CAPR deramiocel

Duchenne muscular dystrophy · Capricor · BLA

Of 100 applications in this same position, about 20 get approved.

Until the FDA deadline48d

Base rate76%

Gap−56pts

PDUFA target date 2026-11-22the FDA may act earlier or later

Summary

FDA approval of deramiocel in this review cycle is put at 20%, far below the 76% base rate for first-time applications from smaller companies. FDA's reviewers found that the pivotal HOPE-3 trial missed its planned primary endpoint (p=0.24) and that the evidence falls short for both heart and upper-limb function; an advisory committee voted 3-9 against on the heart indication and did not vote on upper limb. The company's positive result depends on an analysis plan rewritten after the trial ended. Approval remains possible because the decision now rests on discretion: FDA extended the review to 22 November 2026 instead of rejecting in August, and CBER has new leadership. Manufacturing does not appear to be the obstacle.

Recorded 2026-10-05 00:33 UTC · v1Proof ↓

Evidence · 13 items

Why 20%, not 76%

Indication

Duchenne muscular dystrophy (refined proposed indication focused on upper limb function; originally filed for DMD cardiomyopathy)

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▼ AgainstLarge FDA reviewers say the pivotal trial failed, for upper limb as well as heart

In its briefing document for the 29 July 2026 advisory committee, FDA analysed HOPE-3 under the original analysis plan: the primary endpoint (PUL 2.0 total score) differed by 0.66 points (95% CI -0.45 to 1.77; p=0.24) in a trial powered to detect 1.5 points, and the key secondary endpoint (LVEF) by -0.041 percentage points (p=0.97). The reviewers concluded that the data do "not provide substantial evidence of effectiveness for deramiocel in DMD", that they were "unable to identify a subpopulation that may potentially derive benefit", and that benefit-risk "appears unfavorable". The conclusion covers upper limb function, the indication now under review.

Source: FDA Briefing Document, BLA 125842, advisory committee meeting of 2026-07-29, sections 3.2.4.2-3.2.4.4 and 4: https://www.fda.gov/media/193839/download; FDA presentation, slides 54 and 61: https://www.fda.gov/media/193912/download
02▼ AgainstLarge The company's positive result depends on an analysis plan rewritten after the trial

Capricor reports a significant primary result (4.55 percentage points, p=0.029; published in The Lancet in July 2026). FDA says the plan behind it, version 3.0 dated 24 November 2025, more than five months after the blinded period ended on 18 June 2025 and one day before the data were unblinded on 25 November 2025, "was not submitted to FDA for review" before the filing, and it treats the resulting analyses as post hoc and exploratory. In FDA's re-analysis, version 3.0 as written gives 4.16% (p=0.045); with the original handling of two placebo patients' data it falls to 2.53% (p=0.21). Version 2.0, the last plan sent to FDA (26 September 2025), gives 3.74% (p=0.08) or 2.38% (p=0.26). On 29 July 2026 Capricor itself corrected its LVEF result to p=0.09 (a difference of 1.8 percentage points) from p=0.04 (2.4 percentage points).

Source: FDA Briefing Document, sections 1.3 and 3.2.4.2-3.2.4.3, Tables 3, 7 and 12: https://www.fda.gov/media/193839/download; Capricor 8-K, 2026-07-29: https://www.sec.gov/Archives/edgar/data/1133869/000110465926087891/capr-20260729x8k.htm; Capricor 8-K exhibit 99.1, 2026-08-13: https://www.sec.gov/Archives/edgar/data/1133869/000110465926095908/capr-20260813xex99d1.htm
03▼ AgainstMedium A second review cycle after an efficacy rejection, with no independent confirmation

FDA's complete response letter of 9 July 2025 said the application "does not meet the statutory requirement for substantial evidence of effectiveness". Its request for a controlled study with cardiac outcomes as the primary objective applied if Capricor sought the cardiomyopathy indication; for a general DMD indication FDA had recommended in August 2024 that the application include HOPE-3, and in August 2025 it declined to let Capricor switch HOPE-3's primary endpoint to LVEF. HOPE-3 is therefore the relevant trial for an upper-limb claim, but it stands alone: the earlier HOPE-2 trial (20 patients, stopped early) missed its primary endpoint (2.98 points, p=0.13), and FDA writes that the proposed mechanism is not specific enough to be "biologically plausible as a disease-modifying therapy". The first resubmission (29 December 2025) was ruled incomplete on 13 January 2026. The 76% base rate describes first-time applications.

