In May 2020, Capricor Therapeutics reported that the US FDA approved the Investigational New Drug (IND) application for an expanded access program to investigate the use of CAP 1002 in 20 additional patients with COVID-2019 infections. The IND was submitted in April 2020, based on the data from the six patients enrolled in the compassionate programme initiated by Capricor Therapeutics to provide CAP 1002, to patients with advanced COVID-19 under the compassionate use pathway (NCT04338347). The company released the results in April 2020     .
In October 2016, Medical University of South Carolina initiated a feasibility phase IIa trial to assess the exploratory efficacy and safety of CAP 1002 intracoronary infusion in patients with heart failure with preserved ejection fraction (54823; NCT02941705). The efficacy endpoints will determine if CAP 1002 treatment affects clinical functional status (QOL scores), exercise tolerance (6 Minute Walk Test - 6MWT), exercise haemodynamics (supine exercise ergometry during right heart catheterisation), myocardial interstitial fibrosis (MRI with native T1 mapping and calculation of extracellular volume after gadolinium administration), macroscopic fibrosis by delayed gadolinium enhancement and diastolic function (catheterisation, echocardiography, BNP). The randomised, double-blind, parallel, placebo-controlled trial recruited 40 patients in the US  .
In April 2019, Capricor ceased the ongoing follow-up activities and terminated the ALLSTAR trial to focus resourcing on its active HOPE-2 trial. The Clinical data obtained from the phase I/II ALLSTAR trial showed lack of a clear difference in the change in scar size from baseline to six months between the active and control groups (1002-01; RC3HL103356-01; NCT01458405)  . The enrolment of 134 patients with myocardial infarction in the randomised, double-blind and placebo-controlled trial was completed in the US and Canada, in October 2016. The stem cells were delivered intracoronarily into a single coronary vessel, and the infarct size was assessed by MRI. ALLSTAR assessed the use of intracoronary CAP 1002 from 30 days to one year post-myocardial infarction. The study was intended as a proof-of-concept trial to validate the results of CADUCEUS trial from the CAP 1001 drug programme [see Adis insight drug profile 800034783] using an allogeneic product and simultaneously looking for efficacy in patients. The trial consisted of a 14-patient lead-in phase, and an additional enrolment of patients in the phase II portion. The trial was initiated in October 2012     . In December 2013, Capricor received notification from the National Heart Lung and Blood Institute (NHLBI) Gene and Cell Therapy (GST) Data Safety Monitoring Board (DSMB) that the phase I portion met its safety endpoints, and that the company initiated the phase II portion  . Capricor Therapeutics and the ALLSTAR DSMB decided to reduce the enrolment goal of the phase II portion from 300 to 120 patients, based on the statistical results, in March 2016  . Positive phase I data were reported in March, July, September and November 2014     . The phase I portion of ALLSTAR was partly funded by a grant from the National Institutes of Health, and the phase II portion is partly funded by the California Institute for Regenerative Medicine (CIRM)of $US3 millions     .
Capricor has initiated the phase Ia/Ib DYNAMIC (Dilated cardiomYopathy iNtervention with Allogeneic MyocardIally-regenerative Cells) trial to assess CAP 1002 in patients with advanced heart failure (CAP1002DYNAMIC; R44HL095203-04; NCT02293603). In January 2015, the company announced that the first three patients were administered with CAP 1002, through non-occlusive intracoronary infusion via 3 vessels, in the NIH-sponsored DYNAMIC trial, in the US. The phase Ia portion is an open-label, single centre study evaluating the safety of CAP 1002 in 14 patients. As at April 2015, enrolment was completed. The trial has been funded in part through a $US3 million National Institute of Health grant  . The phase Ib portion of the study is designed as a randomised, double-blind, placebo-controlled study, and will evaluate the safety and efficacy of CAP 1002 in 28 patients at up to four sites. CAP 1002 will be administered through non-occlusive intracoronary infusion via 3 vessels. The Cedars-Sinai Medical Center received approval in April 2013 to conduct this trial. In November 2015, Capricor presented positive results of the DYNAMIC trial at the 88th Annual Scientific Sessions of the American Heart Association (AHA - 2015). The results demonstrated that CAP 1002 was safe with no significant adverse cardiac effects at one month or at six months post infusion in patients with dilated cardiomyopathy. The data at six months as well as 12 months also demonstrated preliminary efficacy signal in various parameters including, subjective well-being, exercise capacity, ejection fraction and ventricular volumes      .
Duchenne muscular dystrophy (DMD)
In May 2020, Capricor Therapeutics reported that the company has requested an End-of-Phase 2 meeting with FDA to discuss next steps and a pathway to approval of a Biologics License Application for CAP 1002 in DMD  .
As of September 2019, Capricor Therapeutics completed the Type B End-of-phase II meeting with the US FDA and discussed data from the interim analysis of the phase II HOPE-2 trial [see below]. The final minutes from the meeting are awaited. Capricor Therapeutics plans to provide an update regarding the guidance received from the US FDA in Q4 2019 and plans to discuss additional data from the trial with the US FDA when available. An approval for the meeting was granted earlier in the same month  .
