The cell therapy biotech Capricor recently released new data from their Duchenne Muscular Dystrophy (DMD) trial work. The data have generated excitement in the patient advocacy community. The stock has skyrocketed.
How exciting are these new data?
CEO Linda Marbán is quite upbeat and I think it’s justified.
The firm is now seeking FDA approval for its stromal cell product deramiocel.
Deramiocel data
I finally got a chance to look at the newest Capricor Duchenne data from an extension of their HOPE-2 trial or “Halt cardiomyOPathy progrEssion in Duchenne (HOPE-OLE) (HOPE-OLE).”
Overall, these new data are solid and encouraging. More specifically, Deramiocel is associated with cardiac and skeletal muscle improvements in participants with DMD, while in general untreated patients tend (from unrelated clinical data) to get much worse.
From an optimistic view, an FDA approval before the end of 2025 seems possible. Note that the agency granted Sarepta approval for their Duchenne gene therapy even with mixed data.
Encouraging development for Capricor
Capricor’s new data builds on their 2022 Lancet paper from the HOPE-2 trial: Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.
In the new OLE data, clinical trial participants who received deramiocel fared significantly better including in terms of heart function than expected outcomes based on independent comparator data. Using the comparator data is not as robust as a comparison to a placebo control group, but its standard for an OLE or open-label extension, which typically drops placebo controls and makes the investigational drug available to all participants.
From Capricor CEO Linda Marbán:
“The results of the open-label study are tremendously important for DMD patients, as they showed sustained skeletal and cardiac benefits after three years of continuous treatment with deramiocel, which underscores the potential long-term benefits this therapy can offer patients with DMD.”
It’s worth noting that some adverse events include grade 3 events were common in recipients in the trial, but the benefits may outweigh the risks.
Possible deramiocel mechanisms
How would likely transient presence of a donor cardiosphere product product a meaningful, lasting benefit? What’s the mechanism? The firm says the product secreted beneficial exosomes or extracellular vesicles. In turn, immunomodulation by these exosomes is thought to be a key mechanism.
In thinking more about possible mechanisms, what exactly is CAP-1002 or deramiocel? The firm defined it in their paper this way:
“Cardiosphere-derived cells (CDCs) are a type of stromal or progenitor cell, which target macrophages and alter their expression profile so that they adopt a healing, rather than a pro-inflammatory, phenotype. Exosomes secreted by CDCs also reprogramme fibroblasts, rendering them antifibrotic.”
If this mechanism holds up, there’s a beautiful, useful irony in fibroblasts having an antifibrotic effect.
This sounds a lot like the possible mechanisms invoked by advocates of the use of MSCs for various conditions. The firm used that key word “stromal” in the above quote as well, which kind of invokes cardiac fibroblasts or MSC-like stromal cells.
The fact that cardiac stromal cells, especially allogeneic ones, are probably not going to engraft in a meaningful way, explains the need for continuous infusion.
What will the FDA do?
I highly recommend Adam Feuerstein’s piece over at STAT News on this new Capricor data including insights related to the FDA and the agency’s decision on Sarepta. From the piece:
“In the short term, deramiocel can preserve cardiac function,” said Marbán. “From a long-term perspective, we are hoping and anticipating to see a mortality benefit.”
Adam also wrote about the new Phase 3 trial:
“That study, called HOPE-3, is underway, but Capricor also continued to monitor the heart function of participants in an open-label extension of the HOPE-2 study. After three years, an analysis showed continued and widening improvement in cardiac function favoring deramiocel compared to data from a separate “natural history” study of heart function in Duchenne patients.”
A key question is whether the FDA’s CBER branch will approve deramiocel in 2025 without HOPE-3 data or other longer-term data.
I wouldn’t be surprised if we see an FDA approval for deramiocel in 2025 but it’s probably a coin toss at this point. It would be no shocker if the FDA wanted more data, but CBER Director Peter Marks seems more inclined to approve some types of products the last few years.
I hope the data continue to look strong and Capricor gets its deramiocel approval.
Notes
- Note that Craig McDonald, the lead scientist for much of this work, is my colleague here at UC Davis and Shriners, but I was not involved in the research.
- I also have no financial interests in Capricor or any other cell therapy firms at this time.
- This post is not financial advice.