Until recently, most people with Duchenne muscular dystrophy (DMD) only lived into their teens. But drugs, including steroids and advances in heart and respiratory therapy, have slowly pushed the needle on life expectancy for people with the devastating genetic disorder into their 30s, sometimes beyond.
Capricor Therapeutics, a California-based biotechnology company is hoping to add another tool to the growing arsenal of treatments for DMD with its phase 3 allogenic cell therapy, CAP-1002.
“It works in a similar fashion as a CAR-T (cell therapy) might, which is in the modulation of the immune system. So, it's actually calming down inflammation, reducing fibrosis, allowing cells to replicate and to drive repair,” Capricor CEO Linda Marbán, said.
While CAP-1002 is not a cure for the underlying disease, it aims to slow disease progression.
For patients with DMD, which causes muscles to slowly waste away, the mutated DMD gene is located on the X-chromosome so the disease predominantly affects boys. People with DMD are usually slower to sit, stand and walk than their peers, and start to show progressive signs of the disease around their second or third birthday.
A phase 2 trial of CAP-1002 found that the cell therapy was able to slow down muscle deterioration in patients with late-stage DMD by 71% over 12 months compared with a placebo.
“We consider our cell therapy to be one of the most important opportunities for Duchenne patients."
Linda Marbán
CEO, Capricor Therapeutics
“It basically takes a two-year decline in a typical patient and turns it into a less than one year decline, about nine months,” Marbán said. “So, you are seeing a very significant delay.”
Unlike steroid medications, which are also used to slow DMD disease progression, CAP-1002 appears to have fewer serious side effects. Only one person in the phase 2 trial had to discontinue the drug due to an allergic reaction, but there were no other serious problems reported. Slowing the rate of decline can offer hope for DMD patients.
“It's just like with oncology, every day you're alive, there's one more chance to get a better therapy,” she said.
A burgeoning market
Drugmakers have triggered a surge in new treatments for DMD in recent years and the global market for DMD drugs is anticipated to grow from $1.1 billion in 2022 to $18 billion in 2030.
Since 2016, the FDA has approved several DMD drugs, many of them in a category called exon skipping drugs, which help the body to resume some dystrophin protein production. The drugs are essentially able to create a bridge over faulty exons, or sections of the genetic code used to make protein, to link healthy sections. The drugs in this category, all approved by the FDA under its accelerated approval pathway, include three therapies from Sarepta Therapeutics and one from NS Pharma.
Other treatments are also being explored, such as gene repair and gene therapy. In a narrow eight to six vote, an FDA advisory committee recently recommended approval of the first gene therapy, SRP-9001, from Sarepta. Based on the advisory board recommendation, the FDA could approve the treatment using its accelerated pathway by the end of May.
Another treatment called ataluren is being tested through a partnership between PTC Therapeutics and Genzyme, and aims to overcome a stop codon in the middle of a gene sequence that interferes with protein production.
Marbán said CAP-1002 could play a valuable role even amidst other emerging treatments.
“We consider our cell therapy to be one of the most important opportunities for Duchenne patients, because no matter what disease-modifying or dystrophin modifying technologies come to bear, CAP-1002 will be a good partner for those therapies. That’s why we call it a backbone therapy in our own vernacular,” Marbán said. “There is nothing that does as good of a job at calming inflammation and driving muscles into endogenous repair as CAP-1002, at least as has been evidenced in current clinical trials.”
Capricor is currently enrolling patients in its phase 3 trial. If all goes well, Marbán said they hope to apply for a biologics license application and ask the FDA for approval by mid-2025.
“That seems like tomorrow and a long time in the future all at the same time,” she said.
