On 11/16/09, Cytori Therapeutics (NASDAQ: CYTX) completed enrollment in a 70-patient, international breast cancer reconstruction study, RESTORE 2. The study is evaluating the use of cell-enriched fat grafting to restore functional and cosmetic deformities in women who have undergone partial mastectomy for early breast cancer. Interim data on the first 32 patients who have reached the six-month follow-up will be presented as a poster at the San Antonio Breast Cancer Symposium on 12/12/0 at 7am (CT) by Mrs. Eva Weiler-Mithoff, MD, lead investigator at the Glasgow Royal Infirmary.[More...]

In the area of heart disease, Cytori Therapeutics (NASDAQ: CYTX) is sponsoring two European clinical trials that evaluate the use of adipose-derived stem and regenerative cells (ADRCs) to treat acute myocardial infarction (MI, heart attack) and chronic myocardial ischemia (a severe form of coronary artery disease) with modes of action that include would remodeling, neo-angiogenesis (new blood vessel formation), anti-apoptosis (preventing the process of programmed cell death), immune modulation, and beneficial signaling mechanisms between cells.

 

Cytori is a leading global innovator in the emerging field of regenerative medicine using adipose (fat) tissue as a rich source of adult stem cells capable of differentiating into a variety of cell types. The Company develops and markets cell banking (StemSource), therapeutic, and cosmetic medicine applications for its Celution System, which enables real-time, point-of-care regenerative cell therapy applications by harvesting and processing a small amount of patient-derived fat tissue in about one hour to harvest the adipose-derived stem and regenerative cells (ADRCs) with key corporate partners that include GE Healthcare (NYSE: GE), Olympus Corp. (TYO: 7733) (OTC: OCPNY.PK), and Green Hospital Supply (TYO: 3360).

Data from an investigator-initiated (Dr. Yamamoto, Nagoya University) study evaluating ADRCs for the treatment of stress urinary continence (SUI) may be presented at the 7th Annual Meeting of the International Federation for Adipose Therapeutics and Science (IFATs 2009, October 15-17 in Korea). Cytori expects to receive more details on this data / presentation in the next few weeks, including the study abstract.

 

On 9/22/09, Dr. Francisco Fernandez-Aviles presented at the 21st Annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in San Francisco in a session entitled, “Update on Adipose Cells for Chronic Ischemia.” While both of Cytori’s heart trials are still blinded, the Company is especially encouraged by a distinct separation emerging in the heart attack / APOLLO trial, suggesting the potential for an innovative approach that actually repairs damaged heart tissue based on preliminary results outlined below. Cytori is more definitive on the timeline for APOLLO results being released at an appropriate medical conference during 1Q10 while the chronic ischemia trial / PRECISE timeline is remains at 1H09.

 

ADRCs have the ability to produce growth factors and differentiate into cardiac muscle and endothelial (blood vessel linings) cells. The abilities of fat-derived ADRCs are similar to bone marrow-derived stem cells with advantages that include easier access (as most individuals have a least a little fat to spare), a more abundant population of relevant regenerative cells in fat (e.g. about 45X more stem and progenitor cells obtained from 100mL of fat tissue compared to a 40mL bone marrow aspirate), and the ability to perform procedures in real-time at the point-of-care (including fat extraction and processing with the Celution System with no requirement for cell cultures).

 

Safety data obtained thus far from both the APOLLO and PRECISE trials shows that liposuction has been well tolerated in both patients with acute heart attacks and chronic / advanced heart failure and cell infusion also revealed no safety concerns when administered to patients within 24 hours of an acute MI. In addition, no arrhythmias were detected and the process of fat extraction and processing can be performed in a cardiac catheterization lab with no clean room or GMP-certified facilities required. Furthermore, only one cardiac-related death has occurred in the PRECISE trial as compared to a 20% expected mortality rate for this chronic heart ischemia patient population.

 

An interim analysis of the first five patients with acute ST-elevation MI in the APOLLO trial at a six-month follow-up revealed an average decrease of 46.4% in MI size with just one patient (+13.1%) showing an increase with the other four experienced decreases of 18.5%, 34.2%, 40.2%, and 92.6%. This data was presented by Eric Duckers, MD, PhD, FESC, in May at EuroPCR 2009 in a case review session entitled, “Mesenchymal stromal cells for cardiac regeneration.”

 

The PDF report for the data summarized in the preceding paragraphs is available at the BioMedReports.com research section, entitled, “Cytori APOLLO / PRECISE Heart Trials,” in addition to other medical / scientific reports on the breast reconstruction trial (RESTORE I) and an overview of stem cell heart research. In addition, it should be noted that the APOLLO study was halted prematurely at 14 patients based on the positive preliminary data with 12 of the subjects completing their six-month follow-up and the two remaining patients expected to complete follow-up in November.

