Capricor Therapeutics · Nasdaq: CAPR · Deramiocel (CAP-1002)

The 8-K restates the FDA's conclusion almost word for word and describes the CMC items. It does not mention HOPE-2's failed primary endpoint, the post hoc analyses the letter found insufficient, or the cardiac-outcome study the letter recommended.

The letter: “Your BLA does not meet the statutory requirement for substantial evidence of effectiveness” [FDA · Jul 9 · p. 2]. The 8-K says the FDA cited that “the BLA does not meet the statutory requirement for substantial evidence of effectiveness and the need for additional clinical data” [8-K · Jul 11].

The letter's reason is that “The HOPE-2 study failed to demonstrate efficacy for its prespecified primary efficacy endpoint” [FDA · Jul 9 · p. 1] and the post hoc analyses “are not sufficient to provide substantial evidence of effectiveness” [FDA · Jul 9 · p. 1]. The 8-K says the BLA “was supported by data from the HOPE-2 trial, its open-label extension (OLE), and natural history comparisons from FDA-funded datasets” [8-K · Jul 11]. It does not mention HOPE-2's endpoint results, post hoc or exploratory analyses, or multiplicity. [8-K · searched]

The letter recommended a study “whose primary objective is evaluation of cardiac outcomes” [FDA · Jul 9 · p. 2]. The 8-K says the company “plans to submit data from the Phase 3 HOPE-3 clinical trial to provide additional evidence of effectiveness from an adequate and well-controlled study” [8-K · Jul 11]; it does not mention cardiac outcomes or HOPE-3's endpoints. [8-K · searched]

The letter's CMC sections are redacted. The 8-K says they are items “most of which Capricor believes it has addressed in prior communications to the FDA” [8-K · Jul 11], and that “these materials were not reviewed by the FDA due to the timing of the CRL issuance” [8-K · Jul 11]. The letter says “we have stopped the review clock with the issuance of this letter” [FDA · Jul 9 · p. 7]. The CEO is quoted: “We are surprised by this decision by the FDA” [8-K · Jul 11].

The FDA's letter says HOPE-2 failed its prespecified primary efficacy endpoint; Capricor's 10-Q of Nov 10, 2025 says deramiocel met its primary endpoint in HOPE-2 (p=0.01). Neither that 10-Q nor the 10-K mentions the FDA's publication of the letter.

The letter says “The HOPE-2 study failed to demonstrate efficacy for its prespecified primary efficacy endpoint, which was change from baseline to Month 12 in the mid-level (elbow) dimension of the Performance of Upper Limb version 1.2 (PUL 1.2)” [FDA · Jul 9 · p. 1].

Capricor's 10-Q of Nov 10, 2025 says that in HOPE-2 “Deramiocel met its primary endpoint (mid-level PUL v1.2; p=0.01)” [10-Q · Nov 10]; its 10-K says the trial “met its primary efficacy endpoint of the mid-level dimension of the PUL v1.2 (p=0.01)” [10-K · Mar 17].

The 10-Q also says that at the May 2025 mid-cycle meeting “the FDA noted no significant deficiencies” [10-Q · Nov 10], and that the CRL cited CMC items “many of which had been addressed by the Company but were not reviewed prior to issuance of the CRL” [10-Q · Nov 10]. The complaint Capricor filed with its 8-K of May 7, 2026 says “In July 2025, the FDA changed course” [8-K · May 7], and refers to “the absence of deficiencies at mid-cycle review, and more than 50 information requests the FDA had issued and Capricor had answered during the review” [8-K · May 7].

Capricor's 10-Q of Nov 10, 2025 does not mention the FDA's publication of the letter; [10-Q · searched] nor does its 10-K. [10-K · searched] Not in this record: Capricor statements made outside its SEC filings. [not in record]

The FDA's letter of July 9, 2025 says the BLA does not meet the statutory requirement for substantial evidence of effectiveness: HOPE-2 failed its prespecified primary endpoint, and the post hoc cardiac analyses were not sufficient. The letter's CMC sections are redacted in the published version.

