Championing Charley’s Cause

Aug 25, 2014

Championing Charley’s Cause

By Meaghan Casey

For Dr. Benjamin Seckler and his wife, Tracy, the decision to become influential players in the biotech world was driven by one goal: to save their child’s life.

“Nothing can motivate you more than racing against the clock,” said Seckler.

Their 13-year-old son, Charley, is battling Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration and weakness. Children with DMD cannot produce dystrophin, a protein necessary for muscle strength and function. As a result, every muscle in the body deteriorates. Skeletal muscle deteriorates first and respiratory and heart failure follows, often by the time patients are in their late teens or 20s.

Although Duchenne is the most common fatal genetic disorder to affect children, there is no cure.

“We’re in business to go out of business,” Seckler said. “The end game is to cure or convert this rapidly fatal disease into a chronic, manageable illness.”

Charley was 3½ when he was diagnosed with DMD. Seckler described his muscular tone as loose, and as Charley got older he had delayed milestones when walking and balancing. A visit to the neurologist confirmed he had elevated levels of creatine kinase, an enzyme that leaks out of damaged muscle.

“With one blood test, our whole lives changed,” said Seckler. “Almost immediately, we revved into high gear on two fronts: getting Charley the best possible medical care and finding a cure in time to save his life. It didn’t take long for us to come to the conclusion that we needed to start a foundation to expedite research and a cure.”

Charley’s Fund was born four months later, with a sole mission of funding a cure or treatment for Duchenne. The foundation invests its money in translational research – research that focuses on moving science from the lab into human clinical trials. To date, the foundation has directed more than $25 million to support that research.

Once Charley’s Fund was established, Seckler, a physician and radiologist, took the next step and launched DART Therapeutics to develop new therapeutics to treat DMD. On June 24, the Cambridge-based company was renamed Akashi Therapeutics, merging the operations of DART and its subsidiary Halo Therapeutics into a single entity.

“Akashi  is a novel partnership between biotechnology  veterans and patient organizations combining industry expertise with focus and urgency to expedite drug development and access to innovative medicines,” said Seckler. 

The company has received fast track FDA status for its lead drug candidate, HT-100 (delayed-release halofuginone), an orally available, small molecule drug candidate intended to reduce fibrosis and inflammation and promote healthy muscle regeneration in boys with DMD. It is enrolling and dosing DMD patients in an ongoing clinical study to evaluate the safety and tolerability of increasing doses of HT-100, and explore trends in a range of efficacy endpoints. Preliminary clinical data on the first patient cohorts in the study were presented at the 2014 New Directions in Biology and Disease of Skeletal Muscle Conference, which was held June 29 to July 2.

Last summer, Charley and 11 other patients received their first dose of HT-100. Charley went back again this July for a second dose. Seckler said the drug has been well tolerated.

“When we acquired the drug, we reformulated it with a coating and delayed release so that it isn’t broken down in the stomach, and there are no side effects,” said Seckler.                                    

Designed to decrease the dystrophy, or the inflammation and fibrosis, HT-100 also promotes muscle fiber regeneration.  Seckler describes it as a “mini cocktail,” targeting three pathways of the disease.

“It’s going to be an essential ingredient in the ultimate cocktail that will treat these patients,” said Seckler. “The holy grail – gene replacement therapy – is still several years away, at least. The strategy in the meantime is to keep these muscles as healthy as possible.”

Also in Akashi’s pipeline is DT-200, an oral SARM (selective androgen receptor modulator) with positive phase 1 clinical data that has broad potential for multiple neuromuscular diseases. The next step in development is to assess the effects of DT-200 in increasing muscle mass, strength and motor function in healthy volunteers. Successful outcomes in this clinical trial will lead to further development in DMD or other neuromuscular disorders.

“Right now, the mission is to do what we did with HT-100—find another diamond in the rough,” said Seckler.

Much of their progress has been possible because of the Food and Drug Administration Safety and Innovation Act (FDASIA), signed into law on July 9, 2012, which expanded the FDA’s authorities and strengthened the agency’s ability to expedite patient-driven therapies for rare diseases.

“Congress understands we need to change the way we develop treatments,” said Seckler. “In this case, DMD is the poster child, Charley’s Fund is the engine and Akashi is the vehicle. We just need the medical science to fuel us to the finish line.” 

See all MassBio News