 

The APOLLO trial is a first-in-man study evaluating the safety / effectiveness of intra-coronary administration of ADRCs in patients with acute MIs while the PRECISE study involves the intra-myocardial delivery of ADRCs in patients with chronic angina that is not responsive to conventional treatments. In addition, preliminary results from RESTORE II (ADRCs used for breast reconstruction following lumpectomy procedures) will be presented in less than three months at the San Antonio Breast Cancer Symposium (December 9-13), as outlined in my update article from mid-September, along with more details that are expected in early 2010 on the FDA medical device marketing clearance route and timeline for the Celution System.

 

More information for the APOLLO trial is available at the ClinicalTrials.gov website (NCT00442806) as enrollment for this study has been completed and patient follow-up is ongoing. In this clinical trial, a patient’s own fat-derived stem cells are extracted, processed by the Celution System, and re-injected through the coronary artery within 24 hours of experiencing heart attack symptoms. The last patient enrolled in the study is expected to finish study participation by April 2012; however, the primary outcome data from six-month follow-up for all patients is expected during 1Q10.

 

The PRECISE trial is also listed at the Clinical Trials.gov website (NCT00426868) with patient enrollment completed and follow-up is ongoing with six-month follow-up data expected during 1H10 and the last patient expected to complete study participation by April 2012. In this study, a patient’s own fat-derived stem cells are extracted, processed by the Celution System, and re-administered to injured and / or oxygen-deprived areas of the heart through a catheter.

 

It is also important to note that in addition to 120 patents and patent applications, Cytori has three distinct advantages over smaller competitors such as Tissue Genesis / Bioheart (OTC: BHRT.OB) related to commercialization barriers for new entrants in the regenerative medicine space. The first is the Olympus Joint Venture (established in 2005 with over $60 million invested by Olympus) for medical device manufacturing expertise, an established brand, and service / support functions. The second advantage is distribution partners that include GE Healthcare and Green Hospital Supply.

 

In addition, I received the following feedback from the Company on a practical note that Cytori’s sales force has not seen a competitor device in the field nor have they come up against one in a prospective sale allowing for the continued establishment of Celution System installations devoid of competition for patient-derived, adipose-based cell therapies. In addition, the high capital requirements to optimize commercial-scale manufacturing and device performance to compete with the Celution System’s cell yield, output, volume capacity, viability, and reagents suggest that a major corporate partner(s) would be required to create a competitor for Cytori.

 

Cytori has established a fiscal year 2009 revenue goal of $10 million (representing an increase of more than 2X the previous year) and a 50% reduction in the cash operating loss (with a targeted cash burn rate of $1.2 million during 2H09). The Company has approximately 36.8 million shares outstanding with $16.4 million in pro-forma cash and $1.5 million in accounts receivable as of mid-year. In addition, the equity agreement with Seaside 88, LP, announced in June provides committed financing for the purchase of up to 7.15 million shares of common stock that could address Cytori’s funding needs through the end of 2010 through a series of 26 installments of 275,000 shares each on a volume-weighted-average price basis (at a minimum price of $2.50 per share and discounted 13%).

 

Click on the following link for a five-minute YouTube video which summarizes the nine steps of preparation and processing for Cytori’s Celution System (please note that the video slides and text captions appear in English even though the title is not). In addition, the stock research section of BioMedReports.com has recently been updated to include seven new files for CYTX and the use of ADRCs, including the most recent corporate presentation and six medical / scientific publications. Click here to visit Cytori’s corporate profile page at OneMedPlace, which also includes a video interview with CEO Christopher Calhoun that is now available on YouTube.

 

The next 3-6 months have the potential to be transformational for Cytori with pending data on breast reconstruction (RESTORE II) and the two heart trials (APOLLO, PRECISE) serving as catalysts for increased market adoption and sales in Europe as reimbursement and plastic surgeon acceptance of the Celution System occurs. Also, clarity is expected in early 2010 on the Company’s medical device regulatory strategy with the FDA for the Celution System and the committed equity financing provides a funding runway that could extend through the end of 2010, which removes a major distraction for Cytori and allows it to focus on core business / R&D objectives with a full slate of clinical and regulatory catalysts expected in the next 3-6 months.

 

Disclosure: Long CYTX. See my full disclaimer at MikeHavRx.com (bottom of any page).

On 9/24/09, DNDN announced plans to file an amendment to its existing BLA seeking FDA approval in mid-November for Provenge with a possible decision by the Agency likely to occur around mid-2010. The Company will have the manufacturing capacity to generate possible sales of $60-125 million during 2H10 until full capacity is achieved in late 2011.

On 9/24/09, Chelsea Therapeutics (NASDAQ: CHTP) announced top-line results from Study 302, the first of its two Phase 3 trials of Droxidopa for the treatment of symptomatic neurogenic orthostatic hypotension (NOH). While Study 302 demonstrated that Droxidopa showed a strong symptomatic benefit during the open-label dose titration and run-in phase of the trial, a preliminary review of the data indicates it did not demonstrate a statistically significant improvement relative to placebo, as measured by the mean score of Item 1 (dizziness or light-headedness) of the Orthostatic Hypotension Symptom Assessment (OHSA) during the double-blind phase of trial, the study's primary endpoint. Droxidopa was safe and well tolerated, with no significant related adverse events reported.