The FDA wrote that it “cannot grant final approval because of the deficiencies outlined below” [FDA · Jul 9 · p. 1], having reviewed the submissions “with the exception of the information in the amendments submitted and received on” [FDA · Jul 9 · p. 1] a redacted date.

The first deficiency, under Clinical and Biostatistics: “The HOPE-2 study failed to demonstrate efficacy for its prespecified primary efficacy endpoint” [FDA · Jul 9 · p. 1], “a neuromuscular outcome assessment” [FDA · Jul 9 · p. 1], and the post hoc analyses of HOPE-2 and HOPE-2-OLE “are not sufficient to provide substantial evidence of effectiveness” [FDA · Jul 9 · p. 1]. The letter gives two reasons: HOPE-2 “was not designed to assess effectiveness for the treatment of cardiomyopathy in patients with DMD” [FDA · Jul 9 · p. 1], and its 50 secondary and exploratory endpoints had “no prespecified multiplicity adjustment strategy” [FDA · Jul 9 · p. 2], so “the few nominally significant findings could be spurious” [FDA · Jul 9 · p. 2]. It concludes: “Your BLA does not meet the statutory requirement for substantial evidence of effectiveness” [FDA · Jul 9 · p. 2].

The sections headed Chemistry, Manufacturing, and Controls, Facility and Equipment, and Additional Comments are redacted in the published letter, each marked “(b) (4)” [FDA · Jul 9 · p. 2]; the next item that can be read is “13. We acknowledge receipt of your proposed labeling” [FDA · Jul 9 · p. 7]. The published text does not show whether any redacted item is a comment rather than a deficiency.

The FDA recommended “adequate and well-controlled study(ies), whose primary objective is evaluation of cardiac outcomes in deramiocel-treated patients with DMD cardiomyopathy, compared to a randomized, concurrent control group” [FDA · Jul 9 · p. 2], and said “A resubmission must fully address all the deficiencies listed” [FDA · Jul 9 · p. 7].

The letter asked for a study of cardiac outcomes. HOPE-3 kept upper-limb function as its primary endpoint; the advisory committee voted 3 to 9 that the evidence did not support effectiveness for cardiomyopathy, and Capricor now proposes an indication focused on upper limb function, with an FDA action date of November 22, 2026.

The letter recommended a study “whose primary objective is evaluation of cardiac outcomes” [FDA · Jul 9 · p. 2]. In August 2025 Capricor's 10-Q said “we amended the study protocol to designate LVEF as the primary endpoint” [10-Q · Aug 11]; in November its 10-Q said that after the Type A meeting “The FDA also confirmed that Performance of the Upper Limb (PUL v2.0) should remain the primary efficacy endpoint” [10-Q · Nov 10] and that LVEF is “an appropriate key secondary endpoint” [10-Q · Nov 10].

In March 2026 the company said the FDA “has lifted the previously issued Complete Response Letter and resumed review” [8-K · Mar 10]. In June it said HOPE-3 achieved statistical significance on “the key secondary cardiac endpoint (LVEF)” [8-K · Jun 26]. On July 29 the advisory committee “voted that available evidence did not support the effectiveness of Deramiocel for the treatment of cardiomyopathy in patients with Duchenne muscular dystrophy” [8-K · Jul 30] (“3 for, 9 against, 0 abstain” [8-K · Jul 30]). The August 10-Q says “Under the revised model, LVEF yields a p=0.09 (1.8 percentage point treatment difference), compared to p=0.04 previously reported” [10-Q · Aug 14], and that the FDA issued “a Form 483” [10-Q · Aug 14] citing one observation “in connection with the conduct of the HOPE-3 clinical trial” [10-Q · Aug 14].

On Aug 24, 2026 Capricor said it had asked the FDA to review the data “in support of a refined proposed indication focused on upper limb function, the primary endpoint of HOPE-3” [8-K · Aug 24]; the action date moved “from August 22, 2026 to November 22, 2026” [8-K · Aug 24]. Not in this record: the FDA's advisory committee briefing documents and Capricor's filings after August 24, 2026. [not in record]