Cytori Cell Therapy™ is for investigational use in the United States.
Cytori Cell Therapy™:
Cytori Therapeutics, Inc. develops cellular therapies designed to repair injured tissue, preserve function, improve quality of life, and modify disease progression. Known collectively as Cytori Cell Therapy™, these cellular therapeutics harness the unique attributes of living cells that are prepared from a patient’s own adipose tissue, known as Adipose-Derived Regenerative Cells (ADRCs).
Cytori develops nanomedicines using liposomal encapsulation technology designed to reduce toxicity while retaining the efficacy of both existing agents and novel compounds. For oncology patients, the size and composition of liposomal-encapsulated products are designed such that the chemotherapeutic agent can be delivered more selectively to the tumor1,2. Clinical trials have demonstrated that encapsulation can protect organs such as the heart from the toxic effects of the chemotherapy agents such as doxorubicin leading to a safety and efficacy profile that is superior to that of the non-encapsulated drug.2
Cytori exclusively uses human adipose tissue as the raw material to manufacture cellular therapies.
Why use adipose?
Human adipose tissue (fat tissue) is a unique reservoir of multiple types of cells that can contribute to the healing process. Cytori has developed technology to derive a heterogeneous cell population from adipose, also referred to as Adipose-Derived Regenerative Cells, or ADRCs. ADRCs can be used to create a number of cellular therapeutics. Since Cytori uses ADRCs from a patient’s own body, treatment with these cells avoid common transplantation issues such as cell rejection or disease transmission, and do not require anti-rejection or immunosuppression drugs.
Cytori is a specialty therapeutics company focused on bringing to market cell therapies and nanomedicines that address unmet medical needs. Our development pipeline is founded upon promising research data generated in a variety of preclinical studies, investigator driven studies, and Cytori-sponsored clinical trials.
Scleroderma Associated Hand Dysfunction
Cutaneous Radiation & Thermal Injury
Scleroderma Associated Hand Dysfunction
Cutaneous Radiation & Thermal Injury
* for European and Japanese studies: Investigator-initiated Study
Cytori Therapeutics’ clinical development program consists of rigorous, well-designed, controlled studies targeted to clinical indications with significant medical needs inadequately addressed by currently available therapeutic options.
Cytori Cell Therapy is comprised of ADRCs and specifically adapted to individual indications or clinical situations. For example, formulation HABEO™” has been developed for the treatment of the hand dysfunction associated with the autoimmune disease scleroderma.
The STAR Trial is a randomized, double blind, placebo-controlled, Phase III pivotal clinical trial of 80 patients with impaired hand function from scleroderma in up to 20 US sites. The trial is evaluating the one-year safety and efficacy of a single administration of Cytori Cell Therapy: HABEO™ in patients with scleroderma affecting the hands. More than 90 percent of scleroderma patients have hand involvement, which is typically progressive with substantial pain, blood flow changes, and dysfunction. The primary endpoint of the study is the Cochin Hand Function Score—a validated measure of hand function. Other key efficacy endpoints include assessments of Raynaud ’s phenomenon, and other objective measures of hand function and digital ulcers. After all patients have completed 48 weeks of follow up, patients in the placebo group will be eligible for crossover to the active arm of the trial. Completion of enrollment is anticipated in June 2016.
This trial is based on the previously published trial, SCLERADEC I, conducted at Hȏpital de la Conception in France. SCLERADEC I reported significant improvement in hand function, pain, and Raynaud’s severity in patients with scleroderma affecting the hands.1,2,5 Cytori supported this trial in the form of devices, consumables, and training. Cytori is also providing support for SCLERADEC II, a multi-center, controlled study in France.
Cytori has completed ACT-OA, a US IDE Phase IIA/B clinical trial of the ECCO-50 therapeutic in 94 patients with osteoarthritis affecting the knees. The study is examining the safety and efficacy (symptom relief, function, and activity level) of ECCO-50 at multiple time points through 48 weeks. Full data should be available in late 2016.
THERMAL BURN AND RADIATION INJURY – BARDA CONTRACT
In December 2012 Cytori was awarded a research and development contract from the Biomedical Advanced Research and Development Authority (BARDA), a unit within the US Department of Health and Human Services. This contract funds the development of Cytori Cell Therapy™ as a medical countermeasure for thermal burn injury including burns that are complicated by radiation exposure. In 2014, upon achievement of specified development milestones by Cytori, BARDA executed contract Option 1 which funded the second phase of the project. Upon IDE approval by the FDA, BARDA anticipates exercising Option 2 funding which will cover costs associated with execution of a pilot clinical trial.
Cytori has agreed to provide partial support to a planned Japanese investigator/government sponsored trial of Cytori Cell Therapy for male urinary incontinence following radical prostatectomy. This trial is based on a previously published2 feasibility trial conducted at Nagoya University in Japan. This trial demonstrated improvements in leakage, urethral closure, and patient quality-of-life assessment in men with urinary incontinence following radical prostatectomy for prostate cancer. The primary funding and support of the trial is from the Japanese Ministry of Health, Labor and Welfare and Nagoya University.
