Setbacks and controversies have dogged the search for treatments for Duchenne muscular dystrophy, a degenerative muscle-wasting disorder.
Last week, Pfizer axed its program for the DMD drug Ciffreo, which failed in phase 3.
Sarepta Therapeutic’s drug, Elevidys, the first approved gene therapy for the condition, has had brisk sales of $334 million since the FDA approved it in June 2023 and recently granted it a substantial label expansion. But it’s also beleaguered by controversy such as underwhelming trial data, which raised questions about the efficacy of the treatment that carries a $3.2 million price tag for a single infusion.
There is a bright spot amidst the tumult, however. Capricor Therapeutics, a California-based biotech, recently announced its investigative treatment, deramiocel (CAP-1002), slowed Duchenne progression by almost 50% in patients who had taken the treatment for three years as part of its ongoing phase 2 HOPE-2 open-label extension study, according to Linda Marbán, Capricor’s CEO. Notably, the drug improved heart function in patients who developed an often-fatal form of cardiomyopathy that currently has no approved treatments. Patients in the trial saw a global improvement in ejection fraction, which is the gold standard of cardiac function, she said. And patients with the healthiest hearts at the start of the trial saw the most significant improvement.
The DMD challenge
A gene mutation that triggers a deficit in the muscle-protecting protein dystrophin causes DMD. Because the mutation is on the X chromosome, the disease predominantly affects boys who are usually slower to meet movement milestones than their peers and start to lose abilities around their second or third birthday. The condition also leads to progressive, often fatal, heart and respiratory problems.
The FDA has approved several DMD drugs since 2016 in a market anticipated to reach $18 billion by 2030. Many of them are exon-skipping drugs, which bridge sections of faulty genetic code to help restore some dystrophin protein production.
Regenxbio is also testing a gene therapy, RGX-202, which recently produced positive findings in its ongoing phase 1/2 trial. The treatment appeared to prompt the expression of a shorter but similar version of dystrophin called microdystrophin. Some treated patients saw expression increase as much as 77% compared with controls after three months. It’s not clear, however, if that increase will translate into functional improvements. The company plans to release strength and functional assessment data in the second half of 2024.
Slowing progression
Unlike many of these treatments, Capricor’s phase 3 allogeneic cell therapy doesn’t target the underlying cause of DMD but still aims to slow disease progression. The treatment modulates the immune system to soothe inflammation, reduces fibrosis and helps cells replicate and repair damaged tissues. It could also bolster other therapies and offer an advantage over steroids because it appears to produce few, serious side effects, giving it potential as a long-term treatment.
“One of the best things about this therapeutic is how safe it is,” she said.
Even after multi-year doses, most patients report mild symptoms such as body soreness or headaches following infusions. The treatment, which Marbán said will likely be priced around $1 million a year, similar to exon-skipping drugs, could help keep patients healthier longer.
“We're treating patients that are already on maximal steroid dosing, and we're still seeing additional benefits. We're seeing additional preservation of function, ability to maintain and perform tasks that they either have lost or were in the process of losing,” she said. “That's because with [the] breakdown of the proteins from the cellular destruction you need something to attenuate that inflammation and prevent fibrosis.”
The company is now awaiting phase 3 data for the allogeneic cell therapy, expected at the end of 2024. If all goes as planned, company leaders could apply for a biologics license application by mid-2025, Marbán said. Capricor is also exploring similar conditions that could benefit from the treatment, Marbán said.
“We're looking very closely at Becker muscular dystrophy as our next target,” she said.
The company’s second-generation DMD product, CAP-2003, which Marbán hopes will produce better results than current technology, is in preclinical development.