Another Phase 3 trial, Study 301, was previously reviewed by the U.S. Food and Drug Administration (FDA) and awarded a Special Protocol Assessment (SPA) in February 2008. In addition to the SPA, the FDA has awarded Chelsea Fast Track designation for its pivotal program in NOH.

On 9/24/09, Cephalon (NASDAQ: CEPH) announced that the FDA granted a priority (six-month) review for its supplemental New Drug Application (sNDA) for NUVIGIL (armodafinil) Tablets [C-IV], which was filed in June of this year. The FDA decision on approval of NUVIGIL as a treatment for improving wakefulness in patients with excessive sleepiness associated with jet lag disorder due to eastbound travel is expected by 12/29/09 and there is currently no FDA-approved treatment for this indication.

On 9/24/09, OraSure Technologies (NASDAQ: OSUR) announced that it has been awarded a 36-month contract for its OraQuick ADVANCE(R) Rapid HIV-1/2 Antibody Test with Premier Purchasing Partners, L.P., that is effective 11/1/09 and provides Premier's more than 2,200 member hospitals with pre-negotiated pricing and terms for the purchase of OraSure’s test, which is the first and only FDA-approved and CLIA-waived rapid point-of-care test that can detect antibodies to both HIV-1 and HIV-2 in 20 minutes, using oral fluid, finger-stick or venipuncture whole blood or plasma specimens. Additionally, the OraQuick ADVANCE(R) test is the only rapid HIV test offered through Premier's ASCEND(TM) (Accelerated Supply Chain Endeavor) program, a group purchasing program designed to help participants achieve and sustain rapid improvements in supply chain performance. Currently, more than 90 participants representing approximately $2.7 billion in supply chain purchasing volume and close to 24,000 hospital beds are collaborating to share best practices in supply chain efficiency as a part of the program.

On 9/24/09, Genzyme (NASDAQ: GENZ) announced that its randomized Phase 3 clinical trial investigating Campath (alemtuzumab) in combination with Fludara (fludarabine phosphate) in relapsed or refractory chronic lymphocytic leukemia (CLL) patients met its primary endpoint by demonstrating a significant improvement in progression free survival (PFS). Study results from this interim analysis are expected to be submitted to the American Society of Hematology meeting held in December.

GENZ stated that, pending approval, the FluCAM dosing regimen used in the Phase 3 trial will extend the use of Campath by giving physicians an important alternative treatment regimen for their patients with progressive disease. In the CAM314 trial, patients in the FluCAM arm had lower total exposure to Campath and Fludara when dosed in combination, as compared to the labeled, single-agent dosing regimen of each drug for the treatment of CLL.

Based on the study’s positive findings, Genzyme intends to seek regulatory approval in the United States, European Union, and other countries to further broaden the Campath label to include the use of this combination regimen. If the expanded label is granted, Campath, marketed as MabCampath® in Europe, would be the first humanized monoclonal antibody approved as both a single agent and in combination therapy for the treatment of CLL.

In collaboration with NIH scientists, Dr. Kovach / Lixte Biotech (OTC: LIXT.OB) have a new publication (Cell Cycle 8:20, 1-4; October 15, 2009) which is entitled, “Enhancement of cancer chemotherapy by simultaneously altering cell cycle progression and DNA-damage defenses through global modification of the serine/threonine phospho-proteome.” To summarize, Lixte’s lead compound has demonstrated positive preclinical results and has the potential to greatly enhance the cancer killing effects as part of combination treatment with chemotherapy drugs that target DNA as their mode of action such as temozolomide and doxorubicin. Lixte’s lead compound has a counter-intuitive mode of action that involves speeding up the cell cycle / DNA replication process of cancer cells despite the presence of chemo-induced DNA damage.

These cancer cells would otherwise lie dormant and repair the DNA damage caused by drugs such as Temodar, but in combination with Lixte’s compound, the cancer cells speed through the cell cycle / replication process to their demise. The authors of this article conclude that (1) the absence of toxicity in preclinical / animal model studies suggests that specific mutations in the signaling pathways regulating the cell cycle in cancer cells make them more vulnerable to this mode of action as compared to normal cells and (2) the mode of action of Lixte’s compound (global modulation of the serine-threonine phospho-proteome) may represent a general method of enhancing the anti-cancer effects of cytotoxic chemotherapy drugs by exploiting molecular defects in cell cycle regulation for targeted killing of cancer cells.

As a follow-up to my article earlier this week, Cytori’s (NASDAQ: CYTX) Cardiac Celution: Encouraging Interim Results, a 31-page PDF is now available at the BioMedReports.com research section in the medical / scientific reports section for a presentation earlier this week by Dr. Francisco Fernandez-Aviles (who kindly sent me the file today) at the 21st Annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in San Francisco in a session entitled, “Update on Adipose Cells for Chronic Ischemia.”

 

Disclosure: Long CYTX.

See my full disclaimer at MikeHavRx.com (bottom of any page).