By providing access to Cytori Cell Therapy processing technology in markets where it has class I or CE Mark approval, the Celution® System has become an important research and development tool for physicians. This enables them to study the potential of our technology in Institutional Review Board (IRB) and Medical Ethics Committee (MEC)-approved studies. A number of investigator-led trials have been completed, are in process, for a range of conditions and applications, including the following:
- Anterior cruciate ligament repair
- Bone repair
- Burn scar
- Chronic wounds
- Critical limb ischemia
- Cryptoglandular and Crohn’s Fistulae
- Erectile Dysfunction
- Meniscal Repair
- Stress urinary incontinence
- Scleroderma hand disease
- Vocal cord repair
Other Clinical Trials
PRECISE was a 27 patient safety and feasibility study in Europe designed to evaluate the use of Cytori Cell Therapy in patients with chronic myocardial ischemia. Data from the PRECISE trial indicated the feasibility of obtaining and delivering Cytori Cell Therapy to patients with significant heart disease. The data provided early indications of efficacy that provided the rationale for the ATHENA trials in the US.
The ATHENA I and II trials are multi-center, randomized, double-blind safety and feasibility trials to investigate the use of Cytori Cell Therapy in patients with heart failure due to ischemic heart disease. The trials were originally planned to enroll 45 patients each and examine two dosages of Cytori Cell Therapy.
The trials incorporated several endpoints, including peak oxygen consumption, perfusion defects, heart failure symptoms, health-related quality of life, left ventricle end-systolic and diastolic volume, and left ventricular ejection fraction at six and 12 months. Enrollment was truncated at 31 patients in 2014 due to a prolonged trial delay in 2014; however, data will be available for review in mid-2016.
ACUTE MYOCARDIAL INFARCTION
The APOLLO Trial was a 14-patient study in Europe designed to assess the safety and feasibility of Cytori Cell Therapy in patients with ST-elevation myocardial infarction (STEMI). Enrollment and 36-month patient follow up is complete. The study demonstrated the feasibility of intracoronary injections of Cytori Cell Therapy in STEMI patients and provided the rationale for the ADVANCE trial.
The ADVANCE Trial was a 23 patient randomized, placebo-controlled, double-blind European trial at four centers and was a follow up to APOLLO. The trial evaluated administration of cell therapy in patients with STEMI. All available data supported the current known safety profile for Cytori Cell Therapy.
The RESTORE-2 study was a Phase IV (post-market) European study that evaluated Cytori Cell Therapy for breast deformities post segmental breast resection (lumpectomy) with or without radiation therapy. This prospective, single-arm, open-label, multi-center study enrolled 71 patients with defects ranging from 25-150 mL. The procedure was shown to be safe and well tolerated. The data reported patient and investigator satisfaction (75% and 85% respectively) following cell-enriched fat grafting to treat breast defects post-breast conservation therapy.4
- 1 Gabizon A, Shmeeda H, and Barenholz Y (2003) “Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies” Clin Pharmacokinet. 42(5):419-36
- 2 Rafiyath et al. 2012 “Comparison of safety and toxicity of liposomal doxorubicin vs. conventional anthracyclines: a meta-analysis” Exp Hematol Oncol 1:10-19
ATI-0918 is Cytori’s lead nanomedicine product, a generic liposomal formulation of doxorubicin hydrochloride. Liposomal doxorubicin has been approved by the FDA and the European Medicines Agency (EMA) for several years. The approved drugs are now off-patent. This creates an expedited path for regulatory approval of generic formulations in which clinical trials are targeted at showing “bioequivalence” which means that the drug levels in the blood and tissue following injection of ATI-0918 must be equivalent (using FDA/EMA-specified bioequivalence criteria) to the levels seen when the approved product is injected. Bioequivalence studies typically require only one clinical trial as opposed to the conventional Phase I, Phase II, and Phase III pathway required for new drugs. Bioequivalence of ATI-0918 and the reference listed drug in Europe, (Caelyx®), has already been demonstrated in a clinical trial. Cytori is now preparing for submission for approval by the EMA. If granted, this approval will allow marketing of ATI-0918 for use in breast cancer and ovarian cancer with the possibility of extending this to both multiple myeloma and Kaposi’s sarcoma. Bioequivalence with the FDA-approved reference listed drug (Lipodox®) in the USA has not yet been performed.
ATI-1123, a liposomal formulation of docetaxel, is being developed as a next-generation version of the currently approved product. Docetaxel is approved in the USA for the treatment of a number of cancers including breast cancer, head and neck cancer, stomach cancer, prostate cancer and non small-cell lung cancer. Use of docetaxel is associated with several side effects including injury to the bone marrow. Cytori believes that by encapsulating docetaxel in a liposome, ATI-1123 may reduce these side effects. A 29 patient Phase I trial has been completed and published6. This published data suggests that the toxicity may be less than that reported for non-encapsulated docetaxel. This will need to be confirmed in larger Phase II and Phase III clinical trials.
- 6. Mahalingam D, Nemunaitis JJ, Malik L, et al. Phase I study of intravenously administered ATI-1123, a liposomal docetaxel formulation in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Dec;74(6):1241-50. doi: 10.1007/s00280-014-2602-x. Epub 2014 Oct 11.