Source: FDA Complete Response Letter, BL 125842/0, 2025-07-09: https://download.open.fda.gov/crl/CRL_BLA125842_20250709.pdf; FDA Briefing Document, Table 3 and section 3.2.4.6: https://www.fda.gov/media/193839/download; FDA presentation, slide 60: https://www.fda.gov/media/193912/download
04▼ AgainstSmall The advisory committee voted 3-9 against on the heart indication; upper limb was not put to a vote

On 29 July 2026 FDA's Cellular, Tissue and Gene Therapies Advisory Committee voted 3 yes, 9 no, 0 abstain on whether there is substantial evidence that deramiocel is effective for cardiomyopathy in DMD. Upper limb function was a discussion topic without a vote, so the indication now under review has no committee endorsement. Press accounts say members who voted no cited results that were sensitive to the handling of missing data, mainly for LVEF and to a lesser extent for the upper-limb endpoint; one statistician called the results very fragile, and another rated the upper-limb data somewhat better but said he was still not persuaded the product works. Members who voted yes pointed to the upper-limb data. Capricor describes the upper-limb discussion as directionally supportive; that is the company's wording.

Source: Capricor 8-K, 2026-07-30: https://www.sec.gov/Archives/edgar/data/1133869/000110465926088667/capr-20260729x8k.htm; FDA voting question, 2026-07-29: https://www.fda.gov/media/193857/download; FDA discussion topics, 2026-07-29: https://www.fda.gov/media/193913/download; BioSpace, 2026-07-29: https://www.biospace.com/fda/fda-advisers-vote-against-approval-of-capricors-dmd-therapy-in-chaotic-adcomm-meeting; NeurologyLive, 2026-07-29: https://www.neurologylive.com/view/fda-advisory-committee-votes-against-deramiocel-dmd-cardiomyopathy; BioPharma Dive, 2026-07-29: https://www.biopharmadive.com/news/capricor-fda-vote-deramiocel-duchenne-cardiomyopathy/826465/
05▼ AgainstSmall The amendment adds only uncontrolled data

The August amendment adds 24-month open-label extension data and further analyses, not a new randomized comparison. FDA had asked for long-term clinical data on 14 May 2026. Capricor says 82 of the 106 randomized patients reached month 24 (40 originally on deramiocel, 42 on placebo); 101 had completed the blinded year. As reported from a World Muscle Society congress poster on 30 September 2026, patients switched from placebo declined 2.05 PUL points in the blinded year and 0.49 in the open-label year; patients on deramiocel throughout declined 0.95 and then 0.89. FDA has written that PUL scores "may be susceptible to bias" under open-label conditions, and told the committee that post hoc analyses of the earlier open-label study cannot provide substantial evidence of effectiveness.

Source: Capricor 8-K exhibit 99.1, 2026-08-24: https://www.sec.gov/Archives/edgar/data/1133869/000110465926100071/capr-20260824xex99d1.htm; Capricor press release, 2026-09-17: https://www.capricor.com/investors/news-events/press-releases/detail/355/capricor-therapeutics-to-present-hope-3-and-hope-3; Stocktwits report carried by Yahoo Finance, 2026-09-30: https://finance.yahoo.com/markets/stocks/articles/why-did-capr-stock-jump-012424265.html; FDA Briefing Document, sections 2.1.3, 3.2.1.1 and 3.2.2: https://www.fda.gov/media/193839/download; FDA presentation, slide 57 and regulatory-history backup slide: https://www.fda.gov/media/193912/download
06▼ AgainstSmall Doubts about how the trial was run

FDA's briefing says a preliminary review of audit trails found the sponsor departed from its approved blinding plan and moved statistics from an independent vendor to an in-house team in October 2023. It also notes that hypersensitivity reactions in 41.5% of deramiocel patients versus 15.4% on placebo could have revealed treatment assignment. An FDA inspection of the sponsor's clinical operations (6-20 July 2026) ended with a Form 483 with one observation; on 14 August 2026 Capricor said it had responded and was awaiting feedback. FDA's classification of that inspection is not public.

