53 TM ); NS Pharma’s viltolarsen (Viltepso®); and PTC Therapeutics’ deflazacort (Emflaza®).

“We have a real major focus on drug development, and that those investments that we make, if successful—and we have been extremely successful at it—have fed money back into the system, so it’s almost a self‑propelled organization,” Dr. Kelly said.

“You have to remember that science and business is hard‑linked and hard‑wired together. Success and science will lead to investors actually making money, and at the end of the day, patients will benefit from all of that. If we make mistakes and there’s no return on investment, there’s no upside for our patients.”

For this reason, he said, “we tend to focus on companies where the amount of money that we can put in, along with our expertise, can either help de‑risk a platform or accelerate it.”

‘Transformative’ Advancements on the Horizon

In 2016, CureDuchenne funded Bamboo Therapeutics to advance early-stage gene therapy research. Bamboo was later acquired for $154 million by Pfizer, which began a phase 3 investigational gene therapy trial in 2020 and is now recruiting patients. And in 2017, CureDuchenne helped finance Exonics Therapeutics, which did pioneering work with CRISPR Cas9 gene editing technology; that company has since been acquired by Vertex.

Yet “despite having 5 FDA-approved treatments for Duchenne, there’s still quite a lot of work to do,” said Han Phan, PhD, a principal investigator at Rare Disease Research in Atlanta, Georgia. “As we approach the right treatment for DMD, there are multiple targeted areas that would be effective. It all starts with the mutations of the dystrophin gene.”

One of the group’s most innovative projects is CureDuchenne Link, launched in June 2021. Basically, it’s a neutral, independent biobank open to anyone with Duchenne or Becker muscular dystrophy that aims to help scientists discover new treatments.

Blood samples are taken twice a year from those with Duchenne, and once a year from carriers, while urine, saliva, skin, and muscle samples are taken once per year from both groups. Participants also answer annual surveys on quality of life, healthcare usage, and other topics.

“In clinical research, everybody’s trying to keep things to themselves,” said Heather Medlin, the organization’s senior director of clinical operations. “Families and individuals are asked all the time to participate because they have a certain mutation. But only a small percentage of the blood samples they donate is actually used. So what we say is, ‘let’s have a central repository where it’s not owned by anybody but for the good of all research, where everyone could access it.’”

Medlin, a clinical researcher based in Raleigh, North Carolina, has spent over 20 years in research, observational studies, and registries. She said her goal is to have 5000 people in the database, and to “gather quality data and biosamples from as large and diverse a population as possible, to create one accessible resource in order to accelerate research toward a cure.”

Dr. Kelly, who had a 30-year career with Pfizer, GlaxoSmithKline, and Amgen before joining CureDuchenne in 2011, predicted that a gene therapy for Duchenne could win FDA approval “perhaps as early next year,” and that when it happens, it will be “transformative” for a significant subset of DMD patients.

“I think the vast majority of projects will fail to cross over the final line. That’s the nature of drug development,” he said. “But each one of those projects that don’t make it teach us a tremendous amount about what’s wrong. Failures are important, because that’s how we actually learn to modify and improve.”