Capricor Therapeutics saw its shares fall 13% by the end of trading Monday as its investigational cell therapy deramiocel for DMD was revealed as the first drug expected to face an FDA advisory committee under the new agency’s commissioner, Marty Makary, M.D.
Capricor’s previously announced PDUFA date of August 31 remains, but the biotech said in a release Monday that the FDA is also now asking for an advisory committee (adcomm) to discuss the data for its Duchenne muscular dystrophy (DMD) hopeful deramiocel.
No date has been assigned for the adcomm, though the event will need to occur before the PDUFA date. This is expected to be the first such committee to meet under the auspices of the new Trump administration’s FDA commissioner, Makary.
Shares in the biotech fell more than 13% by the end of trading Monday, likely caused by investor jitters over the drug being the subject of the first adcomm under the Trump administration, as well as the FDA's request for an adcomm in the first place. The FDA can eschew the need for such reviews and sometimes its need for one can be seen as a negative.
Capricor CEO Linda Marbán, Ph.D., for her part, framed the development as progress toward a potential approval.
“The successful completion of our mid-cycle review meeting along with the upcoming advisory committee meeting represents major milestones on the path towards approval of deramiocel,” Marbán said in a statement.
“We have been actively preparing for an advisory committee meeting, and we look forward to providing the physician and patient perspectives to highlight the weight of evidence supporting the transformative potential of deramiocel in treating DMD-cardiomyopathy," Marbán added.
While some Capricor investors appeared caught off guard, the adcomm request is not too surprising. For one, DMD has been a bête noire for the FDA over the years since the controversial approval in 2016 of a Sarepta therapy for the condition.
That drug, Exondys 51, won an FDA thumbs-up nine years ago based on dystrophin production data, but without showing actual clinical benefits such as improvements in disease progression measures. Opinions were split even within the FDA; in fact, two officials who'd opposed the green light decided to retire. In contrast, European regulators shot down Exondys 51 twice around the same period.
In 2019, the agency also gave an accelerated approval to Sarepta’s follow-on DMD drug Vyondys 53, just months after turning it down in what was an unexpected reversal, causing yet more controversy.
Capricor’s drug is a next-gen form of cell therapy in DMD, also likely prompting the FDA to convene its outside committee of experts.
Data for the therapy, which is up for a full approval in patients with DMD cardiomyopathy, come from the biotech’s phase 2 HOPE-2 and HOPE-2 open-label extension (OLE) tests.
Last fall, the latter trial showed that after three years, deramiocel improved DMD patients’ left ventricular ejection fraction and their ability to use their upper limbs.
The trial was small, enrolling just 13 patients, with a deramiocel infusion given every three months. Capricor had previously reported that the treatment met the trial’s main goal in 2021.
There were, however, some safety issues within the trial: All 13 patients in the OLE test experienced a mild to moderate adverse event, with five also experiencing a severe or life-threatening event. Nine of the 13 events were related to the treatment, Capricor reported in its presentation last October.
DMD is a rare genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact. It typically affects boys from a young age and can dramatically reduce life expectancy without treatment.
Deramiocel works as an allogeneic cell therapy of cardiosphere-derived cells, which are connective tissue cells from the heart. The cells secrete tiny cargo packets called exosomes, which target macrophages and alter their behavior so that they become anti-inflammatory and pro-tissue regeneration.
“Deramiocel is a first-in-class cellular therapy with the potential to halt or slow the progression of DMD-cardiomyopathy, and we are pleased to have the opportunity to present the efficacy and safety data to the advisory committee," Marbán said.