Source: FDA Briefing Document, sections 1.3 and 3.2.4.2: https://www.fda.gov/media/193839/download; Capricor 8-K, 2026-07-29: https://www.sec.gov/Archives/edgar/data/1133869/000110465926087891/capr-20260729x8k.htm; Capricor 10-Q filed 2026-08-14: https://www.sec.gov/Archives/edgar/data/1133869/000110465926097294/capr-20260630x10q.htm
07▼ AgainstSmall Frequent hypersensitivity reactions and a heart-volume signal

In HOPE-3, hypersensitivity reactions occurred in 22 of 53 patients (41.5%) on deramiocel and 8 of 52 (15.4%) on placebo. One placebo patient had a Grade 4 anaphylactic reaction that FDA says may have been caused by the product's excipients. Serious adverse events were fewer on deramiocel (1) than on placebo (5). FDA's analysis also shows the indexed left-ventricular end-diastolic volume rising more on deramiocel (difference 4.78, 95% CI 0.69 to 8.87; nominal p=0.02), and a few committee members reportedly wanted that examined as a possible safety signal. FDA's conclusion is that, given these risks, benefit-risk "appears unfavorable in the absence of evidence of effectiveness".

Source: FDA Briefing Document, section 3.3, Table 11 and section 4: https://www.fda.gov/media/193839/download; FDA presentation, slide 21: https://www.fda.gov/media/193912/download; NeurologyLive, 2026-07-29: https://www.neurologylive.com/view/fda-advisory-committee-votes-against-deramiocel-dmd-cardiomyopathy
08▼ AgainstSmall No sign of labeling talks; the company has turned cautious

In May 2026 Capricor expected labeling discussions to start soon. Its briefing document for the July meeting said they had not yet occurred, and nothing filed since mentions them. On 13 August 2026 it said commercial readiness was advancing more slowly until there is regulatory clarity, put programmes unrelated to deramiocel on hold, and took no questions on its results call, citing the sensitivity of its discussions with FDA. The 10-Q of 14 August says the committee vote is expected to weigh significantly on approvability for cardiomyopathy and that FDA may issue a complete response letter on the amended application. As of 4 October 2026 Capricor has filed no 8-K since 24 August 2026.

Source: Capricor 8-K exhibit 99.1, 2026-05-12: https://www.sec.gov/Archives/edgar/data/1133869/000110465926059380/capr-20260512xex99d1.htm; Capricor 8-K exhibit 99.1, 2026-08-13: https://www.sec.gov/Archives/edgar/data/1133869/000110465926095908/capr-20260813xex99d1.htm; Capricor briefing document, section 1.3: https://www.fda.gov/media/193840/download; Capricor 10-Q filed 2026-08-14: https://www.sec.gov/Archives/edgar/data/1133869/000110465926097294/capr-20260630x10q.htm; Q2 2026 results call transcript, 2026-08-13: https://www.fool.com/earnings/call-transcripts/2026/08/20/capricor-capr-q2-2026-earnings-call-transcript/; SEC EDGAR filing list for Capricor (CIK 1133869)
09▲ SupportsMedium FDA extended the review instead of rejecting in August

FDA did not act on the 22 August 2026 goal date. Capricor's 10-Q of 14 August said FDA had indicated it was willing to review an amendment and, on receipt, to extend the action date; on 24 August the company said FDA had classified the amendment as a major amendment and moved the goal date to 22 November 2026. Capricor says CBER cited the significant unmet need in DMD; no FDA text is public. Under FDA's user-fee commitments, an extension should, "except in rare circumstances", be limited to cases where the new information could lead to approval in the current cycle. Capricor said on 13 August that it was working with FDA on a potential path focused on an upper-limb indication, and the patient group PPMD wrote on 21 August that the review had shifted toward upper-limb function in patients who already have upper-limb impairment. The signal has limits: FDA agreed to extend before the amendment was submitted, and its trial inspection was still unresolved. Only one extension is allowed per cycle, so there is no further formal extension, though FDA can act after a goal date; 22 November 2026 is a Sunday.

