Capricor Posts Bytreldo CRL Response

Capricor Therapeutics says it is posting on its Web site the company’s “comprehensive preliminary response” to an FDA complete response letter (CRL) for the BLA for Bytreldo (deramiocel), an investigational cell therapy intended to treat cardiomyopathy associated with Duchenne muscular dystrophy (DMD). While acknowledging in a statement FDA’s public announcement that it intended to publish publicly all CRLs when they are issued to sponsors, Capricor says it was not notified in advance that the CRL would be posted, and says the agency did not also release the company’s response.

In its response, the company says FDA cited one clinical and biostatistical deficiency; six chemistry, manufacturing, and controls deficiencies; and six additional comments. Capricor challenges FDA’s interpretation of some of the deficiencies and explains how others were being addressed at the time of the CRL.

It also says that the BLA was prepared “based on feedback from FDA’s cardiology review team and with full transparency of its intentions. It is difficult to understand the massive changes in the agency’s feedback provided in the CRL, when the initial plan to use the HOPE-2 and HOPE-2 OLE [trials] as the clinical basis for the BLA was set into motion with FDA’s agreement just under one year ago. The events that have transpired up to this point are inexplicable and unprecedented.”

In a concurrent open letter to the DMD community posted with the response, Capricor says the CRL “came as a surprise to us, particularly given prior discussions with the agency that encouraged us to proceed with our submission based on data from our HOPE-2 and HOPE-2 OLE studies. While we respectfully disagree with FDA’s interpretation of these data, we are fortunate to already have a Phase 3 clinical trial (HOPE-3) underway. We plan to propose including data from this pivotal study to strengthen and seek to amend the current BLA in support of the cardiomyopathy indication.”

In its statement, Capricor says its written response provided clarifications to the agency’s feedback and outlined its proposed plan to address the outstanding issues. “To ensure transparency,” it says, “Capricor will make its preliminary response available on the investor section of its Web site for patients, families, and other stakeholders to review.”

Company officials are quoted as saying that transparency is vital in regulatory communications, and while Capricor respects FDA’s process, the company believes it is important that the public has visibility into both the CRL and the company’s detailed written response that was submitted to the agency.

Bytreldo is described as allogenic cardiosphere-derived cells that have been shown in preclinical and clinical studies to exert potent immunomodulatory and anti-fibrotic action in the preservation of cardiac and skeletal muscle function in dystrophiopathies such as DMD. It has received FDA orphan drug designation to treat DMD, regenerative medical advanced therapy designation, and rare pediatric disease designation.