Capricor met the US FDA in December 2018, to discuss clinical trial design of HOPE-2 trial, surrogate or intermediate endpoints and manufacturing processes for CAP 1002. Following the discussion, the FDA advised Capricor to request an end of phase meeting to determine if HOPE-2 could serve as the registration study. The FDA also suggested to use performance of the upper limb (PUL) 2.0 mid-level test as the primary efficacy endpoint for HOPE-2  . The meeting was a part of expedited review process under Regenerative Medicine Advanced Therapy (RMAT)designation  . In February 2018, the US FDA had granted CAP 1002 Regenerative Medicine Advanced Therapy designation (RMAT) to CAP 1002 for Duchenne muscular dystrophy, based on results from the HOPE-Duchenne trial [see below]. The FDA Office of Tissues and Advanced Therapies also stated that the FDA would work with Capricor and provide guidance on subsequent development activities of CAP 1002  .
The US FDA, in July 2017, granted a Rare Pediatric Disease Designation to CAP 1002 for treatment of DMD  .
In April 2015, CAP 1002 was granted orphan drug designation by the US FDA for the treatment of Duchenne muscular dystrophy associated cardiomyopathy  .
In April 2020, Capricor Therapeutics completed the phase II HOPE-2 trial that evaluated the efficacy and safety of CAP 1002, in patients with Duchenne muscular dystrophy (CAP-1002-DMD-02; NCT03406780). The randomised, double-blind, placebo-controlled trial was initiated in April 2018, and enrolled 18 patients in the US. The company released the data from the trial in May 2020. Earlier, in July 2019, Capricor Therapeutics announced that its independent Data and Safety Monitoring Board (DSMB) completed a safety assessment and futility analysis review of the phase II HOPE-2 trial and recommended the continuation of the trial. In January 2019, the company lifted the voluntary hold on dosing that was put in December 2018, following a serious adverse event occurring in the form of anaphylaxis in a patient. To prevent future events, Capricor initiated a pre-medication strategy and is supported by the Data and Safety Monitoring Board and HOPE-2 clinical trial steering committee. In November 2017, the US FDA approved Capricor's IND application to initiate the study in Duchenne muscular dystrophy. In October 2019, Capricor Therapeutics released six-month interim data for the trial              .
In September 2017, Capricor Therapeutics completed the phase I/II HOPE-DUCHENNE (Halt cardiomyOPathy progrEssion in Duchenne) trial that evaluated the safety and tolerability of CAP 1002, in patients with cardiomyopathy secondary to Duchenne muscular dystrophy (HOPE-1; NCT02485938; CAP-1002-DMD-01). The open label trial was initiated in August 2015, and enrolled 25 patients in the US. Patients received CAP 1002 in the three main coronary arteries, to enable broad delivery across the myocardium. In June 2015, the US FDA cleared Capricor's IND application for development of CAP 1002 for the treatment of Duchenne muscular dystrophy-related cardiomyopathy. In April 2017, Capricor Therapeutics presented a top-line six-month data from the study. Based on the data, the company submitted an FDA meeting request to discuss these results and will apply for Regenerative Medicine Advanced Therapy (RMAT) designation for CAP 1002. In October 2017, the company released data demonstrating patients in advanced stages of the disease experienced meaningful improvements in cardiac and upper limb function after a single dose of CAP 1002. Updated results from the trial were presented at the 90th Annual Scientific Sessions of the American Heart Association (AHA-2017). The trial was partly funded by the California Institute for Regenerative Medicine. In January 2019, results, showing improvement in cardiac muscle function and reduction in cardiac scarring that were statistically-significant and sustained improvement of skeletal muscle functions in patients with duchenne muscular dystrophy, were published in the Journal of Neurology. In May 2020, Capricor Therapeutics released therapeutics and safety data form a phase I/II trial                        .
In April 2018, Capricor Therapeutics released preclinical results which demonstrated that CAP 1002 yields an increase in exercise performance in a disease model of Duchenne muscular dystrophy  .
In preclinical studies conducted in mouse models of DMD, intravenous CAP 1002 was shown to increase both exercise capacity and diaphragm function. The drug predominantly distributed to the lungs after injection and was cleared within three weeks. Dosing of more than 2.5 times the human equivalent dose proposed for the upcoming HOPE-2 trial was observed to be safe in these studies. The cardiosphere-derived cells (CDCs) improved cardiac muscle function, walking abilities and survival in a mouse model of duchenne muscular dystrophy. CAP 1002 stimulated tissue repair and regeneration, helped in reducing inflammation, which then enabled new healthy muscle to form, in the mouse model of duchenne muscular dystrophy. Additionally, the CDCs improved muscle physiology and showed strong immunomodulatory activity, in a mouse model of DMD    .
Positive preclinical data from a murine model of DMD were presented in November 2014 at the 87th Annual Scientific Sessions of the American Heart Association (AHA-2014).
In February 2016, the company revealed that CAP 1002 demonstrated positive efficacy in mouse preclinical models of Duchenne muscular dystrophy  .
In May 2016, Capricor announced that it has received approval for a grant award of $US3.4 million approx. from California Institute for Regenerative Medicine, to support the HOPE-Duchenne trial  .
In March 2016, Capricor received a grant of approximately $US3.38 millions from California Institute for Regenerative Medicine (CIRM) to support the development of phase I/II HOPE-Duchenne trial. The grant was awarded under the CIRM 2.0 program  .
In January 2015, Cure Duchenne Ventures invested $US1 million in Capricor Therapeutics to support a phase I/II trial in patients with heart disease associated with DMD  .
In January 2015, Capricor entered into a definitive agreement with H.C. Wainwright & Co and SC&H Capital for the sale of $US17 million of the company's common stock. The net proceeds will be used to fund the ALLSTAR and DYNAMIC trials of the product for the treatment of cardiovascular disorders. The proceeds will also be used to fund the clinical programme of CAP 002 for the treatment of Duchenne muscular dystrophy associated cardiomyopathy   .