Source: Capricor 10-Q filed 2026-08-14 (Next Steps): https://www.sec.gov/Archives/edgar/data/1133869/000110465926097294/capr-20260630x10q.htm; Capricor 8-K exhibit 99.1, 2026-08-24: https://www.sec.gov/Archives/edgar/data/1133869/000110465926100071/capr-20260824xex99d1.htm; PDUFA performance goals FY2023-2027, section I.A.5: https://www.fda.gov/media/151712/download; Q2 2026 results call transcript, 2026-08-13: https://www.fool.com/earnings/call-transcripts/2026/08/20/capricor-capr-q2-2026-earnings-call-transcript/; Parent Project Muscular Dystrophy, 2026-08-21: https://www.parentprojectmd.org/deramiocel-where-we-are-today/
10▲ SupportsMedium CBER has new leadership, and there are precedents for overruling reviewers

Karim Mikhail, acting CBER director from May 2026 and director since 9 September 2026, was also listed as acting head of the reviewing office at the July meeting, where he said the review team had not made a final decision. He has argued publicly for a regulatory framework adapted to rare diseases. In August 2026, according to BioSpace, a senior CBER official overruled a review team that wanted to reject Replimune's melanoma therapy again and it received accelerated approval; a 10-3 favourable committee vote weighed heavily in that decision. FDA has also accepted that existing data for uniQure's Huntington's gene therapy can support an application, reversing an earlier demand for a new trial. In DMD itself, FDA expanded Elevidys in June 2024 although its randomized trial "failed to meet its statistical primary endpoint" and, according to BioPharma Dive, three FDA review teams had recommended rejection. Against this: the negative July briefing was issued while Mikhail already held both posts, and no case was found of the current leadership approving against both its reviewers and a negative committee vote. The director in office at the 2025 rejection left in April 2026.

Source: FDA meeting roster, 2026-07-29: https://www.fda.gov/media/193856/download; Bloomberg Law, 2026-08-10: https://news.bloomberglaw.com/health-law-and-business/rare-disease-drugmakers-watch-fda-for-renewed-focus-on-therapies; BioSpace, 2026-09-03: https://www.biospace.com/fda/replimunes-melanoma-drug-would-have-been-rejected-again-if-not-for-senior-cber-official; BioSpace, 2026-09-21: https://www.biospace.com/fda/mikhail-davis-on-board-with-regulatory-framework-tailored-to-rare-disease-therapies; BioPharm International, 2026-09-09: https://www.biopharminternational.com/view/hhs-names-karim-mikhail-as-cber-director-michael-davis-as-cder-director-in-broader-fda-leadership-shake-up; FDA press release, 2024-06-20: https://www.fda.gov/news-events/press-announcements/fda-expands-approval-gene-therapy-patients-duchenne-muscular-dystrophy; BioPharma Dive, 2024-06-21: https://www.biopharmadive.com/news/peter-marks-fda-sarepta-disagree-rift-elevidys-review/719480/
11▲ SupportsSmall FDA has recently approved drugs after negative committee votes

In 2025 FDA approved Zusduri and Blenrep after negative committee votes, 2 of the 7 meetings held that year; counting 1 rejection after a positive vote, Jefferies found FDA went against its committee in 3 of 7 meetings (43%), against 16% in 2020-2024. In 2026 AstraZeneca's camizestrant received accelerated approval on 4 September, after a committee that did not reach a majority in its favour in April and a goal-date extension announced on 27 May to review additional analyses. The parallel is loose: FDA had requested camizestrant's extra analyses, whereas Capricor proposed its amendment, and in deramiocel's case FDA's own reviewers, not only the committee, dispute that the pivotal trial succeeded.

Source: BioSpace citing Jefferies, 2026-01-06: https://www.biospace.com/fda/fda-went-against-adcomm-votes-more-held-fewer-adcomms-in-2025; AstraZeneca release, 2026-05-27: https://www.astrazeneca.com/media-centre/press-releases/2026/us-fda-decision-date-camizestrant-extended.html; FDA approval notice, 2026-09-04: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-camizestrant-cdk46-inhibitor-esr1-mutated-hr-positive-her2-negative
12▲ SupportsSmall Upper-limb results lean toward the drug, and the unmet need is high

In FDA's own tables the overall upper-limb estimates favour deramiocel without reaching significance on the planned analysis: 0.66 points on the original plan; 0.92 (p=0.11) when the later handling of two placebo patients' data is applied; 0.69 on the mid-level PUL 2.0 score (95% CI 0.007 to 1.36; nominal p=0.048); and 1.75 (p=0.092) in the cohort given product from the commercial site, against -0.09 (p=0.90) in the first cohort. Capricor's absolute-change analysis gives 1.08 points (95% CI 0.00 to 2.16; p=0.0503). FDA treats a change of at least 1 point as clinically relevant. FDA "recognizes the high unmet need for additional safe and effective therapies" in DMD, and after the 2025 rejection it told Capricor (as quoted by the company) that it would "exercise further regulatory flexibility" by reviewing HOPE-3 with PUL as its primary endpoint. Deramiocel holds orphan, rare pediatric disease and RMAT designations. Against this, FDA's opening slides in July 2026 state that the same standard applies to common and rare diseases, and to traditional and accelerated approval.

Source: FDA Briefing Document, Tables 3, 7, 8 and 11, sections 3.2.4.2 and 4: https://www.fda.gov/media/193839/download; Capricor briefing document, sections 1.3 and 6.4: https://www.fda.gov/media/193840/download; FDA introductory slides, slide 11: https://www.fda.gov/media/193913/download
13▲ SupportsSmall Manufacturing does not look like the obstacle

The San Diego plant had its pre-license inspection on 27-30 May 2025, which ended with 5 observations, and Capricor's annual report says FDA accepted all its responses. FDA's July 2026 briefing says its manufacturing reviewers consider product from the earlier Los Angeles facility and from San Diego "to be equivalent", and no manufacturing question was put to the committee. The usual manufacturing risk for a first product therefore looks lower here. The manufacturing and facility sections of the 2025 complete response letter are redacted; Capricor says they held 6 deficiencies and that all were resolved.

Source: FDA Form 483, Capricor, Inc., 2025-05-30: https://www.fda.gov/media/188877/download; Capricor 10-K filed 2026-03-17: https://www.sec.gov/Archives/edgar/data/1133869/000110465926029580/capr-20251231x10k.htm; FDA Briefing Document, notes to Figure 7 and Tables 7 and 8: https://www.fda.gov/media/193839/download; Capricor briefing document, section 4.1: https://www.fda.gov/media/193840/download; FDA Complete Response Letter, 2025-07-09: https://download.open.fda.gov/crl/CRL_BLA125842_20250709.pdf

What would change this forecast

01
Up: Capricor discloses labeling negotiations, an FDA request for a post-marketing or confirmatory study, or any FDA proposal for a conditional route to an upper-limb label.
02
Up: CBER leadership says publicly that the 24-month data or a totality-of-evidence reading supports the upper-limb indication, or approves another therapy against both its reviewers and a negative committee vote.
03
Down: FDA classifies the July 2026 inspection of the HOPE-3 trial as requiring official action, or otherwise questions the reliability of the trial data.
04
Down: Capricor announces a new randomized trial, cuts launch preparation further, or says FDA has asked for additional controlled data.
05
Void rather than no: Capricor withdraws the application before FDA acts.

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

Low

Manufacturing and inspection risk

Low

The commercial plant in San Diego was inspected by FDA on 27-30 May 2025. The 5 observations were: qualification studies that did not reflect actual manufacturing conditions, written procedures not followed, missing quality agreements with outside parties, missing written quality-control procedures for complaints and returns, and equipment in the manufacturing suite not kept in good repair. Capricor says FDA accepted all its responses. FDA's July 2026 briefing says its manufacturing reviewers consider product from the two sites equivalent, and on 12 May 2026 Capricor said it had been able to address all FDA information requests received up to then. What cannot be judged: the 2025 complete response letter contained manufacturing and facility sections (6 deficiencies, per Capricor) that are redacted, and their resolution is stated only by the company. This is also a cell therapy made from donor hearts and the company's first commercial product.

Record · version 1

Written on 2026-10-05, 48 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-05 00:33 UTC 20% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

SHA-25623f61c11ccf3debbe01d84f4f0fb6dc781b3802a2c0fa426e54944d107ad2adc

The fingerprint of the v1 file. It is what the timestamp commits to: change one character of the file and the fingerprint no longer matches.

Verify it yourself

Download the JSON file above and the .ots file of the same name into one folder.
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shasum -a 256 v1_20261005T003307Z.json
ots verify v1_20261005T003307Z.json.ots
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Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-11-20. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.